Banerjee Jayati, Hanson Andrea J, Gadam Bhushan, Elegbede Adekunle I, Tobwala Shakila, Ganguly Bratati, Wagh Anil V, Muhonen Wallace W, Law Benedict, Shabb John B, Srivastava D K, Mallik Sanku
Department of Pharmaceutical Sciences, Department of Chemistry, Biochemistry and Molecular Biology, North Dakota State University, Fargo, North Dakota 58108, USA.
Bioconjug Chem. 2009 Jul;20(7):1332-9. doi: 10.1021/bc9000646.
Liposomes have been widely used as a drug delivery vehicle, and currently, more than 10 liposomal formulations are approved by the Food and Drug Administration for clinical use. However, upon targeting, the release of the liposome-encapsulated contents is usually slow. We have recently demonstrated that contents from appropriately formulated liposomes can be rapidly released by the cancer-associated enzyme matrix metalloproteinase-9 (MMP-9). Herein, we report our detailed studies to optimize the liposomal formulations. By properly selecting the lipopeptide, the major lipid component, and their relative amounts, we demonstrate that the contents are rapidly released in the presence of cancer-associated levels of recombinant human MMP-9. We observed that the degree of lipid mismatch between the lipopepides and the major lipid component profoundly affects the release profiles from the liposomes. By utilizing the optimized liposomal formulations, we also demonstrate that cancer cells (HT-29) which secrete low levels of MMP-9 failed to release a significant amount of the liposomal contents. Metastatic cancer cells (MCF7) secreting high levels of the enzyme rapidly release the encapsulated contents from the liposomes.
脂质体已被广泛用作药物递送载体，目前，有超过10种脂质体制剂已获美国食品药品监督管理局批准用于临床。然而，在靶向给药时，脂质体包裹内容物的释放通常较为缓慢。我们最近证明，经适当配制的脂质体中的内容物可被癌症相关酶基质金属蛋白酶-9（MMP-9）快速释放。在此，我们报告我们为优化脂质体制剂所做的详细研究。通过适当选择脂肽、主要脂质成分及其相对含量，我们证明在存在癌症相关水平的重组人MMP-9时，内容物会快速释放。我们观察到脂肽与主要脂质成分之间的脂质不匹配程度深刻影响脂质体的释放曲线。通过使用优化的脂质体制剂，我们还证明分泌低水平MMP-9的癌细胞（HT-29）无法释放大量脂质体内容物。分泌高水平该酶的转移性癌细胞（MCF7）会迅速从脂质体中释放包裹的内容物。
