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Ortiz, A. C. & Morales, J. O. (2020). Buccal Delivery of Nanoparticles. In: Pavan Muttil, Nitesh K. Kunda (Ed.), Mucosal Delivery of Drugs and Biologics in Nanoparticles: (pp. 107-124). Springer
Open this publication in new window or tab >>Buccal Delivery of Nanoparticles
2020 (English)In: 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.

Place, publisher, year, edition, pages
Springer, 2020
Series
AAPS Advances in the Pharmaceutical Sciences Series, ISSN 2210-7371, E-ISSN 2210-738X ; 41
Keywords
Buccal absorption, Nanocarriers, Nanoparticle safey, Ex vivo permeation, Mucoadhesion, Buccal drug delivery
National Category
Other Health Sciences
Research subject
Health Science
Identifiers
urn:nbn:se:ltu:diva-80719 (URN)10.1007/978-3-030-35910-2_5 (DOI)2-s2.0-85090055148 (Scopus ID)
Note

ISBN för värdpublikation: 978-3-030-35909-6, 978-3-030-35910-2

Available from: 2020-09-07 Created: 2020-09-07 Last updated: 2020-09-07Bibliographically approved
Catalan-Figueroa, J., Boisset, C. B., Jara, M. O., Flores, M. E., Moreno-Villoslada, I., Fiedler, J. L. & Morales, J. O. (2018). A mechanistic approach for the optimization of loperamide loaded nanocarriers characterization: Diafiltration and mathematical modeling advantages. European Journal of Pharmaceutical Sciences, 125, 215-222
Open this publication in new window or tab >>A mechanistic approach for the optimization of loperamide loaded nanocarriers characterization: Diafiltration and mathematical modeling advantages
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2018 (English)In: European Journal of Pharmaceutical Sciences, ISSN 0928-0987, E-ISSN 1879-0720, Vol. 125, p. 215-222Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Elsevier, 2018
National Category
Other Health Sciences
Research subject
Health Science
Identifiers
urn:nbn:se:ltu:diva-71218 (URN)10.1016/j.ejps.2018.10.002 (DOI)000448169800022 ()30312746 (PubMedID)2-s2.0-85054709610 (Scopus ID)
Note

Validerad;2018;Nivå 2;2018-10-16 (johcin) 

Available from: 2018-10-16 Created: 2018-10-16 Last updated: 2019-03-27Bibliographically approved
Jara, M. O., Catalan-Figueroa, J., Landin, M. & Morales, J. O. (2018). Finding key nanoprecipitation variables for achieving uniform polymeric nanoparticles using neurofuzzy logic technology. Drug Delivery and Translational Research, 8(6), 1797-1806
Open this publication in new window or tab >>Finding key nanoprecipitation variables for achieving uniform polymeric nanoparticles using neurofuzzy logic technology
2018 (English)In: Drug Delivery and Translational Research, ISSN 2190-393X, E-ISSN 2190-3948 , Vol. 8, no 6, p. 1797-1806Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Springer, 2018
Keywords
Nanoprecipitation, Artificial neural networks, Polymeric nanoparticles, Nanoparticle production, Mixing time, Homogeneous nanoparticles
National Category
Other Health Sciences
Research subject
Health Science
Identifiers
urn:nbn:se:ltu:diva-67212 (URN)10.1007/s13346-017-0446-8 (DOI)000449290900018 ()29288356 (PubMedID)2-s2.0-85054721730 (Scopus ID)
Note

Validerad;2018;Nivå 2;2018-11-29 (inah)

