Pharmaceutics Research Laboratory, Department of Pharmaceutical Sciences, Dr Hari Singh Gour University, Sagar, India.
J Microencapsul. 2009 Jun;26(4):287-96. doi: 10.1080/02652040802312572.
A major problem associated with conventional leukaemia chemotherapy is the development of resistance that can be surmounted well by combination chemotherapy. The objective of the present investigation is to report a novel technology to load two anti-leukaemic drugs of choice simultaneously inside the PAMAM dendrimer. Under optimized conditions of pH and dialysis time, one molecule of PAMAM dendrimer was found to be capable of entrapping 27.02 ± 0.51 and 8.00 ± 0.46 molecules of Methotrexate and all-trans Retinoic acid (ATRA), respectively. The simultaneous in-vitro release profiling of the loaded drugs was studied at pH 4, 7.4 and 10. The release kinetics was found to be governed by degree of dendrimer protonation, with more sustained and controlled behaviour at pH 7.4. Terminal loading of dendrimer with less haemolytic bioactive (ATRA) reduced the haemolytic toxicity of the dendrimer formulation. A cytotoxicity study was performed on HeLa cell lines by MTT assay, wherein after 72 h, the dual-drug loaded dendrimer was found to be more efficient (IC(50) 0.5 µM) as compared to that of the free drug combination (IC(50) 0.75 µM).
常规白血病化疗的一个主要问题是耐药性的产生，联合化疗可以很好地克服这一问题。本研究的目的是报道一种将两种选择的抗白血病药物同时负载到 PAMAM 树状大分子内部的新技术。在优化的 pH 值和透析时间条件下，发现一个 PAMAM 树状大分子分子能够分别包封 27.02±0.51 和 8.00±0.46 个甲氨蝶呤和全反式维甲酸（ATRA）分子。在 pH 4、7.4 和 10 下研究了负载药物的同时体外释放情况。释放动力学由树突状大分子的质子化程度控制，在 pH 7.4 时具有更持续和更受控的行为。通过末端负载具有较低细胞毒性的生物活性（ATRA）的树突状大分子，降低了树突状大分子制剂的溶血毒性。通过 MTT 法对 HeLa 细胞系进行了细胞毒性研究，在 72 小时后，与游离药物组合（IC50 为 0.75 μM）相比，负载双药物的树突状大分子更为有效（IC50 为 0.5 μM）。
