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.

Terbinafine hydrochloride, although one of the prominent antifungal agents, suffers from low drug permeation owing to its hydrophobic nature. The approach of nanosponge formulation may thus help to resolve this concern. Thus, the present research was envisioned to fabricate the nanosponge hydrogel of terbinafine hydrochloride for topical delivery since nanosponge augments the skin retentivity of the drug. The optimized formulation was obtained using Box Behnken Design. The dependent and independent process parameters were also determined wherein polyvinyl alcohol (%), ethylcellulose (%), and tween 80 (%) were taken as independent process parameters and particle size, polydispersity index (PDI), and entrapment efficiency (EE) were the dependent parameters. The nanosponge was then incorporated into the hydrogel and characterized. In-vitro drug release from the hydrogel was 90.20 ± 0.1% which was higher than the drug suspension and marketed formulation. In vitro permeation potential of the developed formulation through rat skin showed a flux of 0.594 ± 0.22 µg/cm²/h while the permeability coefficient was 0.059 ± 0.022 cm/s. Nanosponge hydrogel was evaluated for non-irritancy and antifungal activity against C. albicans and T. rubrum confirming the substantial outcome. Tape stripping studies exhibited ten times stripping off the skin quantified 85.6 ± 0.21 μg/cm². The confocal analysis justified the permeation potential of the prepared hydrogel. The mean erythemal score was 0.0, confirming that the prepared hydrogel did not cause erythema or oedema. Therefore, based on results obtained, nanosponge hydrogel formulation is a potential carrier for efficient topical delivery of terbinafine hydrochloride.

The journal retracts the article “Development and Evaluation of Polymeric Nanosponge Hydrogel for Terbinafine Hydrochloride: Statistical Optimization, In Vitro and In Vivo Studies”