Available from: 2018-01-10 Created: 2018-01-10 Last updated: 2023-01-09Bibliographically approved
Bejarano, J., Navarro-Marquez, M., Morales-Zavala, F., Morales, J. O., Garcia-Carvajal, I., Araya-Fuentes, E., . . . Kogan, M. (2018). Nanoparticles for diagnosis and therapy of atherosclerosis and myocardial infarction: evolution toward prospective theranostic approaches. Theranostics, 8(17), 4710-4732
Open this publication in new window or tab >>Nanoparticles for diagnosis and therapy of atherosclerosis and myocardial infarction: evolution toward prospective theranostic approaches
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2018 (English)In: Theranostics, ISSN 1838-7640, E-ISSN 1838-7640, Vol. 8, no 17, p. 4710-4732Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Ivyspring International Publisher, 2018
Keywords
Nanoparticles, theranostics, atherosclerosis, myocardial infarction, cardiovascular diseases
National Category
Other Health Sciences
Research subject
Health Science
Identifiers
urn:nbn:se:ltu:diva-71027 (URN)10.7150/thno.26284 (DOI)000444107300011 ()30279733 (PubMedID)2-s2.0-85053130172 (Scopus ID)
Note

Validerad;2018;Nivå 2;2018-09-28 (svasva)

Available from: 2018-09-28 Created: 2018-09-28 Last updated: 2023-05-06Bibliographically approved
Fritz, H. F., Ortiz, A. C., Velaga, S. & Morales, J. O. (2018). Preparation of a novel lipid-core micelle using a low-energy emulsification method. Drug Delivery and Translational Research, 8(6), 1807-1814
Open this publication in new window or tab >>Preparation of a novel lipid-core micelle using a low-energy emulsification method
2018 (English)In: Drug Delivery and Translational Research, ISSN 2190-393X, E-ISSN 2190-3948 , Vol. 8, no 6, p. 1807-1814Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Springer, 2018
Keywords
Lipid-core micelles, Low-energy method, Poorly water soluble drugs, Hot-melt emulsification, Nanocarriers
National Category
Other Health Sciences
Research subject
Health Science
Identifiers
urn:nbn:se:ltu:diva-68401 (URN)10.1007/s13346-018-0521-9 (DOI)000449290900019 ()29663150 (PubMedID)2-s2.0-85056114607 (Scopus ID)
Note

Validerad;2018;Nivå 2;2018-11-29 (inah)

Available from: 2018-04-18 Created: 2018-04-18 Last updated: 2023-01-09Bibliographically approved
Montenegro-Nicolin, M., Reyes, P. E., Jara, M. O., Vuddanda, P. R., Neira-Carrillo, A., Butto, N., . . . Morales, J. O. (2018). The Effect of Inkjet Printing over Polymeric Films as Potential Buccal Biologics Delivery Systems. AAPS PharmSciTech, 19(8), 3376-3387
Open this publication in new window or tab >>The Effect of Inkjet Printing over Polymeric Films as Potential Buccal Biologics Delivery Systems
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2018 (English)In: AAPS PharmSciTech, E-ISSN 1530-9932, Vol. 19, no 8, p. 3376-3387Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Springer, 2018
National Category
Other Health Sciences
Research subject
Health Science
Identifiers
urn:nbn:se:ltu:diva-69877 (URN)10.1208/s12249-018-1105-1 (DOI)000452258500007 ()29934803 (PubMedID)2-s2.0-85048895366 (Scopus ID)
Note

Validerad;2018;Nivå 2;2018-12-05 (svasva)

Available from: 2018-06-26 Created: 2018-06-26 Last updated: 2023-01-26Bibliographically approved
Morales, J. O. & Brayden, D. J. (2017). Buccal delivery of small molecules and biologics: of mucoadhesive polymers, films, and nanoparticles. Current opinion in pharmacology (Print), 36, 22-28
Open this publication in new window or tab >>Buccal delivery of small molecules and biologics: of mucoadhesive polymers, films, and nanoparticles
2017 (English)In: Current opinion in pharmacology (Print), ISSN 1471-4892, E-ISSN 1471-4973, Vol. 36, p. 22-28Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Elsevier, 2017
National Category
Other Health Sciences
Research subject
Health Science
Identifiers
urn:nbn:se:ltu:diva-65107 (URN)10.1016/j.coph.2017.07.011 (DOI)000419665100006 ()28800417 (PubMedID)2-s2.0-85026830309 (Scopus ID)
Note

