Co-encapsulation of metformin hydrochloride and reserpine into flexible liposomes: Characterization and comparison of in vitro release profile

Abstract

In the present study, we obtained small unilamellar vesicles by adopting the thin hemispherical lipid-film (containing Reserpine) technique for the encapsulation of Metformin hydrochloride (MET) and Reserpine (RES) together. The nano-sized flexible liposomes were prepared by 2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC), cholesterol and Tween-80 in different mole ratios. Saturation solubility of RES in water with and without Tween-80 was determined before formulation development. The resulting liposomes were characterized in terms of vesicular-size, polydispersity, zeta-potential, vesicles morphology, percent encapsulation and loading of MET and RES. The optimized liposome was subjected to deformability test, in vitro drug release study and storage stability at 4 and 25 °C temperatures for 2-months. The prepared liposomes were shown 81–184 nm vesicular-size with polydispersity-index of 0.224–0.307 and the zeta-potentials were −6.87 to −15.33 mV. The liposomes encapsulated 38–46% of MET and 61–69% of RES, while 17.38–20.39% of MET and 2.92–3.33% of RES were loaded, depending upon the molar ratios of the excipients especially the amounts of DPPC and cholesterol. Transmission electron microscopy revealed the unilamellar vesicular structure of the optimized liposome (L1) with proper dispersion of the vesicles. Deformability (12.61%) of L1 revealed its talent in retaining its size even after forceful passing of these vesicles through the polycarbonate membrane. Cumulative release data (65% MET and 56% RES) indicated the sustained release of both the drugs till 12 h by following Korsmeyer-Peppas model. Non-significant (p < 0.05) changes in the physical characteristics of L1, suggested its storage stability at 4 °C and 25 °C for 2-months.