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Nanosized Cubosomal Thermogelling Dispersion Loaded with Saquinavir Mesylate to Improve Its Bioavailability: Preparation, Optimization, in vitro and in vivo Evaluation
BACKGROUND: Low bioavailability and poor permeability of the blood–brain barrier are problematic when delivering therapeutic agents and particularly anti–human immunodeficiency virus therapy to the central nervous system. The intranasal route offers an alternative for central nervous system delivery...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Dove
2020
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7371439/ https://www.ncbi.nlm.nih.gov/pubmed/32764940 http://dx.doi.org/10.2147/IJN.S261855 |
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author | Hosny, Khaled M |
author_facet | Hosny, Khaled M |
author_sort | Hosny, Khaled M |
collection | PubMed |
description | BACKGROUND: Low bioavailability and poor permeability of the blood–brain barrier are problematic when delivering therapeutic agents and particularly anti–human immunodeficiency virus therapy to the central nervous system. The intranasal route offers an alternative for central nervous system delivery. Cubosomes have been reported as helpful vehicles for intranasal delivery of therapeutics to enable brain targeting. OBJECTIVE: In this study, we aimed to develop the intranasal cubosomal thermogelling dispersion of saquinavir mesylate for central nervous system delivery. METHODS: The Box–Behnken design was applied to study the effect of monoolein, Poloxamer 407, and polyvinyl alcohol as independent factors and the particle size, entrapment efficiency, gelation temperature, and stability index as responses. The optimized cubosomes were evaluated using transmission electron microscopy, ex vivo permeation, and in vivo pharmacokinetics. RESULTS: The optimized formula consisting of monoolein (8.96%), Poloxamer 407 (17.45%), and polyvinyl alcohol (7.5%) was prepared and evaluated. Higher values for the steady-state flux, permeability coefficient, and enhancement factor were observed for the cubosomal thermogelling dispersion of saquinavir during ex vivo permeation in comparison with an aqueous suspension of saquinavir. From the pharmacokinetic profile, the relative bioavailability for the intranasal optimized formula was approximately 12-fold higher when compared with oral aqueous suspension and 2.5-fold greater when compared to the intranasal aqueous suspension of saquinavir. CONCLUSION: Overall, the saquinavir-loaded cubosomal thermogelling formulation is promising for central nervous system delivery by intranasal administration. |
format | Online Article Text |
id | pubmed-7371439 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Dove |
record_format | MEDLINE/PubMed |
spelling | pubmed-73714392020-08-05 Nanosized Cubosomal Thermogelling Dispersion Loaded with Saquinavir Mesylate to Improve Its Bioavailability: Preparation, Optimization, in vitro and in vivo Evaluation Hosny, Khaled M Int J Nanomedicine Original Research BACKGROUND: Low bioavailability and poor permeability of the blood–brain barrier are problematic when delivering therapeutic agents and particularly anti–human immunodeficiency virus therapy to the central nervous system. The intranasal route offers an alternative for central nervous system delivery. Cubosomes have been reported as helpful vehicles for intranasal delivery of therapeutics to enable brain targeting. OBJECTIVE: In this study, we aimed to develop the intranasal cubosomal thermogelling dispersion of saquinavir mesylate for central nervous system delivery. METHODS: The Box–Behnken design was applied to study the effect of monoolein, Poloxamer 407, and polyvinyl alcohol as independent factors and the particle size, entrapment efficiency, gelation temperature, and stability index as responses. The optimized cubosomes were evaluated using transmission electron microscopy, ex vivo permeation, and in vivo pharmacokinetics. RESULTS: The optimized formula consisting of monoolein (8.96%), Poloxamer 407 (17.45%), and polyvinyl alcohol (7.5%) was prepared and evaluated. Higher values for the steady-state flux, permeability coefficient, and enhancement factor were observed for the cubosomal thermogelling dispersion of saquinavir during ex vivo permeation in comparison with an aqueous suspension of saquinavir. From the pharmacokinetic profile, the relative bioavailability for the intranasal optimized formula was approximately 12-fold higher when compared with oral aqueous suspension and 2.5-fold greater when compared to the intranasal aqueous suspension of saquinavir. CONCLUSION: Overall, the saquinavir-loaded cubosomal thermogelling formulation is promising for central nervous system delivery by intranasal administration. Dove 2020-07-16 /pmc/articles/PMC7371439/ /pubmed/32764940 http://dx.doi.org/10.2147/IJN.S261855 Text en © 2020 Hosny. http://creativecommons.org/licenses/by-nc/3.0/ This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). |
spellingShingle | Original Research Hosny, Khaled M Nanosized Cubosomal Thermogelling Dispersion Loaded with Saquinavir Mesylate to Improve Its Bioavailability: Preparation, Optimization, in vitro and in vivo Evaluation |
title | Nanosized Cubosomal Thermogelling Dispersion Loaded with Saquinavir Mesylate to Improve Its Bioavailability: Preparation, Optimization, in vitro and in vivo Evaluation |
title_full | Nanosized Cubosomal Thermogelling Dispersion Loaded with Saquinavir Mesylate to Improve Its Bioavailability: Preparation, Optimization, in vitro and in vivo Evaluation |
title_fullStr | Nanosized Cubosomal Thermogelling Dispersion Loaded with Saquinavir Mesylate to Improve Its Bioavailability: Preparation, Optimization, in vitro and in vivo Evaluation |
title_full_unstemmed | Nanosized Cubosomal Thermogelling Dispersion Loaded with Saquinavir Mesylate to Improve Its Bioavailability: Preparation, Optimization, in vitro and in vivo Evaluation |
title_short | Nanosized Cubosomal Thermogelling Dispersion Loaded with Saquinavir Mesylate to Improve Its Bioavailability: Preparation, Optimization, in vitro and in vivo Evaluation |
title_sort | nanosized cubosomal thermogelling dispersion loaded with saquinavir mesylate to improve its bioavailability: preparation, optimization, in vitro and in vivo evaluation |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7371439/ https://www.ncbi.nlm.nih.gov/pubmed/32764940 http://dx.doi.org/10.2147/IJN.S261855 |
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