Salem Isam Ismail, Düzgünes Nejat
Department of Microbiology, University of the Pacific, 2155 Webster Street, San Francisco, CA 94115, USA.
Int J Pharm. 2003 Jan 16;250(2):403-14. doi: 10.1016/s0378-5173(02)00552-5.
Cyclodextrins and liposomes have been used in recent years as drug delivery vehicles, improving the bioavailability and therapeutic efficacy of many poorly water-soluble drugs. In this study, we used two approaches to enhance the availability of the poorly water-soluble antibiotic, clarithromycin, by inclusion complex formation and by liposome-encapsulation. We examined the efficacies of these formulations against Mycobacterium avium complex (MAC) in human peripheral blood monocyte-derived macrophages. The water solubility of clarithromycin was enhanced by about 700-fold by complexation with cyclodextrin. The use of a rapid radiometric (BACTEC) method for the detection of MAC growth and susceptibility showed identical MICs against MAC for both the free and complexed drug. The anti-MAC efficacy of the cyclodextrin complex of clarithromycin in macrophages was slightly lower than the free drug, probably due to the high stability of the inclusion complex. At higher drug concentrations, Liposome-encapsulated clarithromycin was slightly more effective against intracellular MAC growth than the free drug.
近年来，环糊精和脂质体已被用作药物递送载体，提高了许多难溶性药物的生物利用度和治疗效果。在本研究中，我们采用两种方法，通过形成包合物和脂质体包封来提高难溶性抗生素克拉霉素的利用率。我们在人外周血单核细胞衍生的巨噬细胞中检测了这些制剂对鸟分枝杆菌复合群（MAC）的疗效。通过与环糊精络合，克拉霉素的水溶性提高了约700倍。使用快速放射测量法（BACTEC）检测MAC生长和药敏性显示，游离药物和络合药物对MAC的最低抑菌浓度相同。克拉霉素环糊精复合物在巨噬细胞中的抗MAC疗效略低于游离药物，这可能是由于包合物的高稳定性所致。在较高药物浓度下，脂质体包封的克拉霉素对细胞内MAC生长的抑制作用略强于游离药物。
