Tunable Two-Compartment On-Demand Sustained Drug Release Based on Lipid Gels

Abstract

The binary-lipid system of soybean phosphatidylcholine (SPC) and glycerol dioleate (GDO) can hydrate to gels on contacting with aqueous mediums, which has emerged as a versatile and promising delivery matrix for extended drug release applications. In the present work, we have characterized the gelation process of this SPC/GDO lyotropic gel (SGLG) system by rheology and evaluated the drug release profiles from the SGLG formulations with different SPC/GDO mass ratios. Our study has demonstrated that simply adjusting the SPC/GDO mass ratio can tune the lipid gelation behavior and modulate the drug release profiles. More importantly, the drug release from the SGLG formulations follows a two-compartment (fast and slow release compartments) release kinetics that has not been reported before. We posit that the fast release compartment corresponds to the passive diffusion of the drug during the early stage of the gel formation. After the boundary gel phase generation, the drug release is then dominated by the slow diffusion process from SGLG. The pharmacokinetic studies in rats match well with the in vitro studies, suggesting that the binary-lipid formulation is an excellent candidate for on-demand sustained drug delivery system.