Allen T M
Department of Pharmacology, University of Alberta, Edmonton, Canada.
Drugs. 1998 Nov;56(5):747-56. doi: 10.2165/00003495-199856050-00001.
Liposomes are versatile drug carriers which can be used to solve problems of drug solubility, instability and rapid degradation. Both hydrophilic and hydrophobic drugs can be associated with liposomes and special techniques have been developed for the efficient loading of weak acids and weak bases into liposomes. Liposomes can function as sustained release systems for drugs and the rate of release can be manipulated. Advantage can be taken of the substantial changes in pharmacokinetics which often accompanies the association of drugs with liposomes. New formulations of liposomes, sterically stabilised with substances like surface-grafted polyethylene glycol have circulating half-lives in humans of up to 2 days. These long circulation times allow concentration of liposomal drug in regions of increased vascular permeability like solid tumours an decreased delivery of drug to normal tissues. Alterations of the biodistribution of drugs, when they are liposomes-associated, in general leads to significant overall decreases in drug toxicity but can also increase toxicity in some tissues. The use of targeting ligands to increase the selectivity of delivery of liposomal drugs to target tissues is currently under development. An understanding of how liposome association can alter drug properties can lead to their rational development in the treatment of many diseases.
脂质体是多功能药物载体，可用于解决药物溶解性、稳定性和快速降解等问题。亲水性和疏水性药物均可与脂质体结合，并且已经开发出了将弱酸和弱碱高效载入脂质体的特殊技术。脂质体可作为药物的缓释系统，其释放速率可以控制。药物与脂质体结合后，药代动力学通常会发生显著变化，可加以利用。用诸如表面接枝聚乙二醇等物质进行空间稳定化处理的新型脂质体配方，在人体中的循环半衰期可达2天。这些较长的循环时间使得脂质体药物能够在血管通透性增加的区域（如实体瘤）富集，同时减少药物向正常组织的递送。药物与脂质体结合后，其生物分布的改变通常会导致药物毒性总体显著降低，但在某些组织中也可能增加毒性。目前正在研发使用靶向配体来提高脂质体药物向靶组织递送的选择性。了解脂质体结合如何改变药物特性有助于合理开发脂质体用于治疗多种疾病。
