Exploring dendrimer towards dual drug delivery: pH responsive simultaneous drug-release kinetics

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 (IC50 0.5 mu M) as compared to that of the free drug combination (IC50 0.75 mu M).