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Intranasal delivery of asenapine loaded nanostructured lipid carriers: formulation, characterization, pharmacokinetic and behavioural assessment
Department of Pharmaceutics, Indian Institute of Technology, Banaras Hindu University, Varanas.
Pharma Research, Lupin Limited (Research Park), Pune.
Luleå tekniska universitet, Institutionen för hälsovetenskap, Medicinsk vetenskap.ORCID-id: 0000-0003-2645-5719
Department of Pharmaceutics, Indian Institute of Technology, Banaras Hindu University, Varanas.
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2016 (Engelska)Ingår i: RSC Advances, ISSN 2046-2069, E-ISSN 2046-2069, Vol. 6, nr 3, s. 2032-2045Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

The aim of the present research work was to develop asenapine (ASM) loaded nanostructured lipid carriers (ANLC) for the delivery of drugs in the brain by an intranasal route to enhance therapeutic efficacy. A quality by design approach was used for development and optimization of ANLC. A total of five independent variables were selected, in which three were compositions and two were process variables, while particle size and entrapment efficiency were selected as response variables. The final optimized batch was evaluated by various in vitro characterizations as well as in vivo brain and plasma pharmacokinetic studies. Finally, the ANLC was assessed for efficacy and safety profiling for upto three weeks by a behavior model viz. catalepsy, induced locomotor and paw test in Charles Foster rats. The observed particle size, entrapment efficiency and zeta potential of ANLC was found to be 167.30 +/- 7.52 nm, 83.50 +/- 2.48% and -4.33 +/- 1.27 mV, respectively. Surface characterization studies demonstrated a spherical shape with a smooth surface of ANLC which follows the Korsmeyer-Peppas in vitro release kinetic model (r(2) = 0.9911, n = 0.53). A brain pharmacokinetic study indicated a significantly higher (p < 0.05) peak drug concentration (C-max: 74.13 +/- 6.73 ng mL(-1)), area under the drug concentration-time curve (AUC(0-24) (h): 560.93 +/- 27.85 h ng mL(-1)) and mean residence time (MRT: 7.1 +/- 0.13 h) of ANLC compared to ASM in the brain via an intranasal route. The results of behaviour studies of ANLC showed a significant decrease in extra-pyramidal side effects with increasing antipsychotic effect after 1-2 week(s) of treatment. These findings demonstrate that nanostructured lipid carriers could be a new promising drug delivery system for intranasal delivery of asenapine in the treatment of schizophrenia

Ort, förlag, år, upplaga, sidor
2016. Vol. 6, nr 3, s. 2032-2045
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Hälsovetenskap
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URN: urn:nbn:se:ltu:diva-12569DOI: 10.1039/c5ra19793gISI: 000368191100043Scopus ID: 2-s2.0-84954116864Lokalt ID: bbb87ad8-420c-47b4-83b9-e2aa02bed3ccOAI: oai:DiVA.org:ltu-12569DiVA, id: diva2:985520
Anmärkning
Validerad; 2016; Nivå 2; 20160205 (andbra)Tillgänglig från: 2016-09-29 Skapad: 2016-09-29 Senast uppdaterad: 2018-07-10Bibliografiskt granskad

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Vuddanda, Parameswara RaoVelaga, SitaramSingh, Sanjay

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