Lipid core-chitosan shell hybrid nanoparticles for enhanced oral bioavailability of sorafenib

Limited aqueous solubility is a major hurdle resulting in poor and variable oral bioavailability, high doses, side effects, and the suboptimal therapeutic efficacy of sorafenib (SRF). In this study, we developed SRF-loaded solid lipid nanoparticles (SRF-SLNs) and lipid core-chitosan shell hybrid nanoparticles (CS-SRF-SLNs) to improve the oral absorption of SRF. SRF-SLNs were prepared using a stearyl alcohol core stabilized with a surfactant mixture, followed by surface decoration with chitosan to form CS-SRF-SLNs. The developed SRF-SLNs and CS-SRF-SLNs displayed uniform and well-separated spherical particles with small particle size (112.2 and 124.6 nm), low PDI (0.114 and 0.148), adequate zeta potential (-18.6 and +21.2 mV) and high encapsulation efficiency (92.0 and 91 %). Thermal and crystallinity studies (DSC and PXRD) confirmed the successful incorporation of SRF into the lipid matrix and its conversion to the amorphous state. The CS-SRF-SLNs demonstrated sustained SRF release in simulated gastric and intestinal fluids with improved aqueous solubility. Following oral administration to rats, CS-SRF-SLNs significantly improved SRF bioavailability compared with SRF-SLNs and SRF dispersion. Collectively, CS-SRF-SLNs were found to be superior to SRF-SLNs owing to their better sustained-release profile and pharmacokinetic parameters, thereby demonstrating their usefulness for oral delivery by minimizing the solubility-related issues of SRF.