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Boosting the Brain Delivery of Atazanavir through Nanostructured Lipid Carrier-Based Approach for Mitigating NeuroAIDS

Atazanavir (ATZ) presents poor brain availability when administered orally, which poses a major hurdle in its use as an effective therapy for the management of NeuroAIDS. The utilization of nanostructured lipid carriers (NLCs) in conjunction with the premeditated use of excipients can be a potential...

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Autores principales: Khan, Saif Ahmad, Rehman, Saleha, Nabi, Bushra, Iqubal, Ashif, Nehal, Nida, Fahmy, Usama A., Kotta, Sabna, Baboota, Sanjula, Md, Shadab, Ali, Javed
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7694775/
https://www.ncbi.nlm.nih.gov/pubmed/33172119
http://dx.doi.org/10.3390/pharmaceutics12111059
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author Khan, Saif Ahmad
Rehman, Saleha
Nabi, Bushra
Iqubal, Ashif
Nehal, Nida
Fahmy, Usama A.
Kotta, Sabna
Baboota, Sanjula
Md, Shadab
Ali, Javed
author_facet Khan, Saif Ahmad
Rehman, Saleha
Nabi, Bushra
Iqubal, Ashif
Nehal, Nida
Fahmy, Usama A.
Kotta, Sabna
Baboota, Sanjula
Md, Shadab
Ali, Javed
author_sort Khan, Saif Ahmad
collection PubMed
description Atazanavir (ATZ) presents poor brain availability when administered orally, which poses a major hurdle in its use as an effective therapy for the management of NeuroAIDS. The utilization of nanostructured lipid carriers (NLCs) in conjunction with the premeditated use of excipients can be a potential approach for overcoming the limited ATZ brain delivery. Methods: ATZ-loaded NLC was formulated using the quality by design-enabled approach and further optimized by employing the Box–Behnken design. The optimized nanoformulation was then characterized for several in vitro and in vivo assessments. Results: The optimized NLC showed small particle size of 227.6 ± 5.4 nm, high entrapment efficiency (71.09% ± 5.84%) and high drug loading capacity (8.12% ± 2.7%). The release pattern was observed to be biphasic exhibiting fast release (60%) during the initial 2 h, then trailed by the sustained release. ATZ-NLC demonstrated a 2.36-fold increase in the cumulative drug permeated across the rat intestine as compared to suspension. Pharmacokinetic studies revealed 2.75-folds greater C(max) in the brain and 4-fold improvement in brain bioavailability signifying the superiority of NLC formulation over drug suspension. Conclusion: Thus, NLC could be a promising avenue for encapsulating hydrophobic drugs and delivering it to their target site. The results suggested that increase in bioavailability and brain-targeted delivery by NLC, in all plausibility, help in improving the therapeutic prospects of atazanavir.
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spelling pubmed-76947752020-11-28 Boosting the Brain Delivery of Atazanavir through Nanostructured Lipid Carrier-Based Approach for Mitigating NeuroAIDS Khan, Saif Ahmad Rehman, Saleha Nabi, Bushra Iqubal, Ashif Nehal, Nida Fahmy, Usama A. Kotta, Sabna Baboota, Sanjula Md, Shadab Ali, Javed Pharmaceutics Article Atazanavir (ATZ) presents poor brain availability when administered orally, which poses a major hurdle in its use as an effective therapy for the management of NeuroAIDS. The utilization of nanostructured lipid carriers (NLCs) in conjunction with the premeditated use of excipients can be a potential approach for overcoming the limited ATZ brain delivery. Methods: ATZ-loaded NLC was formulated using the quality by design-enabled approach and further optimized by employing the Box–Behnken design. The optimized nanoformulation was then characterized for several in vitro and in vivo assessments. Results: The optimized NLC showed small particle size of 227.6 ± 5.4 nm, high entrapment efficiency (71.09% ± 5.84%) and high drug loading capacity (8.12% ± 2.7%). The release pattern was observed to be biphasic exhibiting fast release (60%) during the initial 2 h, then trailed by the sustained release. ATZ-NLC demonstrated a 2.36-fold increase in the cumulative drug permeated across the rat intestine as compared to suspension. Pharmacokinetic studies revealed 2.75-folds greater C(max) in the brain and 4-fold improvement in brain bioavailability signifying the superiority of NLC formulation over drug suspension. Conclusion: Thus, NLC could be a promising avenue for encapsulating hydrophobic drugs and delivering it to their target site. The results suggested that increase in bioavailability and brain-targeted delivery by NLC, in all plausibility, help in improving the therapeutic prospects of atazanavir. MDPI 2020-11-06 /pmc/articles/PMC7694775/ /pubmed/33172119 http://dx.doi.org/10.3390/pharmaceutics12111059 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Khan, Saif Ahmad
Rehman, Saleha
Nabi, Bushra
Iqubal, Ashif
Nehal, Nida
Fahmy, Usama A.
Kotta, Sabna
Baboota, Sanjula
Md, Shadab
Ali, Javed
Boosting the Brain Delivery of Atazanavir through Nanostructured Lipid Carrier-Based Approach for Mitigating NeuroAIDS
title Boosting the Brain Delivery of Atazanavir through Nanostructured Lipid Carrier-Based Approach for Mitigating NeuroAIDS
title_full Boosting the Brain Delivery of Atazanavir through Nanostructured Lipid Carrier-Based Approach for Mitigating NeuroAIDS
title_fullStr Boosting the Brain Delivery of Atazanavir through Nanostructured Lipid Carrier-Based Approach for Mitigating NeuroAIDS
title_full_unstemmed Boosting the Brain Delivery of Atazanavir through Nanostructured Lipid Carrier-Based Approach for Mitigating NeuroAIDS
title_short Boosting the Brain Delivery of Atazanavir through Nanostructured Lipid Carrier-Based Approach for Mitigating NeuroAIDS
title_sort boosting the brain delivery of atazanavir through nanostructured lipid carrier-based approach for mitigating neuroaids
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7694775/
https://www.ncbi.nlm.nih.gov/pubmed/33172119
http://dx.doi.org/10.3390/pharmaceutics12111059
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