ENTRAPMENT OF CYCLODEXTRIN DRUG COMPLEXES INTO LIPOSOMES - POTENTIAL ADVANTAGES IN DRUG-DELIVERY

A novel concept in drug delivery discussed here, takes advantage of ce rtain properties of the drug ''containers'' cyclodextrins and liposome s to combine them into a single system thus circumventing problems ass ociated with both systems. The concept, entailing entrapment of water- soluble cyclodextrin-drug inclusion complexes in liposomes, would allo w accommodation of insoluble drugs in the aqueous phase of vesicles. T his would potentially increase the drug to lipid mass ratio to levels above those attained by conventional drug incorporation into the lipid phase, enlarge the range of insoluble drugs amenable to encapsulation to include, for instance, membrane destabilizing agents, allow target ing of complexes to specific sites and reduce toxicity. In the present work, soluble inclusion complexes of hydroxypropyl-beta-cyclodextrin with dehydroepiandrosterone, retinol and retinoic acid were prepared a nd entrapped into mutlilamellar liposomes by the dehydration-rehydrati on procedure. Complex-containing liposomes were then exposed to blood plasma. Results show that complex entrapment into liposomes depends on the lipid composition used. Nearly all of the cyclodextrin and consid erable portions of the drugs were found to remain associated with the carrier in the presence of plasma.