McCormack B, Gregoriadis G
Centre for Drug Delivery Research, School of Pharmacy, University of London, U.K.
J Drug Target. 1994;2(5):449-54. doi: 10.3109/10611869408996821.
A novel concept in drug delivery discussed here, takes advantage of certain properties of the drug "containers" cyclodextrins and liposomes to combine them into a single system thus circumventing problems associated with both systems. The concept, entailing entrapment of water-soluble cyclodextrin-drug inclusion complexes in liposomes, would allow accommodation of insoluble drugs in the aqueous phase of vesicles. This 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 targeting 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 and entrapped into multilamellar liposomes by the dehydration-rehydration 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 considerable portions of the drugs were found to remain associated with the carrier in the presence of plasma.
本文讨论的一种药物递送新方法，利用了药物“载体”环糊精和脂质体的某些特性，将它们组合成一个单一系统，从而规避了与这两种系统相关的问题。该方法是将水溶性环糊精 - 药物包合物包裹在脂质体中，这将使不溶性药物能够容纳在囊泡的水相中。这有可能将药物与脂质的质量比提高到高于传统将药物掺入脂质相所达到的水平，扩大适合包封的不溶性药物范围，例如包括膜破坏剂，使复合物能够靶向特定部位并降低毒性。在本研究中，制备了羟丙基 - β - 环糊精与脱氢表雄酮、视黄醇和视黄酸的可溶性包合物，并通过脱水 - 再水化程序将其包裹在多层脂质体中。然后将含有复合物的脂质体暴露于血浆中。结果表明，复合物包裹到脂质体中取决于所用的脂质组成。在血浆存在的情况下，几乎所有的环糊精和相当一部分药物都与载体保持结合。
