Rilpivirine-loaded solid lipid nanoparticles: preparation, characterization, and in vivo evaluation for enhancing oral bioavailability

Objective(s): This study aimed to improve the oral bioavailability of Rilpivirine by creating and testing Rilpivirine solid lipid nanoparticles (SLNs) to determine the impact of drug delivery on pharmacokinetics following oral treatment in Wistar rats.Materials and Methods: Solid lipid nanoparticles (SLNs) were fabricated using a high-pressure homogenization technique, after which they were evaluated for their physicochemical properties including particle size, morphology, zeta potential, encapsulation efficiency as well as their in vitro release behaviour, ex vivo permeability, and in vivo pharmacokinetics in Wistar rats. To further understand how SLNs are taken up through the lymphatic system, an ex vivo study was carried out using an everted rat intestinal sac model.Results: The resulting SLNs were spherical, showing an average particle size of ۷۴.۴۵ ± ۰.۸۴ nm with a PDI of ۰.۲۷, zeta potential -۱۷.۴۹ ± ۰.۸۲ mV, and an entrapment efficiency of ۶۲.۹ ± ۱.۲%. The SLN formulation demonstrated ۸۴% drug release over a ۲۴-hour period. In an ex vivo study using everted rat intestine, the SLN's apparent permeability was ۳۴.۲ × ۱۰-۶ at ۳۷ ± ۰.۵ °C without chlorpromazine. This value decreased to ۱۴.۶ × ۱۰-۶ when chlorpromazine was present. Pharmacokinetic studies in rats showed the SLN formulation's AUC was ۱.۰۴ times higher than that of the pure drug suspension. Conversely, adding the lymphatic uptake inhibitor chlorpromazine reduced the SLN's AUC by ۰.۵۲-fold. The in vivo pharmacokinetic data was assessed by Dunnett's test, which indicated a significant difference (p < ۰.۰۵) between the RLV SLNs and the plain RLV drug.Conclusion: Employing SLNs as a delivery vehicle appears to be a viable method for boosting the therapeutic efficacy of rilpivirine. A key reason is that SLN lymphatic uptake is important for avoiding hepatic first-pass metabolism.

کلیدواژه ها:

Rilpivirine ، Bioavailability ، Lymphatic uptake ، Solid lipid nanoparticles ، permeability ، solubility