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 solvation method, and were characterized by DSC, X-ray diffractometry and FT-IR spectroscopy. PC liposomes incorporating PR as plain drug or inclusion complex were prepared using the dehydration-rehydration method and drug entrapment 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 entrapped. The leakage of vesicle encapsulated 5,6-carboxyfluorescein (CF) was 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) compared to liposomes of identical lipid compositions which incorporate plain drug or even (in some cases) non-drug incorporating liposomes, which were prepared and studied for comparison. Interestingly, liposomes which encapsulate HP beta -CD-PR complexes, have very low initial CF latency values, indicating that the leakage of CF is a process of very high initial velocity. Interactions between lipid and cyclodextrin molecules may be possibly resulting in rapid reorganization of the lipid membrane with simultaneous fast release of CF molecules. The release of PR from liposomes was highest when the 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 complexes in comparison to plain drug is a indubitable advantage of this approach. (C) 2001 Elsevier Science BN. All rights reserved.