Development of a new topical system: Drug-in-cyclodextrin-in-deformable liposome

Abstract

A new delivery system for cutaneous administration combining the advantages of cyclodextrin inclusion complexes and those of deformable liposomes was developed, leading to a new concept: drug-in-cyclodextrin-in-deformable liposomes. Deformable liposomes made of soybean phosphatidylcholine (PC) or dimyristoylphosphatidylcholine (DMPC) and sodium deoxycholate as edge activator were compared to classical non-deformable liposomes. Liposomes were prepared by the film evaporation method. Betamethasone, chosen as the model drug, was encapsulated in the aqueous cavity of liposomes by the use of cyclodextrins. Cyclodextrins allow an increase in the aqueous solubility of betamethasone and thus, the encapsulation efficiency in liposome vesicles. Liposome size, deformability and encapsulation efficiency were calculated. The best results were obtained with deformable liposomes made of PC in comparison with DMPC. The stability of PC vesicles was evaluated by measuring the leakage of encapsulated calcein on the one hand and the leakage of encapsulated betamethasone on the other hand. In vitro diffusion studies were carried out on Franz type diffusion cells through polycarbonate membranes. In comparison with non-deformable liposomes, these new vesicles showed improved encapsulation efficiency, good stability and higher in vitro diffusion percentages of encapsulated drug. They are therefore promising for future use in ex vivo and in vivo experiments.