Dendritic Cisplatin as a Nanodevice for Treatment of Ovarian Cancer
V.K. Yellepeddi, A. Kumar, S. Palakurthi
Texas A&M HSC College of Pharmacy, US
Keywords: Biotinylated PAMAM dendrimers, Cisplatin, Biotin-PAMAM-cisplatin (BPC)
Abstract:Polyamidoamine (PAMAM) dendrimers are a class of hyperbranched nanoscale hydrophilic polymers which have easily tailorable surface moieties and have found several applications including carriers for genes and delivery of anti cancer drugs. As our earlier results showed increase uptake of biotin dendrimers by ovarian cancer cells we hypothesize that biotinylated dendrimers loaded with cisplatin will be specific to the ovarian cancer. The Biotin-PAMAM-Cisplatin (BPC) nanoscaffolds were synthesized and encapsulation efficiency, in vitro release profile, in vitro cellular uptake and single dose pharmacokinetics on rats was performed using HPLC as quantification technique. The cytotoxicity of cisplatin-dendrimer conjugates was compared with unconjugated cisplatin using MTT (Methylthiazole tetrazolium) assay in various ovarian cancer cell lines OVCAR-3, SKOV, A2780 (wild-type) and CP 70(Cisplatin resistant). Preliminary single dose intraperitoneal pharmacokinetics was performed on male wistar rats. Statistical analysis of the data was performed using student’s t test and p<0.05 was considered significant. The results indicated that cisplatin encapsulated with biotin dendrimers would result in better cytotoxic activity, effective with cisplatin resistant cell lines and can be used to target cancer more effectively. Preliminary pharmacokinetics indicated a 17% increase in Cmax¬ with biotinylated dendrimers (p<0.05).