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  • 1.
    Bejarano, J.
    et al.
    Advanced Center for Chronic Diseases (ACCDiS), Facultad Ciencias Químicas y Farmaceuticas, Universidad de Chile, Santiago, Chile.
    Navarro-Marquez, M.
    Advanced Center for Chronic Diseases (ACCDiS), Facultad Ciencias Químicas y Farmaceuticas, Universidad de Chile, Santiago, Chile.
    Morales-Zavala, F.
    Advanced Center for Chronic Diseases (ACCDiS), Facultad Ciencias Químicas y Farmaceuticas, Universidad de Chile, Santiago, Chile.
    Morales, Javier O.
    Luleå University of Technology, Department of Health Sciences, Medical Science. Advanced Center for Chronic Diseases (ACCDiS), Facultad Ciencias Químicas y Farmaceuticas, Universidad de Chile, Santiago, Chile; Departamento de Ciencias y Tecnología Farmacéuticas, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago, Chile.
    Garcia-Carvajal, I.
    Advanced Center for Chronic Diseases (ACCDiS), Facultad Ciencias Químicas y Farmaceuticas, Universidad de Chile, Santiago, Chile.
    Araya-Fuentes, E.
    Advanced Center for Chronic Diseases (ACCDiS), Facultad Ciencias Químicas y Farmaceuticas, Universidad de Chile, Santiago, Chile; Departamento de Ciencias Quimicas, Facultad de Ciencias Exactas, Universidad Andres Bello, Santiago, Chile.
    Flores, Y.
    Advanced Center for Chronic Diseases (ACCDiS), Facultad Ciencias Químicas y Farmaceuticas, Universidad de Chile, Santiago, Chile.
    Verdejo, H.E.
    Advanced Center for Chronic Diseases (ACCDiS), División de Enfermedades Cardiovasculares, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.
    Castro, P.F.
    Advanced Center for Chronic Diseases (ACCDiS), División de Enfermedades Cardiovasculares, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.
    Lavandero, S.
    Advanced Center for Chronic Diseases (ACCDiS), Facultad Ciencias Químicas y Farmaceuticas, Universidad de Chile, Santiago, Chile; Advanced Center for Chronic Diseases (ACCDiS), Centro de Estudios en Ejercicio, Metabolismo y Cáncer (CEMC), Instituto de Ciencias Biomedicas (ICBM), Facultad de Medicina, Universidad de Chile, Santiago, Chile. Department of Internal Medicine (Cardiology Division), University of Texas Southwestern Medical Center, Dallas, TX, United States.
    Kogan, M.J.
    Advanced Center for Chronic Diseases (ACCDiS), Facultad Ciencias Químicas y Farmaceuticas, Universidad de Chile, Santiago, Chile; Departamento de Química Farmacológica y Toxicológica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Chile.
    Nanoparticles for diagnosis and therapy of atherosclerosis and myocardial infarction: evolution toward prospective theranostic approaches2018In: Theranostics, ISSN 1838-7640, E-ISSN 1838-7640, Vol. 8, no 17, p. 4710-4732Article in journal (Refereed)
    Abstract [en]

    Cardiovascular diseases are the leading cause of death worldwide. Despite preventive efforts, early detection of atherosclerosis, the common pathophysiological mechanism underlying cardiovascular diseases remains elusive, and overt coronary artery disease or myocardial infarction is often the first clinical manifestation. Nanoparticles represent a novel strategy for prevention, diagnosis, and treatment of atherosclerosis, and new multifunctional nanoparticles with combined diagnostic and therapeutic capacities hold the promise for theranostic approaches to this disease. This review focuses on the development of nanosystems for therapy and diagnosis of subclinical atherosclerosis, coronary artery disease, and myocardial infarction and the evolution of nanosystems as theranostic tools. We also discuss the use of nanoparticles in noninvasive imaging, targeted drug delivery, photothermal therapies together with the challenges faced by nanosystems during clinical translation.

  • 2.
    Catalan-Figueroa, Johanna
    et al.
    Department of Pharmaceutical Science and Technology, School of Chemical and Pharmaceutical Sciences, University of Chile, Santiago, Chile. Department of Biochemistry, School of Chemical and Pharmaceutical Sciences, University of Chile, Santiago, Chile. Centro de Nanotecnología Aplicada, Universidad Mayor, Santiago, Chile.
    Boisset, Constanza B
    Department of Pharmaceutical Science and Technology, School of Chemical and Pharmaceutical Sciences, University of Chile, Santiago, Chile.
    Jara, Miguel O
    Department of Pharmaceutical Science and Technology, School of Chemical and Pharmaceutical Sciences, University of Chile, Santiago, Chile.
    Flores, Mario E
    Instituto de Ciencias Químicas, Facultad de Ciencias, Universidad Austral de Chile, Valdivia, Chile.
    Moreno-Villoslada, Ignacio
    Instituto de Ciencias Químicas, Facultad de Ciencias, Universidad Austral de Chile, Valdivia, Chile.
    Fiedler, Jenny L
    Centro de Nanotecnología Aplicada, Universidad Mayor, Santiago, Chile.
    Morales, Javier O.
    Luleå University of Technology, Department of Health Sciences, Medical Science. Department of Pharmaceutical Science and Technology, School of Chemical and Pharmaceutical Sciences, University of Chile, Santiago, Chile. Advanced Center for Chronic Diseases (ACCDiS), Santiago, Chile.
    A mechanistic approach for the optimization of loperamide loaded nanocarriers characterization: Diafiltration and mathematical modeling advantages2018In: European Journal of Pharmaceutical Sciences, ISSN 0928-0987, E-ISSN 1879-0720, Vol. 125, p. 215-222Article in journal (Refereed)
    Abstract [en]

    Oral bioavailability of loperamide is restricted by its limited absorption in the gastrointestinal tract due to its poor aqueous solubility and its P-glycoprotein (Pgp) substrate characteristic. In addition, ammonium methacrylate copolymers have shown to have mucoadhesive properties, whereas poloxamer 188, has been suggested as a Pgp inhibitor. Thus, in this work, we evaluate conditions that affect physicochemical parameters of ammonium methacrylate/poloxamer 188-based nanocarriers loaded with loperamide hydrochloride. Nanocarriers were synthesized by nanoprecipitation, enhancing loperamide encapsulation efficiency by modifying the aqueous phase to basic pH. The isolation of the non-encapsulated drug fraction from the nanocarriers-incorporated fraction was conducted by centrifugation, ultrafiltration, vacuum filtration and diafiltration. The last method was effective in providing a deeper understanding of drug-nanocarrier loading and interactions by means of modeling the data obtained by it. Through diafiltration, it was determined an encapsulation efficiency of about 93%, from which a 38% ±6 was shown to be reversibly (thermodynamic interaction) and a 62% ±6 irreversibly (kinetic interaction) bound. Finally, release profiles were assessed through empirical and semi-empirical modeling, showing a biphasic release behavior (burst effect 11.34% and total release at 6 h = 33% ±1). Thus, encapsulation efficiency and release profile were shown to have a strong mathematical modeling-based correlation, providing the mechanistic approach presented in this article a solid support for future translational investigations.

