Preparation of GBE50 oral proliposome and determination of its physicochemical properties

Aim: To prepare oral proliposomal delivery system of GBE50 and evaluate its physicochemical properties. Methods: GBE50 oral proliposomes were prepared by revese-phase evaporation method. RP-HPLC method with mobile phase for determination the main constituents in GBE50 oral liposomes was established. Orthogonal test design was used to optimize the liposome formulation. The particle size, zeta potential, entrapment efficiency and loading amount were evaluated. The physical stability was determined by measuring the release rate of liposome suspensions through pH 1.2 hydrochloric acid and pH 6.8 PBS. The cumulative release percentage of liposome suspension was tested in pH 1.2 hydrochloric acid solution, pH 6.8 PBS and pH 7.4 PBS. Results: The lowest determination concentrations of quercetin, kaempferol and isohamnetin were 20 ng·mL^-1, respectively, with more than 20 000 number of theoretical plates. The proliposome loading amount was 10.6% ± 2.9% and the entrapment efficiency of quercetin, kaempferol and isohamnetin was 83.1% ± 2.1%, 69.0% ± 3.5%, 67.5% ± 4.9%, respectively, with mean particle size (238.8 ± 12.2) nm. 5% mannitol(5 g mannitol: 100 mL liposome) was used as supporting carrier for liposome lyophilization. The proliposome showed a superordinary stability in pH 1.2 hydrochloric acid and pH 6.8 PBS. Main constituents of GBE50 in vitro drug release were all consistent with Higuchi dynamic equation. Conclusion: Entrapment efficiency and loading amount of GBE50 oral liposomes are both good. This is expected to highly improve the oral bioavailability of GBE50 new dosage forms.