Abstract 3229: Thermo-responsive double packaged system for localized drug delivery for cancer treatment

Abstract

Abstract This research aims at developing a drug delivery system that will provide a plethora of benefits including cost effectiveness, reduction of toxicity and a control over the release of chemotherapeutics in Ovarian Cancer and Brain Tumor patients. We have designed a drug delivery system consisting of non-ionic surfactant vesicles (niosomes) packaged within a biodegradable, temperature and pH sensitive hydrogel (chitosan) network. Optimization of the release rates were accomplished by altering the molecular weight and cross-link density of the chitosan network and the size of the niosomes. Two chemotherapeutics Paclitaxel and Carboplatin were used for encapsulation. The interaction between niosome and chitosan were observed using Attenuated Total Reflectance- Fourier Transform Infrared (ATR-FTIR) spectroscopy. The drug delivery system was further investigated in human ovarian (OV2008) and human glioma (U373) cell lines. The concentration of the therapeutics used ranged from 0.04-0.4 µg/ml. Confocal imaging of the cells verified that the activity of the drugs remained intact within the niosome-chitosan drug delivery system and cell's toxicity was observed within two hours confirming cellular delivery of the drug. The effect of the niosome-chitosan without the chemotherapeutic drugs on normal cells was also examined indicating that this system is non-toxic. Our results showed that this route of drug delivery to the cancer cells was effective since microtubule stabilization, fragmentation of the nucleus, and condense morphology were noted. Moreover, the time release of the drugs can be finely controlled by varying the crosslinking ratio in the chitosan network from 3:1 (loose network which translates into high release) to 5:1 (tight network which translates into low release). In addition, this system is a liquid solution at room temperature and undergoes a change of phase to a soft, self-containing gel at physiological conditions. The system therefore, can be injected into a tumor site. The materials used to construct this system are low cost and biocompatible and provides a flexible method for drug delivery with applications to intracavitary ovarian cancer and glioma treatment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3229. doi:10.1158/1538-7445.AM2011-3229