  • 3.
    Catalan-Figueroa, Johanna
    et al.
    Department of Pharmaceutical Science and Technology, School of Chemical and Pharmaceutical Sciences, University of Chile, Santiago.
    Palma-Florez, Sujey
    Advanced Center for Chronic Diseases (ACCDiS), Santiago.
    Alvarez, Gonzalo
    Department of Pharmaceutical Science and Technology, School of Chemical and Pharmaceutical Sciences, University of Chile, Santiago.
    Fritz, Hans F.
    Department of Pharmaceutical Science and Technology, School of Chemical and Pharmaceutical Sciences, University of Chile, Santiago.
    Jara, Miguel O.
    Department of Pharmaceutical Science and Technology, School of Chemical and Pharmaceutical Sciences, University of Chile, Santiago.
    Morales, Javier O.
    Department of Pharmaceutical Science and Technology, School of Chemical and Pharmaceutical Sciences, University of Chile, 8380494, Santiago.
    Nanomedicine and nanotoxicology: The pros and cons for neurodegeneration and brain cancer2016In: Nanomedicine, ISSN 1743-5889, E-ISSN 1748-6963, Vol. 11, no 2, p. 171-187Article in journal (Refereed)
    Abstract [en]

    Current strategies for brain diseases are mostly symptomatic and noncurative. Nanotechnology has the potential to facilitate the transport of drugs across the blood-brain barrier and to enhance their pharmacokinetic profile. However, to reach clinical application, an understanding of nanoneurotoxicity in terms of oxidative stress and inflammation is required. Emerging evidence has also shown that nanoparticles have the ability to alter autophagy, which can induce inflammation and oxidative stress, or vice versa. These effects may increase neurodegenerative processes damage, but on the other hand, they may have benefits for brain cancer therapies. In this review, we emphasize how nanomaterials may induce neurotoxic effects focusing on neurodegeneration, and how these effects could be exploited toward brain cancer treatment

  • 4.
    Fritz, Hans F.
    et al.
    Department of Pharmaceutical Science and Technology, School of Chemical and Pharmaceutical Sciences, University of Chile.
    Ortiz, Andrea C.
    Department of Pharmaceutical Science and Technology, School of Chemical and Pharmaceutical Sciences, University of Chile.
    Velaga, Sitaram
    Luleå University of Technology, Department of Health Sciences, Medical Science.
    Morales, Javier O.
    Luleå University of Technology, Department of Health Sciences, Medical Science. Department of Pharmaceutical Science and Technology, School of Chemical and Pharmaceutical Sciences, University of Chile.
    Preparation of a novel lipid-core micelle using a low-energy emulsification method2018In: Drug Delivery and Translational Research, ISSN 2190-393X, E-ISSN 2190-3948 , Vol. 8, no 6, p. 1807-1814Article in journal (Refereed)
    Abstract [en]

    High-energy methods for the manufacturing of nanomedicines are widely used; however, interest in low-energy methods is increasing due to their simplicity, better control over the process, and energy-saving characteristics during upscaling. Here, we developed a novel lipid-core micelle (LCM) as a nanocarrier to encapsulate a poorly water-soluble drug, nifedipine (NFD), by hot-melt emulsification, a low-energy method. LCMs are self-assembling colloidal particles composed of a hydrophobic core and a hydrophilic shell. Hybrid materials, such as Gelucire 44/14, are thus excellent candidates for their preparation. We characterized the obtained nanocarriers for their colloidal properties, drug loading and encapsulation efficiency, liquid state, stability, and drug release. The low-energy method hot-melt emulsification was successfully adapted for the manufacturing of small and narrowly dispersed LCMs. The obtained LCMs had a small average size of ~ 11 nm and a narrow polydispersity index (PDI) of 0.228. These nanocarriers were able to increase the amount of NFD dispersible in water more than 700-fold. Due to their sustained drug release profile and the PEGylation of Gelucire 44/14, these nanocarriers represent an excellent starting point for the development of drug delivery systems designed for long circulation times and passive targeting.

  • 5.
    Jara, Miguel O.
    et al.
    Department of Pharmaceutical Science and Technology, School of Chemical and Pharmaceutical Sciences, University of Chile, Santiago, Chile.
    Catalan-Figueroa, Johanna
    Department of Pharmaceutical Science and Technology, School of Chemical and Pharmaceutical Sciences, University of Chile, Santiago, Chile.
    Landin, Mariana
    Department of Pharmacology, Pharmacy and Pharmaceutical Technology, University of Santiago, Santiago de Compostela, Spain.
    Morales, Javier O.
    Luleå University of Technology, Department of Health Sciences, Medical Science. Department of Pharmaceutical Science and Technology, School of Chemical and Pharmaceutical SciencesUniversity of Chile, Santiago, Chile. Advanced Center for Chronic Diseases (ACCDiS), Santiago, Chile.
    Finding key nanoprecipitation variables for achieving uniform polymeric nanoparticles using neurofuzzy logic technology2018In: Drug Delivery and Translational Research, ISSN 2190-393X, E-ISSN 2190-3948 , Vol. 8, no 6, p. 1797-1806Article in journal (Refereed)
    Abstract [en]

    Nanoprecipitation is a simple and fast method to produce polymeric nanoparticles (Np); however, most applications require filtration or another separation technique to isolate the nanosuspension from aggregates or polydisperse particle production. In order to avoid variability introduced by these additional steps, we report here a systematic study of the process to yield monomodal and uniform Np production with the nanoprecipitation method. To further identify key variables and their interactions, we used artificial neural networks (ANN) to investigate the multiple variables which influence the process. In this work, a polymethacrylate derivative was used for Np (NpERS) and a database with several formulations and conditions was developed for the ANN model. The resulting ANN model had a high predictability (> 70%) for NpERS characteristics measured (mean size, PDI, zeta potential, and number of particle populations). Moreover, the model identified production variables leading to polymer supersaturation, such as mixing time and turbulence, as key in achieving monomodal and uniform NpERS in one production step. Polymer concentration and type of solvent, modifiers of polymer diffusion and supersaturation, were also shown to control NpERS characteristics. The ANN study allowed the identification of key variables and their interactions and resulted in a predictive model to study the NpERS production by nanoprecipitation. In turn, we have achieved an optimized method to yield uniform NpERS which could pave way for polymeric nanoparticle production methods with potential in biological and drug delivery applications.

  • 6.
    Jullian, Carolina
    et al.
    Departamento de Química Orgánica y Fisicoquímica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile.
    Morales, Javier O.
    Departamento de Química Orgánica y Fisicoquímica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile.
    Zapata-Torres, Gerald
    Departamento de Química Inorgánica y Analítica, Facultad de de Ciencias Químicas y Farmacéuticas, Universidad de Chile.
    Aguilera, Benjamín
    Departamento de Química Inorgánica y Analítica, Facultad de de Ciencias Químicas y Farmacéuticas, Universidad de Chile.
    Rodriguez, Jorge
    Departamento de Química Inorgánica y Analítica, Facultad de de Ciencias Químicas y Farmacéuticas, Universidad de Chile.
    Arán, Vicente
    Instituto de Química Médica, CSIC.
    Olea-Azar, Claudio
    Departamento de Química Inorgánica y Analítica, Facultad de de Ciencias Químicas y Farmacéuticas, Universidad de Chile.
    Characterization, phase-solubility, and molecular modeling of inclusion complex of 5-nitroindazole derivative with cyclodextrins.2008In: Bioorganic & Medicinal Chemistry, ISSN 0968-0896, E-ISSN 1464-3391, Vol. 16, no 9, p. 5078-5084Article in journal (Refereed)
    Abstract [en]

    The slightly water-soluble 5-nitroindazole derivative (5-NI) and its inclusion with either beta-cyclodextrin (betaCD) or Heptakis (2,6-di-O-methyl)-beta-cyclodextrin (DMbetaCD) were investigated. The stoichiometric ratios and stability constants describing the extent of formation of the complexes were determined by phase-solubility measurements obtaining type-A(L) diagrams in both cases. According to the continuous variation method (Job's plot) a 1:1 stoichiometry has been proposed for the complexes. Also electrochemical studies were carried out on both CDs complexes, where the observed change in the E(PC) value for DMbetaCD indicated a lower feasibility of the nitro group reduction. The detailed spatial configuration is proposed based on two-dimensional NMR methods. These results are further interpreted using molecular modeling studies. The latter results are in good agreement with the experimental data.

