Transferrin coupled vesicular system for intracellular drug delivery for the treatment of cancer: development and characterization.

Objectives: In the present study attempt has been made to enhance the selective tumor cell killing in mouse xenograft model using DQAsomes as a mitochondriotropic carrier and transferrin (Tf) as a ligand to target tumor cells.

Methods: Tf modified DQAsomes (Tf-DQAsomes) were prepared by incubating preformed paclitaxel loaded DQAsomes with Tf in the presence of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride. Developed systems were characterized for size and size distribution, entrapment efficiency, and in vitro drug release. Fluorescence microscopy and flow cytometry were performed to evaluate cellular uptake of the carriers. Antitumor activity was determined using HeLa cells. In vivo therapeutic efficacy was determined in xenograft mouse model.

Key Findings: Uptake studies demonstrated that Tf-DQAsomes result in higher fluorescence intensity to the cancer cells as compared to plain DQAsomes. Tf-DQAsomes exhibited better antitumor activity in vitro as compared to plain DQAsomes and paclitaxel solution. In vivo biodistribution study revealed that paclitaxel concentration in the tumor was much higher in the case of Tf-DQAsomes as compared to plain DQAsomes and paclitaxel solution; however in other organs it was much lower than the latter two formulations. Tf-DQAsomes exhibited significant antitumor activity in the mouse xenograft model.

Conclusions: The finding demonstrated that Tf conjugated DQAsomes can effectively be delivered to the tumor in vivo and exhibit significant antitumor activity.