Formulation Design, Optimization, and Evaluation of Solid Lipid Nanoparticles Loaded With an Antiviral Drug Tenofovir Using Box-Behnken Design for Boosting Oral Bioavailability

Abstract

Purpose: The current study aimed to improve the oral bioavailability of tenofovir (TNF), an antihuman immunodeficiency viral (HIV) drug, by integrating it into solid lipid nanoparticles (SLNs), an emerging lipid formulation. Method: The suggested SLNs were generated utilizing the microemulsion process, using Compritol 888 ATO. A Box-Behnken experimental design was attempted to analyze the impact of critical quality attributes (CQAs), such as lipid and surfactant content and homogenization duration on response metrics such as particle size (PS) and percentage entrapment. The prepared SLNs were assessed for entrapment efficiency, zeta potential (ZP), PS, polydispersity index, and in vitro drug release. Moreover, ex vivo permeation tests employing goat intestinal sacs, solid-state characterization by DSC and PXRD, surface morphology by SEM, and in vivo pharmacokinetic evaluation using albino Wistar rats were conducted. Results: The research findings demonstrated that a formulation composed of 5.5% lipid and 2% surfactant had a comparatively smaller PS (449.90 ± 4.79 nm), a narrow size distribution (0.304 ± 0.004), and strong stability with an entrapment efficiency of 83.13 ± 6.34% and a negative ZP (-18.10 ± 2.35 mV). According to in vitro drug release experiments, first-order kinetics were followed and 99% of the medication was released over the time course of 24 h. In albino Wistar rats, an in vivo pharmacokinetic analysis of the optimized formulation (F10) showed a 12.4-fold improvement in bioavailability over pure TNF solution. Conclusion: This study suggests the potential of SLNs in overcoming bioavailability issues, particularly low permeability, gut metabolism, and P-gp efflux transport.

Keywords: Compritol 888 ATO; nanocarriers; risk assessment; solid lipid nanoparticles; tenofovir.