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

Saif Ahmad Khan,Usama A Fahmy,Javed Ali,Nida Nehal,Sabna Kotta,Ashif Iqubal,Sanjula Baboota,Shadab Md,Bushra Nabi,Saleha Rehman

doi:10.3390/pharmaceutics12111059

Saif Ahmad Khan, Usama A Fahmy + Show 8 more

Open Access

https://doi.org/10.3390/pharmaceutics12111059

Copy DOI

Journal: Pharmaceutics	Publication Date: Nov 6, 2020
Citations: 51	License type: CC BY 4.0

Affiliation: King Abdulaziz University, Jamia Hamdard

Abstract

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 Cmax 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.

Highlights

Acquired immunodeficiency syndrome (AIDS), a pandemic and perhaps the deadliest malady has claimed more than 39 million lives up until the year 2014
As per the UNAIDS (The Joint United Nations Program on human immunodeficiency virus (HIV)/AIDS) data, India in 2017 witnessed 2.1 million individuals affected with AIDS, 69,000 deaths, 88,000 new HIV infections, 0.2% adult HIV prevalence, and 56% adults and 33% children were on antiretroviral therapy [2]
The causative organism of AIDS is the human immunodeficiency virus (HIV), which debilitates the immune system by triggering the radical loss and dysregulation of the macrophages and CD4+T lymphocytes [3]

Summary

Introduction

Acquired immunodeficiency syndrome (AIDS), a pandemic and perhaps the deadliest malady has claimed more than 39 million lives up until the year 2014. The chronic administration of HAART, which is a combination of antiretroviral (ARV) drugs, proved quite effective in diminishing the viral burden and controlling its replication and transmission thereby assuring a long and productive life to the affected patients. The therapy lacked in offering a complete annihilation of the virus from the body owing to the existence of HIV in the anatomical reservoirs like the central nervous system (CNS), lymphatic system, lung, and liver. The virus in these reservoirs becomes latent and the presence of anatomical barriers limit the access to ARVs [5,6]. The ineptitude of the systemically administered ARVs to traverse the blood–brain barrier (BBB) makes the brain one of the predominant HIV reservoirs in the affected patients [7]

Methods

Results

Discussion

Conclusion