Validerad; 2017; Nivå 2; 2017-08-15 (andbra)

Available from: 2017-08-15 Created: 2017-08-15 Last updated: 2018-07-10Bibliographically approved
Montero-Padilla, S., Velaga, S. & Morales, J. O. (2017). Buccal Dosage Forms: general Considerations for Pediatric Patients (ed.). AAPS PharmSciTech, 18(2), 273-282
Open this publication in new window or tab >>Buccal Dosage Forms: general Considerations for Pediatric Patients
2017 (English)In: AAPS PharmSciTech, E-ISSN 1530-9932, Vol. 18, no 2, p. 273-282Article in journal (Refereed) Published
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. 

Place, publisher, year, edition, pages
Springer, 2017
National Category
Other Health Sciences
Research subject
Health Science
Identifiers
urn:nbn:se:ltu:diva-11269 (URN)10.1208/s12249-016-0567-2 (DOI)000396923200007 ()27301872 (PubMedID)2-s2.0-84974851810 (Scopus ID)a33184f4-38ce-482e-968d-1d8e6738d1e5 (Local ID)a33184f4-38ce-482e-968d-1d8e6738d1e5 (Archive number)a33184f4-38ce-482e-968d-1d8e6738d1e5 (OAI)
Note

Validerad; 2017; Nivå 2; 2017-01-31 (andbra)

Available from: 2016-09-29 Created: 2016-09-29 Last updated: 2023-01-26Bibliographically approved
Morales, J. O., Fathe, K. R., Brunaugh, A., Ferrati, S., Li, S., Montenegro-Nicolini, M., . . . Smyth, H. D. (2017). Challenges and Future Prospects for the Delivery of Biologics: Oral Mucosal, Pulmonary, and Transdermal Routes. AAPS Journal, 19(3), 652-668
Open this publication in new window or tab >>Challenges and Future Prospects for the Delivery of Biologics: Oral Mucosal, Pulmonary, and Transdermal Routes
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2017 (English)In: AAPS Journal, E-ISSN 1550-7416, Vol. 19, no 3, p. 652-668Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Springer, 2017
National Category
Other Health Sciences
Research subject
Health Science
Identifiers
urn:nbn:se:ltu:diva-64383 (URN)10.1208/s12248-017-0054-z (DOI)000400565300007 ()28194704 (PubMedID)2-s2.0-85012302294 (Scopus ID)
Available from: 2017-06-22 Created: 2017-06-22 Last updated: 2023-08-28Bibliographically approved
Rao Vuddanda, P., Montenegro-Nicolini, M., Morales, J. O. & Velaga, S. (2017). Effect of plasticizers on the physico-mechanical properties of pullulan based pharmaceutical oral films. European Journal of Pharmaceutical Sciences, 96, 290-298
Open this publication in new window or tab >>Effect of plasticizers on the physico-mechanical properties of pullulan based pharmaceutical oral films
2017 (English)In: European Journal of Pharmaceutical Sciences, ISSN 0928-0987, E-ISSN 1879-0720, Vol. 96, p. 290-298Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Elsevier, 2017
National Category
Other Health Sciences
Research subject
Health Science
Identifiers
urn:nbn:se:ltu:diva-59707 (URN)10.1016/j.ejps.2016.09.011 (DOI)000390698200032 ()27629498 (PubMedID)2-s2.0-84992456215 (Scopus ID)
Note

Validerad; 2016; Nivå 2; 2016-10-12 (andbra)

Available from: 2016-10-12 Created: 2016-10-12 Last updated: 2021-05-27Bibliographically approved
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ORCID iD: ORCID iD iconorcid.org/0000-0002-3190-2168

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