  • 7.
    Montenegro-Nicolin, Miguel
    et al.
    Department of Pharmaceutical Science and Technology, School of Chemical and Pharmaceutical Sciences, University of Chile, Santiago.
    Reyes, Patricio E.
    Instituto de Salud Pública de Chile, Santiago.
    Jara, Miguel O.
    Department of Pharmaceutical Science and Technology, School of Chemical and Pharmaceutical Sciences, University of Chile, Santiago.
    Vuddanda, Parameswara Rao
    Luleå University of Technology, Department of Health Sciences, Medical Science.
    Neira-Carrillo, Andrónico
    Advanced Center for Chronic Diseases (ACCDiS), Santiago.
    Butto, Nicole
    Advanced Center for Chronic Diseases (ACCDiS, )Santiago.
    Velaga, Sitaram
    Luleå University of Technology, Department of Health Sciences, Medical Science.
    Morales, Javier O.
    Luleå University of Technology, Department of Health Sciences, Medical Science. Department of Pharmaceutical Science and Technology, School of Chemical and Pharmaceutical Sciences, University of Chile, Santiago.
    The Effect of Inkjet Printing over Polymeric Films as Potential Buccal Biologics Delivery Systems2018In: AAPS PharmSciTech, E-ISSN 1530-9932, Vol. 19, no 8, p. 3376-3387Article in journal (Refereed)
    Abstract [en]

    The buccal mucosa appears as a promissory route for biologic drug administration, and pharmaceutical films are flexible dosage forms that can be used in the buccal mucosa as drug delivery systems for either a local or systemic effect. Recently, thin films have been used as printing substrates to manufacture these dosage forms by inkjet printing. As such, it is necessary to investigate the effects of printing biologics on films as substrates in terms of their physical and mucoadhesive properties. Here, we explored solvent casting as a conventional method with two biocompatible polymers, hydroxypropyl methylcellulose, and chitosan, and we used electrospinning process as an electrospun film fabrication of polycaprolactone fibers due to its potential to elicit mucoadhesion. Lysozyme was used as biologic drug model and was formulated as a solution for printing by thermal inkjet printing. Films were characterized before and after printing by mechanical and mucoadhesive properties, surface, and ultrastructure morphology through scanning electron microscopy and solid state properties by thermal analysis. Although minor differences were detected in micrographs and thermograms in all polymeric films tested, neither mechanical nor mucoadhesive properties were affected by these differences. Thus, biologic drug printing on films was successful without affecting their mechanical or mucoadhesive properties. These results open way to explore biologics loading on buccal films by inkjet printing, and future efforts will include further in vitro and in vivo evaluations.

  • 8.
    Montenegro-Nicolini, Miguel
    et al.
    Department of Pharmaceutical Science and Technology, School of Chemical and Pharmaceutical Sciences, University of Chile.
    Miranda, Victor
    Department of Pharmaceutical Science and Technology, School of Chemical and Pharmaceutical Sciences, University of Chile, Santiago.
    Morales, Javier O.
    Department of Pharmaceutical Science and Technology, School of Chemical and Pharmaceutical Sciences, University of Chile, Santiago.
    Inkjet Printing of Proteins: an Experimental Approach2017In: AAPS Journal, E-ISSN 1550-7416, Vol. 19, no 1, p. 234-243Article in journal (Refereed)
    Abstract [en]

    Peptides and proteins represent a promissory group of molecules used by the pharmaceutical industry for drug therapy with great potential for development. However, the administration of these molecules presents a series of difficulties, making necessary the exploration of new alternatives like the buccal route of administration to improve drug therapy compliance. Although drop-on demand printers have been explored for small molecule drugs with promising results, the development of delivery systems for peptides and proteins through inkjet printing has seen little development. Therefore, the aim of this study was to assess the feasibility of using a thermal inkjet printing system for dispensing lysozyme and ribonuclease-A as model proteins. To address the absorption limitations of a potential buccal use, a permeation enhancer (sodium deoxycholate) was also studied in formulations. We found that a conventional printer successfully printed both proteins, exhibiting very high printing efficiency. Furthermore, the protein structure was not affected and minor effects were observed in the enzymatic activity after the printing process. In conclusion, we provide evidence for the usage of an inexpensive, easy to use, reliable, and reproducible thermal inkjet printing system to dispense proteins solutions for potential buccal application. Our research significantly contributes to present an alternative for manufacturing biologics delivery systems, with emphasis in buccal applications. Next steps of developments will be aimed at the use of new materials for printing, controlled release, and protection strategies for proteins and peptides

  • 9.
    Montenegro-Nicolini, Miguel
    et al.
    Department of Pharmaceutical Science and Technology, School of Chemical and Pharmaceutical Sciences, University of Chile, Santos Dumont 964, 4to piso, Of# 09, Independencia, Santiago, 8380494, Chile;Instituto de Salud Pública de Chile, Santiago, 7780050, Chile.
    Morales, Javier O.
    Department of Pharmaceutical Science and Technology, School of Chemical and Pharmaceutical Sciences, University of Chile, Santos Dumont 964, 4to piso, Of# 09, Independencia, Santiago, 8380494, Chile;Advanced Center for Chronic Diseases (ACCDiS), Santos Dumont 964, 4to piso, Of# 09, Independencia, Santiago, 8380494, Chile.
    Overview and Future Potential of Buccal Mucoadhesive Films as Drug Delivery Systems for Biologics2017In: AAPS PharmSciTech, E-ISSN 1530-9932, Vol. 18, no 1, p. 3-14Article in journal (Refereed)
    Abstract [en]

    The main route of administration for drug products is the oral route, yet biologics are initially developed as injectables due to their limited stability through the gastrointestinal tract and solubility issues. In order to avoid injections, a myriad of investigations on alternative administration routes that can bypass enzymatic degradation and the first-pass effect are found in the literature. As an alternative site for biologics absorption, the buccal route presents with a number of advantages. The buccal mucosa is a barrier, providing protection to underlying tissue, but is more permeable than other alternative routes such as the skin. Buccal films are polymeric matrices designed to be mucoadhesive properties and usually formulated with permeability enhancers to improve bioavailability. Conventionally, buccal films for biologics are manufactured by solvent casting, yet recent developments have shown the potential of hot melt extrusion, and most recently ink jet printing as promising strategies. This review aims at depicting the field of biologics-loaded mucoadhesive films as buccal drug delivery systems. In light of the literature available, the buccal epithelium is a promising route for biologics administration, which is reflected in clinical trials currently in progress, looking forward to register and commercialize the first biologic product formulated as a buccal film.

