Dg. Fatouros et al., Liposomes encapsulating prednisolone and prednisolone-cyclodextrin complexes: Comparison of membrane integrity and drug release, EUR J PH SC, 13(3), 2001, pp. 287-296
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.