Liposomes encapsulating prednisolone and prednisolone-cyclodextrin complexes: Comparison of membrane integrity and drug release

Inclusion complexes of prednisolone (PR) with beta -cyclodextrin (beta -CD) and hydropropyl-beta -cyclodextrin (HP beta -CD) were formed by the solvat ion method, and were characterized by DSC, X-ray diffractometry and FT-IR s pectroscopy. PC liposomes incorporating PR as plain drug or inclusion compl ex were prepared using the dehydration-rehydration method and drug entrapme nt as well as drug release were estimated for all liposome types prepared. The highest PR entrapment value (80% of the starting material) was achieved for PC/Chol liposomes when the HP beta -CD-PR (2:1, mol/mol) complex was e ntrapped. The leakage of vesicle encapsulated 5,6-carboxyfluorescein (CF) w as used as a measure of the vesicle membrane integrity. As judged from our experimental results liposomes which encapsulate beta -CD-PR complexes are significantly less stable (when their membrane integrity is considered) com pared to liposomes of identical lipid compositions which incorporate plain drug or even (in some cases) non-drug incorporating liposomes, which were p repared and studied for comparison. Interestingly, liposomes which encapsul ate HP beta -CD-PR complexes, have very low initial CF latency values, indi cating that the leakage of CF is a process of very high initial velocity. I nteractions between lipid and cyclodextrin molecules may be possibly result ing in rapid reorganization of the lipid membrane with simultaneous fast re lease of CF molecules. The release of PR from liposomes was highest when th e drug was entrapped in the form of a complex with beta -CD. Nevertheless, the very high entrapment ability of PR in the form of HP beta -CD-PR comple xes in comparison to plain drug is a indubitable advantage of this approach . (C) 2001 Elsevier Science BN. All rights reserved.