  • 10.
    Montero-Padilla, Soledad
    et al.
    Department of Pharmaceutical Science and Technology, School of Chemical and Pharmaceutical Sciences, University of Chile, 8380494, Santiago.
    Velaga, Sitaram
    Luleå University of Technology, Department of Health Sciences, Medical Science.
    Morales, Javier O.
    Department of Pharmaceutical Science and Technology, School of Chemical and Pharmaceutical Sciences, University of Chile, 8380494, Santiago.
    Buccal Dosage Forms: general Considerations for Pediatric Patients2017In: AAPS PharmSciTech, E-ISSN 1530-9932, Vol. 18, no 2, p. 273-282Article in journal (Refereed)
    Abstract [en]

    The development of an appropriate dosage form for pediatric patients needs to take into account several aspects, since adult drug biodistribution differs from that of pediatrics. In recent years, buccal administration has become an attractive route, having different dosage forms under development including tablets, lozenges, films, and solutions among others. Furthermore, the buccal epithelium can allow quick access to systemic circulation, which could be used for a rapid onset of action. For pediatric patients, dosage forms to be placed in the oral cavity have higher requirements for palatability to increase acceptance and therapy compliance. Therefore, an understanding of the excipients required and their functions and properties needs to be particularly addressed. This review is focused on the differences and requirements relevant to buccal administration for pediatric patients (compared to adults) and how novel dosage forms can be less invasive and more acceptable alternatives. 

  • 11.
    Morales, Javier O.
    Department of Pharmaceutical Science and Technology, School of Chemical and Pharmaceutical Sciences, University of Chile.
    Formulation and Delivery of Macromolecules2017In: AAPS PharmSciTech, E-ISSN 1530-9932, Vol. 18, no 1, p. 1-2Article in journal (Other academic)
  • 12.
    Morales, Javier O.
    Department of Pharmaceutical Science and Technology School of Chemical and Pharmaceutical Sciences University of Chile.
    Remington: Essentials of Pharmaceutics. By Linda Felton,Pharmaceutical Press, Gurnee, IL, 2013, 784 pages, ISBN:97808571110502015In: Drug Development and Industrial Pharmacy, ISSN 0363-9045, E-ISSN 1520-5762, Vol. 41, no 4, p. 529-Article, book review (Other academic)
  • 13.
    Morales, Javier O.
    et al.
    Luleå University of Technology, Department of Health Sciences, Medical Science. Department of Pharmaceutical Science and Technology, School of Chemical and Pharmaceutical Sciences, University of Chile, Santiago .
    Brayden, David J.
    UCD School of Veterinary Medicine and UCD Conway Institute, University College Dublin.
    Buccal delivery of small molecules and biologics: of mucoadhesive polymers, films, and nanoparticles2017In: Current opinion in pharmacology (Print), ISSN 1471-4892, E-ISSN 1471-4973, Vol. 36, p. 22-28Article in journal (Refereed)
    Abstract [en]

    Buccal delivery of macromolecules (biologics) sets a great challenge for researchers. Although several niche small molecule products have been approved as simple sprays, tablets and oral films, it is not simply a case of adapting existing technologies to biologics. Buccal delivery of insulin has reached clinical trials with two approaches: oromucosal sprays of the peptide with permeation enhancers, and embedded gold nanoparticles in a dissolvable film. However, neither of these approaches have led to FDA approvals likely due to poor efficacy, submaximal peptide loading in the dosage form, and to wide intra-subject variability in pharmacokinetics and pharmacodynamics. It is likely however that printed film designs with lower molecular weight stable biotech payloads including lipophilic glucagon-like 1 (GLP-1) agonists and macrocycles with long half-lives will generate greater efficacy than was achieved to date for insulin.

  • 14.
    Morales, Javier O.
    et al.
    Department of Pharmaceutical Science and Technology, School of Chemical and Pharmaceutical Sciences, University of Chile, Santiago.
    Fathe, Kristin R.
    Division of Pharmaceutics, College of Pharmacy, The University of Texas at Austin.
    Brunaugh, Ashlee
    Division of Pharmaceutics, College of Pharmacy, The University of Texas at Austin.
    Ferrati, Siilvia
    Division of Pharmaceutics, College of Pharmacy, The University of Texas at Austin.
    Li, Song
    School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA.
    Montenegro-Nicolini, Miguel
    Department of Pharmaceutical Science and Technology, School of Chemical and Pharmaceutical Sciences, University of Chile.
    Mousavikhamene, Zeynab
    Chemical & Petroleum Engineering Department, Sharif University of Technology, Tehran.
    McConville, Jason Thomas
    College of Pharmacy, University of New Mexico, Albuquerque, NM.
    Prausnitz, Mark
    dSchool of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA.
    Smyth, Hugh David Charles
    Division of Pharmaceutics, College of Pharmacy, The University of Texas at Austin.
    Challenges and Future Prospects for the Delivery of Biologics: Oral Mucosal, Pulmonary, and Transdermal Routes2017In: AAPS Journal, E-ISSN 1550-7416, Vol. 19, no 3, p. 652-668Article in journal (Refereed)
    Abstract [en]

    Biologic products are large molecules such as proteins, peptides, nucleic acids, etc., which have already produced many new drugs for clinical use in the last decades. Due to the inherent challenges faced by biologics after oral administration (e.g., acidic stomach pH, digestive enzymes, and limited permeation through the gastrointestinal tract), several alternative routes of administration have been investigated to enable sufficient drug absorption into systemic circulation. This review describes the buccal, sublingual, pulmonary, and transdermal routes of administration for biologics with relevant details of the respective barriers. While all these routes avoid transit through the gastrointestinal tract, each has its own strengths and weaknesses that may be optimal for specific classes of compounds. Buccal and sublingual delivery enable rapid drug uptake through a relatively permeable barrier but are limited by small epithelial surface area, stratified epithelia, and the practical complexities of maintaining a drug delivery system in the mouth. Pulmonary delivery accesses the highly permeable and large surface area of the alveolar epithelium but must overcome the complexities of safe and effective delivery to the alveoli deep in the lung. Transdermal delivery offers convenient access to the body for extended-release delivery via the skin surface but requires the use of novel devices and formulations to overcome the skin’s formidable stratum corneum barrier. New technologies and strategies advanced to overcome these challenges are reviewed, and critical views in future developments of each route are given.

  • 15.
    Morales, Javier O.
    et al.
    University of Texas at Austin, College of Pharmacy, 1 University Station .
    Horng, Michelle
    University of Texas at Austin, College of Pharmacy, 1 University Station .
    Gregg, Aubrey M.
    University of Texas at Austin, College of Pharmacy, 1 University Station .
    McConville, Jason T
    University of Texas at Austin, College of Pharmacy, 1 University Station .
    Orally disintegrating tablets using starch and fructose2010In: Pharmaceutical Technology, ISSN 1543-2521, Vol. 34, no 11, p. 92-99Article in journal (Refereed)
  • 16.
    Morales, Javier O.
    et al.
    Department of Pharmaceutical Science and Technology, School of Chemical and Pharmaceutical Sciences, University of Chile, Santiago .
    Huang, Siyuan
    College of Pharmacy, The University of Texas at Austin, Austin, TX .
    Williams, Robert O
    College of Pharmacy, The University of Texas at Austin, Austin, TX.
    McConville, Jason T
    cCollege of Pharmacy, University of New Mexico, Albuquerque, NM .
    Films loaded with insulin-coated nanoparticles (ICNP) as potential platforms for peptide buccal delivery2014In: Colloids and Surfaces B: Biointerfaces, ISSN 0927-7765, E-ISSN 1873-4367, Vol. 122, p. 38-45Article in journal (Refereed)
    Abstract [en]

    The goal of this investigation was to develop films containing insulin-coated nanoparticles and evaluate their performance in vitro as potential peptide delivery systems. To incorporate insulin into the films, a new antisolvent co-precipitation fabrication process was adapted to obtain insulin-coated nanoparticles (ICNPs). The ICNPs were embedded in polymeric films containing a cationic polymethacrylate derivative (ERL) or a combination of ERL with hydroxypropyl methylcellulose (HPMC). ICNP-loaded films were characterized for morphology, mucoadhesion, and insulin release. Furthermore, in vitro insulin permeation was evaluated using a cultured tridimensional human buccal mucosa model. The antisolvent co-precipitation method was successfully adapted to obtain ICNPs with 40% (w/w) insulin load, achieving 323±8nm particles with a high zeta potential of 32.4±0.8mV, indicating good stability. High yields were obtained after manufacture and the insulin content did not decrease after one month storage. ICNP-embedded films using ERL as the polymer matrix presented excellent mucoadhesive and insulin release properties. A high permeation enhancement effect was observed for ICNP-loaded ERL films in comparison with ICNP-loaded ERL-HPMC films and a control insulin solution. ICNP-loaded ERL formulations were found to be more effective in terms of film performance and insulin permeation through the human buccal mucosa model, and thus are a promising delivery system for buccal administration of a peptide such as insulin.

