Pamam dendrimer vitamin conjugate for delivery of anticancer agents

Abstract

Targeted delivery of cytotoxic drugs to malignant tumors may overcome the limitations associated with the anticancer agents and improve the pharmacokinetic profile of these drugs resulting in augmented patient compliance. Therefore, the present work is envisaged to selectively deliver the paclitaxel and methotrexate to the ovarian cancer cells by encapsulating them in a surface modified i.e. Biotinylated PAMAM-G4 dendrimers. As the PAMAM-G4 dendrimers are inherently cytotoxic in nature they provide a synergistic anticancer activity along with the solubility enhancement and high drug loading capacity. Hence, PAMAM-G4 was selected as a smart drug carrier. The active targeting approach was employed by modifying the surface groups of PAMAM-G4 with Vitamin H i.e. Biotin as the specific receptor for biotin are overexpressed in cancerous cells. newlineThe overall work demonstrated that the prepared paclitaxel and methotrexate loaded Biotinylated PAMAM-G4 dendrimeric formulations showed particle size in the range of 100 190 nm with good polydispersityindex of 0.127 and zeta potential of 21.43 mV showcasing a stable nano formulation. The drug loading of approximately 35 % for PTX and 21.5% for MTX. The in vitro drug release profile demonstrated controlled release up to 96 hours in which approximately 50 percentage drug was released in first 24 hours. The release kinetic models suggested the drug release is in accordance to first order release pattern. In vitro cytotoxicity assessment proved that the PTX and MTX loaded PAMAM-G4 formulations are comparatively more cytotoxic towards HeLa cells as compared to pure drugs. The in vivo pharmacokinetic data demonstrated higher AUC for the biotinylated formulations as compared to the pure drugs indicating higher bioavailability. newline