Abstract 2897: Preferential drug delivery to cancer cells than to normal cells by using the Niosome-Chitosan Thermo-responsive Double Package System (NCTR-DPS)
Authors: Eva Christabel Williams, Marzenna Wiranowska, Marcia Gordon, Ryan Toomey, Gael Nicolas, Norma Alcantar
Journal: Cancer Research (2012)

Abstract The main challenge of this research is to develop a localized, cost effective drug delivery system that can provide control over the release of drugs in ovarian cancer or brain tumor patients, in a manner that also reduces chemotherapeutic toxicity. We have designed a drug delivery system consisting of non-ionic surfactant vesicles (niosomes) packaged within a biodegradable, temperature sensitive hydrogel (chitosan) network (NCTR-DPS). Two chemotherapeutics, Paclitaxel and Carboplatin, conjugated to BODIPY 564/570 (RED fluorescence dye) were encapsulated in the NCTR-DPS. Their release was evaluated either in cell free system or following incubation with human cell lines: glioma (U373), ovarian carcinoma (OV2008), and two normal ovarian epithelial (MCC3 and I-Low) cell lines. Cellular localization of Paclitaxel-RED in live cells was evaluated using confocal microscopy and the level of direct fluorescence quantified with LAS AF software. Confocal imaging of the cells verified that the activity of the drugs remained intact within the drug delivery system. The cellular drug delivery was confirmed by cell's toxicity observed within two hours of incubation. The control study showed no toxicity of the niosome-chitosan alone (without the chemotherapeutics). Chitosan accumulation was greater on OV2008 cell surface than on MCC3 or I-Low cells. Also, significantly higher Paclitaxel-RED fluorescence was found in OV2008 compared to normal MCC3 cells, indicating a specific interaction between chitosan and Mucin1 (MUC1) receptors over expressed in ovarian carcinoma. These data were further confirmed by ATR-FTIR (Attenuated Total Reflectance- Fourier Transform Infra-Red) spectroscopy showing higher MUC1 levels in OV2008 than in normal epithelial cells. In addition, in-vivo examinations of the NCTR-DPS were carried out in 8-week old female mice (Strain: FVB/NJ) using Xenogen IVIS Spectrum to quantitatively monitor release of tracer molecules.In-vivo examinations revealed the release dependence on the packaging density; 25 - 40% of release occurred within 24 hours, followed by a steady release for over 14 days. By the 14th day, 98% of dye was released. Higher percentage release was observed for greater niosome chitosan ratios. Our results showed that the time release of the drugs could be finely controlled by varying packaging and 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). This NCTS-DPS drug delivery system can be injected directly to tumor sites preventing the need for surgical implantation. It may have positive implications in the treatment of ovarian cancer preferentially targeting tumor cells or brain tumors because of its controlled and localized release. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2897. doi:1538-7445.AM2012-2897