Ouyang C, Choice E, Holland J, Meloche M, Madden T D
Department of Pharmacology, University of British Columbia, Vancouver, Canada.
Transplantation. 1995 Nov 15;60(9):999-1006.
A number of previous studies have examined the application of liposomes as carriers for the immunosuppressive agent cyclosporine. These studies, however, have generated equivocal results, particularly with regard to the therapeutic properties of such systems. In the present work, we have characterized cyclosporine incorporation into well defined liposomes, large unilamellar vesicles, and have examined the stability of drug association. Contrary to some earlier reports, we show that only modest levels of cyclosporine can be accommodated in the liposomal membrane and that the extent of drug incorporation is greatly reduced as the bilayer cholesterol content is increased. Furthermore, we demonstrate that cyclosporine, despite its hydrophobic character, can rapidly exchange between vesicles. This raises the possibility that, after i.v. administration, drug migration to other blood components might negate the potential benefits arising from liposomal delivery. In a companion paper, therefore (Choice et al., Transplantation, 1995, this issue), we have followed the pharmacokinetics and biodistribution of liposomal cyclosporine in a study that examined the behavior of both the drug and the liposomal carrier.
此前已有多项研究探讨了脂质体作为免疫抑制剂环孢素载体的应用。然而，这些研究结果并不明确，尤其是在这类体系的治疗特性方面。在本研究中，我们对环孢素掺入明确界定的脂质体（大单层囊泡）进行了表征，并研究了药物结合的稳定性。与一些早期报告相反，我们发现脂质体膜仅能容纳适量水平的环孢素，并且随着双层胆固醇含量的增加，药物掺入程度会大幅降低。此外，我们证明，尽管环孢素有疏水性，但它能在囊泡之间快速交换。这增加了一种可能性，即静脉注射给药后，药物向其他血液成分的迁移可能会抵消脂质体递送带来的潜在益处。因此，在一篇配套论文中（乔伊斯等人，《移植》，1995年，本期），我们在一项研究中追踪了脂质体环孢素的药代动力学和生物分布，该研究考察了药物和脂质体载体的行为。
