Abstract 5410: Enhanced targeting delivery to tumor cells using mucoadhesive chitosan and chlorotoxin

Abstract

Abstract Specific drug delivery to tumor cells without affecting normal cells remains a major challenge in cancer treatment. We present a localized drug delivery system with enhanced targeting ability consisting of non-ionic surfactant vesicles (niosomes) with chlorotoxin (CTX) embedded in a chitosan hydrogel. This system represents a novel approach in cancer therapy through the controlled and targeted delivery of drugs to tumor cells. We have found the specific accumulation of chitosan on the surface of ovarian epithelial carcinoma cells known to have high expression of mucin antigen MUC1, but not on the normal ovarian epithelial cells. This finding demonstrates the capability of chitosan to target tumor cells expressing MUC1. Similarly, the incorporation of CTX (a 36-amino acid peptide capable of binding preferentially to tumor cells of neuroectodermal origin but not to normal cells) along with niosomes in the chitosan hydrogel has been used as the second targeting strategy to further improve the specific delivery of drugs to tumor cells such as glioma. To investigate the possible molecular interaction between the chitosan hydrogel and various cell lines, Attenuated Total Reflectance-Fourier Transform Infra-Red (ATR-FTIR) spectroscopy has been used. The expression level of MUC1 in different cell lines was quantitatively evaluated using Cell based Enzyme Linked Immunosorbent Assay (Cell-ELISA) to better understand the mechanism involved in interactions between chitosan and specific tumor cells. In vitro release studies were performed to examine the effect of CTX on the release rates. Transmission Electron Microscopy (TEM) is being used for morphology assessments of CTX and nisomes as well as chitosan hydrogel embedded with niosomes and CTX. Cell-ELISA data revealed high expression level of MUC1 in ovarian epithelial carcinoma cell line (OV2008) and a moderate expression level in normal ovarian epithelial cell line (MCC3) implicating higher affinity of chitosan for OV2008 than MCC3 cell lines. This is consistent with ATR-FTIR results as well as the previously observed higher chitosan accumulation on the surface of OV2008 compared to MCC3, confirming the mucoadhesive property of chitosan and indicating its specificity in targeting MUC1 overexpressing tumor cells. In vitro release studies show that embedding CTX along with the niosomes does not disturb the controlled release from the chitosan network. In fact, attachment of CTX to the surface of niosomes shown by TEM imaging improves the stability of niosomes resulting in extended release rates. Based on these findings, we anticipate that the drug delivery system described here would improve tumor cell uptake of drugs due to the enhanced tumor targeting and its controlled, sustained and localized drug delivery to cancer cells. Citation Format: Rana Falahat, Eva Williams, Marzenna Wiranowska, Ryan Toomey, Norma Alcantar. Enhanced targeting delivery to tumor cells using mucoadhesive chitosan and chlorotoxin. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5410. doi:10.1158/1538-7445.AM2014-5410