  • 17.
    Morales, Javier O.
    et al.
    College of Pharmacy, University of Texas at Austin .
    Joks, Gero M
    bPharmazeutischeTechnologie, Pharmazeutisches Institut der Universität Bonn.
    Lamprecht, Alf
    bPharmazeutischeTechnologie, Pharmazeutisches Institut der Universität Bonn.
    Ross, Alistair C
    Controlled Therapeutics (Scotland) Ltd.
    McConville, Jason T
    College of Pharmacy, University of Texas at Austin.
    A design of experiments to optimize a new manufacturing process for high activity protein-containing submicron particles2013In: Drug Development and Industrial Pharmacy, ISSN 0363-9045, E-ISSN 1520-5762, Vol. 39, no 11, p. 1793-1801Article in journal (Refereed)
    Abstract [en]

    A novel method for the manufacture of protein/peptide-containing submicron particles was developed in an attempt to provide particles with increased activity while using high energy input technologies. The method consists of antisolvent co-precipitation from an aqueous solution containing both an amino acid core material (e.g. D,L-valine), and either bovine serum albumin (BSA) or lysozyme (Lys) as model proteins. The aqueous solution was added to the organic phase by means of a nebulizer to increase the total surface area of interaction for the precipitation process. Sonication proved to be an effective method to produce small particle sizes while maintaining high activity of Lys. The use of a polysorbate or sorbitan ester derivatives as stabilizers proved to be necessary to yield submicron particles. Particles with very high yields (approximately 100%) and very high activity after manufacture (approximately 100%) could be obtained. A particle size of 439.0 nm, with a yield of 48.8% and with final remaining activity of 98.7% was obtained. By studying various factors using a design of experiments strategy (DoE) we were able to establish the critical controlling factors for this new method of manufacture.

  • 18.
    Morales, Javier O.
    et al.
    College of Pharmacy, University of Texas at Austin.
    McConville, Jason T
    College of Pharmacy, University of Texas at Austin.
    Manufacture and characterization of mucoadhesive buccal films2011In: European journal of pharmaceutics and biopharmaceutics, ISSN 0939-6411, E-ISSN 1873-3441, Vol. 77, no 2, p. 187-199Article in journal (Refereed)
    Abstract [en]

    The buccal route of administration has a number of advantages including bypassing the gastrointestinal tract and the hepatic first pass effect. Mucoadhesive films are retentive dosage forms and release drug directly into a biological substrate. Furthermore, films have improved patient compliance due to their small size and reduced thickness, compared for example to lozenges and tablets. The development of mucoadhesive buccal films has increased dramatically over the past decade because it is a promising delivery alternative to various therapeutic classes including peptides, vaccines, and nanoparticles. The "film casting process" involves casting of aqueous solutions and/or organic solvents to yield films suitable for this administration route. Over the last decade, hot-melt extrusion has been explored as an alternative manufacturing process and has yielded promising results. Characterization of critical properties such as the mucoadhesive strength, drug content uniformity, and permeation rate represent the major research areas in the design of buccal films. This review will consider the literature that describes the manufacture and characterization of mucoadhesive buccal films.

  • 19.
    Morales, Javier O.
    et al.
    Department of Pharmaceutical Science and Technology, School of Chemical and Pharmaceutical Sciences, University of Chile.
    McConville, Jason T
    College of Pharmacy, University of New Mexico, Albuquerque, NM.
    Novel strategies for the buccal delivery of macromolecules2014In: Drug Development and Industrial Pharmacy, ISSN 0363-9045, E-ISSN 1520-5762, Vol. 40, no 5, p. 579-590Article in journal (Refereed)
    Abstract [en]

    For years now, the delivery of small molecules through the buccal mucosal route has been described in the literature, but it has only been over the past decade that investigations into macromolecule delivery via the buccal route have sharply increased. The administration of macromolecules such as proteins and peptides, antibodies, or nucleic acids by buccal administration would be greatly enhanced due to the avoidance of the gastrointestinal conditions, rapid uptake into systemic circulation, as well as the potential for controlled drug delivery. Since macromolecules are faced with a number of specific challenges related to permeation through the epithelium, several strategies have been employed historically to improve their buccal absorption and subsequent bioavailability. Several conventional strategies to improve macromolecule penetration include the use of chemical permeation enhancers, enzyme inhibitors and the use of mucoadhesive materials acting as carriers. More recent approaches include the incorporation of the macromolecule as part of nanostructured delivery systems to further enhance targeting and delivery. This review focuses on the different permeation enhancing strategies as well as formulation design that are tailored to meet the challenges of active macromolecule delivery using the buccal mucosal route of administration.

  • 20.
    Morales, Javier O.
    et al.
    Department of Pharmaceutical Sciences and Technology, University of Chile.
    McConville, Jason T
    College of Pharmacy, University of New Mexico, Albuquerque, NM.
    Preface for buccal drug delivery theme issue2014In: Drug Development and Industrial Pharmacy, ISSN 0363-9045, E-ISSN 1520-5762, Vol. 40, no 5, p. 577-578Article in journal (Other academic)
    Abstract [en]

    During the past years, buccal drug delivery has attracted the attention of researchers looking for alternative delivery routes of administration. As an alternative to oral drug delivery, the buccal mucosal route avoids the passage through the acidic gastric environment, intestinal and bacterial enzymatic activity, absorption issues associated with the intestinal epithelium (e.g. P-glycoprotein efflux), and the first pass metabolism of the liver. Therefore, the buccal route could be a good delivery route for macromolecules and other drugs not compatible with the gastrointestinal tract environment. This "Buccal Drug Delivery" special edition of Drug Development and Industrial Pharmacy aims to bring together a range of different aspects relevant to the growing field of buccal drug delivery. The special edition includes thorough reviews of the literature, as well as original research articles touching on most prominent features related to buccal drug delivery systems, such as the move toward the use of nanotechnology in different ways to facilitate buccal drug delivery with the potential to prompt future product developments.

