Liposomal diltiazem HCl as ocular drug delivery system for glaucoma

Abstract

In this study, unilamellar liposomal vesicles of diltiazem HCl (DH) were prepared using either reversed phase evaporation (REV) or proliposome methods. Soya phosphatidylcholine (SPC) was used for preparing the liposomes, and the vesicles were rigidified using cholesterol (Chol) or cetyl alcohol (CA) in different molarities. The major differences in both the entrapment efficiency percent (EE%) and drug release were evaluated as a function of the method of preparation, Chol or CA contents, and charging lipids. Moreover, the morphology of the vesicles was confirmed by transmission electron microscopy. The effects of Chol or CA incorporation into the liposomes were discussed based on thermal analysis. The in vivo evaluation of liposomal DH was assessed using intra-ocular pressure (IOP), reducing effects in rabbit eyes. Liposomes prepared via REV exhibited higher EE% and lower release rates when compared with those prepared from proliposomes. The incorporation of either Chol or CA in the liposomes enhanced the EE% and decreased the release rates; however, Chol yielded higher results than CA. In addition, both dicetyl phosphate (DCP; negative charge inducer) and stearyl amine (SA, positive charge inducer) decreased the EE% and increased the DH release rate. The in vivo antiglaucoma effects of the liposomes were calculated according to the area above the IOP/Time curve, the maximum response and the time for the maximum response and were compared with effects of the DH solution. The results were in the following order: DH solution < SPC/CA (REV) < SPC/Chol/DCP(REV) < SPC/Chol (proliposomes) < SPC/Chol/SA(REV) < SPC/Chol (REV).