Preparation, characterization and pharmacokinetics of liposomes-encapsulated cyclodextrins inclusion complexes for hydrophobic drugs.

Liposomes-encapsulated indomethacin/cyclodextrins (IMC/ CD) inclusion complexes were prepared. The characteristics and pharmacokinetics of the combined system were investigated. The high drug entrapment values of 2.38 +/- 0.16 microg/mg and 2.48 +/- 0.12 microg/mg for liposomes-encapsulated IMC/ beta-CD and IMC/HP-beta-CD inclusion complexes were achieved, as only 1.60 +/- 0.09 microg/mg for conventional liposomes. Encapsulating IMC/CD inclusion complexes into liposomes resulted in a slow release of drug. Following intravenous administration, both liposomes-encapsulated inclusion complexes showed significantly improved AUC(0 - infinity) compared with that of conventional liposomes (p < 0.05). After intramuscular administration, C(max) has been increased to 5.21 +/- 1.14 microg x ml(-1) and 6.02 +/- 1.22 microg x ml(- 1) for liposomes-encapsulated IMC/ beta -CD and IMC/HP-beta -CD inclusion complexes, respectively, whereas only 2.43 +/- 0.69 microg x ml(- 1) for liposomes-encapsulated free drug (p < 0.01).