  • 21.
    Morales, Javier O.
    et al.
    Advanced Internal Medicine Group, New York, USA.
    Merker, Ludwig
    Diabetes und Nierenzentrum Dormagen, Dormagen, Germany.
    Minimizing Hypoglycemia and Weight Gain with Intensive Glucose Control: Potential Benefits of a New Combination Therapy (IDegLira)2015In: Advances in Therapy, ISSN 0741-238X, E-ISSN 1865-8652, Vol. 32, no 5, p. 391-403Article in journal (Refereed)
    Abstract [en]

    Due to the progressive nature of type 2 diabetes (T2D), the majority of patients require increasing levels of therapy to achieve and maintain good glycemic control. At present, once patients become uncontrolled on oral antidiabetic therapies, the two primary treatment options are glucagon-like peptide-1 receptor agonists (GLP-1RAs) or basal insulin, although earlier use of GLP-1RAs has also been advocated. While both of these drug classes have proven efficacy in treating T2D, there can be limitations to their use in some patients, and resistance to further treatment intensification among both patients and physicians. More recently, treatment incorporating both a GLP-1RA and a basal insulin has been used successfully in the clinic and the first such combination product, IDegLira (insulin degludec + liraglutide), has recently been approved for use in Europe. IDegLira combines insulin degludec and the GLP-1RA liraglutide in a single injection. In both insulin-naïve and basal insulin-treated individuals with T2D, IDegLira has demonstrated greater reductions in glycated hemoglobin (HbA1c) than either of the individual components, with a low rate of hypoglycemia and weight loss. IDegLira may provide a new option for patients requiring treatment intensification but for whom increased weight or a higher risk of hypoglycemia are barriers. This article discusses the rationale behind combining these two drug classes and reviews the available clinical evidence for the efficacy and safety of IDegLira

  • 22.
    Morales, Javier O.
    et al.
    Department of Pharmaceutical Sciences and Technology, University of Chile.
    Montenegro-Nicolini, Miguel
    Department of Pharmaceutical Sciences and Technology, University of Chile.
    Campano-Hantscheruk, F.
    Department of Pharmaceutical Science and Technology, School of Chemical and Pharmaceutical Sciences, University of Chile, Santiago.
    Miranda, Victor
    Department of Pharmaceutical Science and Technology, School of Chemical and Pharmaceutical Sciences, University of Chile, Santiago.
    Inkjet Printing of Biologics Inks and Biologics-Loaded Nanodispersionson Polymeric Films as Potential Buccal Drug Delivery Systems2016Conference paper (Refereed)
  • 23.
    Morales, Javier O.
    et al.
    Division of Pharmaceutics, College of Pharmacy, University of Texas at Austin.
    Peters, Jay I.
    Department of Pulmonary Care, College of Medicine, University of Texas Health Science Center at San Antonio.
    Williams, Robert O
    Division of Pharmaceutics, College of Pharmacy, University of Texas at Austin.
    Surfactants: their critical role in enhancing drug delivery to the lungs2011In: Therapeutic delivery, ISSN 2041-5990, E-ISSN 2041-6008, Vol. 2, no 5, p. 623-641Article in journal (Refereed)
    Abstract [en]

    For local lung conditions and diseases, pulmonary drug delivery has been widely used for more than 50 years now. A more recent trend involves the pulmonary route as a systemic drug-delivery target. Advantages such as avoidance of the gastrointestinal environment, different enzyme content compared with the intestine, and avoidance of first-pass metabolism make the lung an alternative route for the systemic delivery of actives. However, the lung offers barriers to absorption such as a surfactant layer, epithelial surface lining fluid, epithelial monolayer, interstitium and basement membrane, and capillary endothelium. Many delivery strategies have been developed in order to overcome these limitations. The use of surfactants is one of these approaches and their role in enhancing pulmonary drug delivery is reviewed in this article. A systematic review of the literature relating to the effect of surfactants on formulations for pulmonary delivery was conducted. Specifically, research reporting enhancement of in vivo performance was focused on. The effect of the addition of surfactants such as phospholipids, bile salts, non-ionic, fatty acids, and liposomes as phospholipid-containing carriers on the enhancement of therapeutic outcomes of drugs for pulmonary delivery was compiled. The main use attributed to surfactants in pulmonary drug delivery is as absorption enhancers by mechanisms of action not yet fully understood. Furthermore, surfactants have been used to improve the delivery of inhaled drugs in various additional strategies discussed herein.

  • 24.
    Morales, Javier O.
    et al.
    College of Pharmacy, The University of Texas at Austin, Austin, TX, USA;School of Chemical and Pharmaceutical Sciences, University of Chile, Santiago, Chile.
    Ross, Alistair C.
    Ferring Controlled Therapeutics Ltd, East Kilbride, Scotland, UK.
    McConville, Jason T.
    University of New Mexico, Albuquerque, NM, USA.
    Protein-coated nanoparticles embedded in films as delivery platforms2013In: Journal of Pharmacy and Pharmacology (JPP), ISSN 0022-3573, E-ISSN 2042-7158, Vol. 65, no 6, p. 827-838Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: This work aimed to evaluate the performance of nanoparticle-loaded films based on matrices of polymethacrylates and hydroxypropylmethylcellulose (HPMC) intended for delivery of macromolecules.

    METHODS: Lysozyme (Lys)-loaded nanoparticles were manufactured by antisolvent co-precipitation. After size, loading efficiency and stability characterization, the selected batch of particles was further formulated into films. Films were characterized for mechanical properties, mucoadhesion, Lys release and activity after manufacture.

    KEY FINDINGS: We found that protein-coated nanoparticles could be obtained in USP phosphate buffer pH 6.8. Particles obtained at pH 6.8 had a z-average of 347.2 nm, a zeta-potential of 21.9 mV and 99.2% remaining activity after manufacture. This formulation was further studied for its application in films for buccal delivery. Films loaded with nanoparticles that contained Eudragit RLPO (ERL) exhibited excellent mechanical and mucoadhesive properties. Due to its higher water-swelling and solubility compared with ERL, the use of HPMC allowed us to tailor the release of Lys from films. The formulation composed of equal amounts of ERL and HPMC revealed a sustained release over 4 h, with Lys remaining fully active at the end of the study.

    CONCLUSIONS: Mucoadhesive films containing protein-coated nanoparticles are promising carriers for the buccal delivery of proteins and peptides in a stable form.

  • 25.
    Morales, Javier O.
    et al.
    Department of Pharmaceutical Sciences and Technology, University of Chile.
    Sepulveda-Rivas, Sabrina
    Department of Pharmaceutical Sciences and Technology, University of Chile.
    Oyarzun-Ampuero, Felipe
    Department of Pharmaceutical Sciences and Technology, University of Chile.
    Lavandero, Sergio
    Department of Biochemistry & Molecular Biology, University of Chile.
    Kogan, Marcelo J
    Department of Pharmacological and Toxicological Chemistry, University of Chile.
    Novel Nanostructured Polymeric Carriers to Enable Drug Delivery for Cardiovascular Diseases2015In: Current pharmaceutical design, ISSN 1381-6128, E-ISSN 1873-4286, Vol. 21, no 29, p. 4276-4284Article in journal (Refereed)
    Abstract [en]

    Applications of polymeric nanotechnologies for enabling therapies for cardiovascular diseases have shown recent success. Both intravenous and oral administration have been investigated and achieved different degrees of development. While circulating polymeric nanostructured carriers are subjected to a number of interactions, smart nanoparticle design has enabled the formulation of active molecules to be delivered to specific targets for cardiovascular effects. This review aims at outlining the multiple factors that can affect the fate of polymeric nanostructured carriers in systemic circulation. With an understanding of these factors, the literature on the various polymeric nanostructured carriers is reviewed. Finally, the emerging uses of nanotechnology to formulate orally administered drugs for cardiovascular diseases are depicted.

