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

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.

Ezetimibe-Loaded Nanostructured Lipid Carrier Based Formulation Ameliorates Hyperlipidaemia in an Experimental Model of High Fat Diet

“…Prajapati et al, described that the objective of preparing NLCs was to avoid its first-pass metabolism by way of lymphatic uptake [ 19 ]. Also, we assume that the efficiency of ezetimibe could be improved by loading the drug in nanostructured lipid carriers as previously reported by Khan et al [ 20 ]. In our previous studies (Agrawal et al [ 21 ]) we also emphasized that by using nanostructured lipid carriers the efficiency and bioavailability of drugs could be improved significantly and it also helps to avoid first pass metabolism.…”

Lipid Nanocarriers for Anti-HIV Therapeutics: A Focus on Physicochemical Properties and Biotechnological Advances

“…For example, liposomes have been documented as capable to increase half-lives of d4T, AZT, ddI, and RTV [ 13 , 14 , 15 , 16 , 20 , 79 , 80 ] ( Table 3 ). Finally, many ARTs have a limited bioavailability in the brain, but the ability of lipid nanocarriers to mediate the brain delivery of ARVs has been widely documented, either for liposomes that potentially improve brain accumulation of AZT [ 81 ], or for SLN used for improving brain bioavailability of ATV, SQV, EFV, NVP and DRV [ 64 , 65 , 82 , 83 , 84 , 85 ], or NLC used as carriers of LPV, ATV, ETR [ 83 , 86 , 87 ] and NE improving brain accumulation of SQV and IDV [ 88 , 89 , 90 ]. From these studies it is worthwhile highlighting the SLN developed for EFV delivery that attained 150 folds more brain targeting delivery than the free drug [ 84 ]; the NLC for ATV delivery that attained 2.75 folds higher C max at the brain and 4 folds higher brain bioavailability [ 86 ] and NE as a carrier of IDV that assured specific brain accumulation of the drug [ 89 ] ( Table 3 , Table 4 and Table 5 ).…”

“…Typically, only drugs with logP values between 1 and 3 have favorable oral absorption profiles [ 138 ]. Most ARV drugs are outside this range ( Table 3 , Table 4 and Table 5 ), being either extremely hydrophilic (e.g., ddI [ 97 ] and AZT [ 121 ]) or highly lipophilic (e.g., LPV [ 66 , 71 , 83 , 109 ], RTV [ 110 ], EFV [ 16 , 75 , 129 ], SQV [ 90 , 126 ], EFZ [ 131 ] and ATV [ 86 ]). Therefore, lipid-based nanocarriers may help ARV drugs achieving a balanced lipophilic/hydrophilic nature.…”

Lipid Nanocarriers for Anti-HIV Therapeutics: a Focus on Physicochemical Properties and Biotechnological Advances

“…For example, liposomes have been documented as capable to increase half-lives of d4T, AZT, ddI and RTV [13][14][15][16]20,79,80] (Table 3). Finally, many ART have a limited bioavailability in the brain, but the ability of lipid nanocarriers to mediate the brain delivery of ARVs has been widely documented, either for liposomes that potentially improve brain accumulation of AZT [81], or for SLN used for improving brain bioavailability of ATV, SQV, EFV, NVP and DRV [64,65,[82][83][84][85], or NLC used as carriers of LPV, ATV, ETR [83,86,87] and NE improving brain accumulation of SQV and IDV [88][89][90]. From these studies it is worthwhile highlighting the SLN developed for EFV delivery that attained 150 folds more brain targeting delivery than the free drug [84]; the NLC for ATV delivery that attained 2.75 folds higher Cmax at brain and 4 folds higher brain bioavailability [86] and NE as carrier of IDV that assured specific brain accumulation of the drug [89] (tables 3 to 5).…”

“…Typically, only drugs with logP values between 1 and 3 have favorable oral absorption profiles [149]. Most ARV drugs are outside this range (Tables 3 to 5), being either extremely hydrophilic (e.g., ddI [150] and AZT [130]) or highly lipophilic (e.g., LPV [66,71,83,112], RTV [114], EFV [16,75,140], SQV [90,136], EFZ [142] and ATV [86]). Therefore, lipid-based nanocarriers may help ARV drugs achieving a balanced lipophilic/hydrophilic nature.…”