Formulation of PEGylated solid lipid nanoparticles for improving bioavailability of pravastatin: Optimization, ex vivo, and in vivo studies

Objective: Pravastatin (PV) is a BCS class III drug having low bioavailability. The objective of the present work was to formulate Pravastatin(PV) loaded solid lipid nanoparticles (PV-SLNs) and PV loaded PEGylated SLNs (PV-P-SLNs) for improving oral bioavailability. Methods: The SLNs were prepared using W/O/W emulsification method and optimized the formulation using 32 factorial design. The optimized formulation was coated with PEG 4000 monostearate. The ex vivo permeation study was carried out using rat ileum. The translocation of SLNs was examined to assess their accumulation using Rhodamine B fluorescent marker. In vivo, pharmacokinetics potential of PV-P-SLNs was evaluated, comparing it to PV-SLNs and PV solutions. Results :The particles size, % entrapment efficiency, and % drug release of the optimized formulation were found 291.4 +/- 7.8 nm, 66.15 +/- 1.8%, and 85.13 +/- 2.9% respectively. The Korsmeyer-Peppas model confirmed the drug release from lipid matrix followed fickian diffusion (n < 0.50). The ex vivo permeation study revealed 4 +/- 0.19 times more permeability (Papp= 3 x 10-6 cm/min) of PV-P-SLNs and 2.66 +/- 0.13 times more permeability of PV-SLNs (Papp = 2 x 10-6 cm/min) compared to PV solution (Papp = 0.75 x 10-6 cm/min). The in vivo bioavailability study revealed PV-P-SLNs showed 8.58 times more bioavailable compared to PV solutions. The pharmacodynamics studies demonstrated that the PV-P-SLNs was more effective in treating hyperlipidemia than PV solution based on blood analysis. Conclusions: Thus, it can be concluded that, PV-P-SLNs formulation successfully improved its pharmacokinetic profile, suggesting a promising approach for enhancing its therapeutic performance.