  • 26.
    Morales, Javier O.
    et al.
    College of Pharmacy, University of Texas at Austin.
    Su, Rong
    Department of Pharmacy and Pharmacology, University of Bath.
    McConville, Jason T
    College of Pharmacy, University of Texas at Austin.
    The influence of recrystallized caffeine on water-swellable polymethacrylate mucoadhesive buccal films2013In: AAPS PharmSciTech, E-ISSN 1530-9932, Vol. 14, no 2, p. 475-484Article in journal (Refereed)
    Abstract [en]

    The aim of this work was to investigate the influence of particles on the properties of polymethacrylate films intended for buccal delivery. A solvent casting method was used with Eudragit RS and RL (ERS and ERL, respectively) as film-forming rate-controlling polymers, with caffeine as a water-soluble model drug. The physicochemical properties of the model films for a series of formulations with increasing concentrations of caffeine were determined in terms of morphology, mechanical and mucoadhesive properties, drug content uniformity, and drug release and associated kinetics. Typically regarded as non-mucoadhesive polymers, ERS and mainly ERL, were found to be good mucoadhesives, with ERL01 exhibiting a work of mucoadhesion (WoA) of 118.9 μJ, which was about five to six times higher than that observed for commonly used mucoadhesives such as Carbopol(®) 974P (C974P, 23.9 μJ) and polycarbophil (PCP, 17.4 μJ). The mucoadhesive force for ERL01 was found to be significantly lower yet comparable to C974P and PCP films (211.1 vs. 329.7 and 301.1 mN, respectively). Inspection of cross-sections of the films indicated that increasing the concentration of caffeine was correlated with the appearance of recrystallized agglomerates. In conclusion, caffeine agglomerates had detrimental effects in terms of mucoadhesion, mechanical properties, uniformity, and drug release at large particle sizes. ERL series of films exhibited very rapid release of caffeine while ERS series showed controlled release. Analysis of release profiles revealed that kinetics changed from a diffusion controlled to a first-order release mechanism.

  • 27.
    Morales, Javier O.
    et al.
    Department of Sciences and Pharmaceutical Technologies, University of Chile, Santos-Dumont, Santiago.
    Valdés, Karina
    Department of Sciences and Pharmaceutical Technologies, University of Chile, Santos-Dumont, Santiago.
    Morales, Javier
    Department of Sciences and Pharmaceutical Technologies, University of Chile, Santos-Dumont, Santiago.
    Oyarzun-Ampuero, Felipe
    Department of Sciences and Pharmaceutical Technologies, University of Chile, Santos-Dumont, Santiago.
    Lipid nanoparticles for the topical delivery of retinoids and derivatives2015In: Nanomedicine, ISSN 1743-5889, E-ISSN 1748-6963, Vol. 10, no 2, p. 253-269Article in journal (Refereed)
    Abstract [en]

    Retinoids are lipophilic compounds that are highly used in cosmetics/therapeutics for skin disorders. Conventional formulations are limited by poor water solubility, high chemical/photochemical instability and the irritation of retinoids. Interestingly, lipid nanoparticles enable the administration of retinoids in aqueous media, providing drug stabilization and controlled release. Recently, it has been demonstrated that retinoids in solid lipid nanoparticles, nanostructured lipid carriers, nanoemulsions and nanocapsules can decrease degradation, improve targeting and enhance efficacy for the treatment of skin disorders. This article focuses on the formulation, fabrication, characterization and in vitro/in vivo evaluation of solid lipid nanoparticles, nanostructured lipid carriers, nanoemulsions and nanocapsules loaded with retinoids for skin administration. Furthermore, the incorporation of these lipid nanoparticles into secondary vehicles is discussed.

  • 28.
    Ortiz, Andrea C.
    et al.
    Department of Pharmaceutical Science and Technology, School of Chemical and Pharmaceutical Sciences, University of Chile, Santiago, Chile. Advanced Center for Chronic Diseases (ACCDiS), Santiago, Chile.
    Morales, Javier O.
    Luleå University of Technology, Department of Health Sciences, Medical Science. Department of Pharmaceutical Science and Technology, School of Chemical and Pharmaceutical Sciences, University of Chile, Santiago, Chile. Advanced Center for Chronic Diseases (ACCDiS), Santiago, Chile.
    Buccal Delivery of Nanoparticles2020In: Mucosal Delivery of Drugs and Biologics in Nanoparticles / [ed] Pavan Muttil, Nitesh K. Kunda, Springer, 2020, p. 107-124Chapter in book (Other academic)
    Abstract [en]

    The buccal route offers an alternative for drug administration due to its advantages, including the avoidance of the gastrointestinal tract, the hepatic first-pass, enzymatic degradation and chemical instability of certain molecules that would pose a challenge to formulate orally. Moreover, the oral cavity has a lower enzyme content than the rest of the gastrointestinal tract, predictable transit times, easy administration, and provides the opportunity to readily halt drug administration. Additionally, the oral cavity is an organized system with stratified epithelium that allows manufacturing of pharmaceutical forms for drug delivery.

    Due to the possibilities offered by this route, recent research efforts have been conducted towards the use of nanotechnology to enable buccal drug delivery. In this chapter, we discuss the anatomy of the oral cavity, relevant characteristics of the epithelium to drug delivery and delivery system permeation, types of nanocarriers that have been reported to-date and toxicity studies addressing nanotechnology.

  • 29.
    Oyarzun-Ampuero, Felipe
    et al.
    Departamento de Ciencias y Tecnología Farmacéuticas, Universidad de Chile, Santiago, Chile.
    Guerrero, Ariel
    Advancer Center for Chronic Diseases (ACCDiS), Santiago.
    Hassan-Lopez, Natalia
    Advancer Center for Chronic Diseases (ACCDiS), Santiago.
    Morales, Javier O.
    Luleå University of Technology, Department of Health Sciences, Medical Science. Departamento de Ciencias y Tecnología Farmacéuticas, Universidad de Chile, Santiago.
    Bollo, Soledad
    Advancer Center for Chronic Diseases (ACCDiS), Santiago.
    Corvalan, Alejandro
    Advancer Center for Chronic Diseases (ACCDiS), Santiago.
    Quest, Andrew F G
    Advancer Center for Chronic Diseases (ACCDiS), Santiago.
    Kogan, Marcelo J
    Departamento de Ciencias y Tecnología Farmacéuticas, Universidad de Chile, Santiago.
    Organic and Inorganic Nanoparticles for Prevention and Diagnosis of Gastric Cancer2015In: Current pharmaceutical design, ISSN 1381-6128, E-ISSN 1873-4286, Vol. 21, no 29, p. 4145-4154Article in journal (Refereed)
    Abstract [en]

    Organic and inorganic nanoparticles show great potential for cancer diagnosis and treatment. Because gastric cancer (GC) represents the second most deadly type of neoplasia worldwide, continued research efforts by scientists and clinicians are essential to improve diagnosis and treatment. This paper reviews significant findings in the area of nanoparticles (organic and inorganic origin) that may aid in prevention and diagnosis of GC. This review focuses in the first section on H. pylori and the connection to GC, highlighting nanoformulations designed to control bacterial growth. The second section evaluates the potential of different imaging techniques (especially using inorganic nanoparticles) in the detection of GC, and the third section summarizes how nanotechnology may be employed in the analytical detection of GC biomarkers (metallic plasmons, electrochemical biosensors and colorimetric sensors). We foresee that the prevention and diagnosis of GC will require the development of complex collaborative studies. Additionally, scientists also need to be tightly connected to industry in order to facilitate upscaling and rapid transfer of promising products to the clinic.

  • 30.
    Oyarzun-Ampuero, Felipe
    et al.
    Departamento de Ciencias y Tecnología Farmacéuticas, Universidad de Chile, Santiago.
    Vidal, Alejandra
    Instituto de Anatomía Histología y Patología, Universidad Austral de Chile, Valdivia.
    Concha, Miguel
    Instituto de Anatomía Histología y Patología, Universidad Austral de Chile, Valdivia.
    Morales, Javier O.
    Luleå University of Technology, Department of Health Sciences, Health and Rehabilitation. Departamento de Ciencias y Tecnología Farmacéuticas, Universidad de Chile, Santiago, Chile.
    Orellana, Sandra
    Instituto de Ciencias Químicas, Universidad Austral de Chile, Isla Teja, Casilla,Valdivia.
    Moreno-Villoslada, Ignacio
    Instituto de Ciencias Químicas, Universidad Austral de Chile, Isla Teja, Casilla,Valdivia.
    Nanoparticles for the Treatment of Wounds2015In: Current pharmaceutical design, ISSN 1381-6128, E-ISSN 1873-4286, Vol. 21, no 29, p. 4329-4341Article in journal (Refereed)
    Abstract [en]

    The treatment of skin wounds represents an important research area due to the important physiological and aesthetic role of this tissue. During the last years, nanoparticles have emerged as important platforms to treat skin wounds. Silver, gold, and copper nanoparticles, as well as titanium and zinc oxide nanoparticles, have shown potential therapeutic effects on wound healing. Due to their specific characteristics, nanoparticles such as nanocapsules, polymersomes, solid lipid nanoparticles, and polymeric nanocomplexes are ideal vehicles to improve the effect of drugs (antibiotics, growth factors, etc.) aimed at wound healing. On the other hand, if active excipients are added during the formulation, such as hyaluronate or chitosan, the nanomedicine could significantly improve its potential. In addition, the inclusion of nanoparticles in different pharmaceutical materials may enhance the beneficial effects of the formulations, and allow achieving a better dose control. This paper aims at reviewing significant findings in the area of nanoparticles and wound treatment. Among the reviewed topics, we underline formulations comprising inorganic, polymeric, surfactant self-assembled, and lipid nanosystems. Among the drugs included in the nanoformulations, the paper refers to antibiotics, natural extracts, proteins, and growth factors, among others. Finally, the paper also addresses nanoparticles embedded in secondary vehicles (fibers, dressings, hydrogels, etc.) that could improve their application and/or upgrade the release profile of the active.

  • 31.
    Rao Vuddanda, Parameswara
    et al.
    Luleå University of Technology, Department of Health Sciences, Medical Science.
    Montenegro-Nicolini, Miguel
    Department of Pharmaceutical Sciences and Technology, University of Chile, Santiago.
    Morales, Javier O.
    Department of Pharmaceutical Sciences and Technology, University of Chile, Santiago.
    Velaga, Sitaram
    Luleå University of Technology, Department of Health Sciences, Medical Science.
    Effect of plasticizers on the physico-mechanical properties of pullulan based pharmaceutical oral films2017In: European Journal of Pharmaceutical Sciences, ISSN 0928-0987, E-ISSN 1879-0720, Vol. 96, p. 290-298Article in journal (Refereed)
    Abstract [en]

    The effect of different plasticizers (glycerol, vitamin E TPGS and triacetin) and their concentrations on the physico-mechanical properties of pullulan based oral films was studied. A full factorial (32) design of experiments was used. Elastic modulus, tensile strength, elongation at break and disintegration time were selected as response variables. Modulated differential scanning calorimeter (MDSC) was used for determining glass transition temperature (Tg) of pullulan films. The surface morphology of films was evaluated by SEM, while ATR-FTIR was used to obtain a molecular level understanding of polymer-plasticizer interactions. The DoE analysis allowed for the modelling of tensile strength and elongation at break. The highest elongations were observed in glycerol at 20% w/w. Majority of the films disintegrated within one minute without significant differences. ATR-FTIR spectra of pullulan alone and different plasticizer blend films show characteristic molecular interactions. The present study concluded that glycerol is suitable plasticizer compared to others for manufacturing pullulan based oral films.

  • 32.
    Rao Vuddanda, Parameswara
    et al.
    Luleå University of Technology, Department of Health Sciences, Medical Science.
    Montenegro-Nicolini, Miguel
    Department of Pharmaceutical Sciences and Technology, University of Chile.
    Morales, Javier O.
    Luleå University of Technology, Department of Health Sciences, Medical Science.
    Velaga, Sitaram
    Luleå University of Technology, Department of Health Sciences, Medical Science.
    Effect of surfactants and drug load on physico-mechanical and dissolution properties of nanocrystalline tadalafil-loaded oral films2017In: European Journal of Pharmaceutical Sciences, ISSN 0928-0987, E-ISSN 1879-0720, Vol. 109, p. 372-380Article in journal (Refereed)
    Abstract [en]

    The aim of the present work was to prepare tadalafil (TDF) nanocrystals-loaded oral polymeric films (OFs) and investigate the effect of hydrophilic surfactants and drug loads on the physico-mechanical and dissolution properties. The nanosuspensions of TDF were prepared by high shear homogenization. HPMC based placebo casting film gel was prepared and mixed with TDF nanosuspensions. Films were casted using an automated film applicator and dried at 60 °C for 45 min. Particle size (PS), polydispersity index (PDI), and zeta potential (ZP) of TDF nanosuspensions were measured in a Zetasizer. The films were characterized using SEM, AFM, DSC, TGA and PXRD. The mechanical properties and in vitro drug release were determined using standard methods. TDF existed in crystalline form and the particles remained in the nano-range in redispersed films. TDF nanocrystals were embedded in the polymeric matrix and the drug loaded films were rough on the surface. Mechanical properties of the films varied with changes in drug load and surfactant. Significant changes in the disintegration times were noticed in films containing surfactants compared to surfactant-free films. About 80% of the drug release was observed between 3 and 30 min. TPGS showed better TDF release from the films at different drug loads

  • 33.
    Valdés, Karina
    et al.
    Departamento de Ciencias y Tecnología Farmacéutica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago, Chile.
    Morales, Javier
    Departamento de Ciencias y Tecnología Farmacéutica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago, Chile.
    Rodríguez, Lennin
    Facultad de Farmacia y Bioquímica, Universidad Nacional de Trujillo, Trujillo, Perú.
    Günther, German
    Departamento de Química Orgánica y Fisicoquímica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago, Chile.
    Potential use of nanocarriers with pentacyclic triterpenes in cancer treatments2016In: Nanomedicine, ISSN 1743-5889, E-ISSN 1748-6963, Vol. 12, no 23, p. 3139-3156Article in journal (Refereed)
    Abstract [en]

    Ursolic, oleanolic and betulinic acids are representative pentacyclic triterpenoids found in various plants and fruits. Despite having marked antitumor potentials, the very poor water solubility of these triterpenes hinders treatment development. Nanotechnology can enhance solubility, stability, bioavailability and phytochemical delivery, improving the therapeutic efficiency of triterpenes. This review focuses on the formulation, characterization and in vitro/in vivo evaluation of several delivery nanosystems used to enhance the physicochemical properties of ursolic, oleanolic and betulinic acids.

  • 34. Yazidi, A.K.
    et al.
    Morales, Javier O.
    Marek, S.R.
    Thielmann, F.
    Burnett, D.
    Heng, J.
    McConville, Jason T
    College of Pharmacy, University of Texas at Austin.
    Dissolution Rate Comparison of Micronized and Spray-Dried Budesonide2012In: RDD 2012 Arizona, Respiratory Drug Delivery (RDD) , 2012, p. 855-858Conference paper (Refereed)
1 - 34 of 34
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