Cross-disciplinary Optimization of Nano-Drug Delivery to Ovarian Carcinoma and Glioma Cells
Poster Feb 13, 2017
Rupin Singh, Rana Falahat, Eva Williams, Joseph O. Johnson, Norma Alcantar, Aleksandra Karolak, Katarzyna Rejniak, Marzenna Wiranowska
This study reports on the quantitative analysis of the diffusion and localization of a targeted drug delivery system (DDS) consisting of fluorescent labeled 0.01 µM paclitaxel-BODIPY 564/570 encapsulated in non-ionic surfactant vesicles embedded in a thermosensitive cross-linked chitosan hydrogel. This is a multi-tiered DDS that allows for enhanced stability, sustained and controlled delivery of embedded drugs to tumor sites, and reduced toxicity. We showed that cancer cells of epithelial origin, such as human ovarian epithelial carcinoma OV2008 and highly migratory mouse glioma G-26, overexpress MUC1, a mucin surface antigen, which effectively enhances the specific targeting capacity of chitosan. Utilizing this DDS we found that OV2008 carcinoma cells had ~2 times higher fluorescence intensity level than normal ovarian epithelial IMCC3 cells with a statistical significance at 5 min and 24 h incubation times suggesting that this DDS had a higher affinity for tumor cells. Therefore, we hypothesized that there is a difference in PTX diffusion towards epithelial origin tumor cells when compared to normal cells in both distance/location and time. Diffusion and localization of fluorescent labeled PTX was evaluated in vitro using confocal microscopy. The fluorescence intensity captured on the images was quantified with ImageJ software in OV2008 carcinoma cells and compared to IMCC3 normal cells at time intervals 5 min, 1 h, 24 h, 48 h, and 72 h. The fluorescence intensity image data was analyzed in multiple radial line segments separated into three different zones of 24 µm each to represent multiple diffusion distances. Our results showed that fluorescence intensity levels in the zones around the IMCC3 normal cells at 5 min and 1 h were significantly higher (p<0.05) than around OV2008 carcinoma cells correlating reciprocally with our finding of intracellular fluorescence intensity in these two cell lines. Therefore, the data evaluating fluorescence levels in the radial zones outside the cells indicated that the migrating DDS-PTX had already been taken up by the tumor cells. Furthermore, the normal cells which showed significantly lower intracellular levels of fluorescence had higher levels of fluorescence in the measured radial zones outside the cells.
This PTX-BODIPY 564/570 diffusion data from in vitro studies is currently being used for computational modeling in the in vivo intracerebral model of G-26 glioma. It will be integrated with mathematical model simulations that describe the pharmacokinetic and pharmacodynamic (PK/PD) properties of this drug delivery system for the evaluation of its efficacy and to optimize drug delivery in vivo. Computational modelling is being done in Matlab using the treatment scenario of the post-surgical late-stage glioma. The simulation studies will be used to determine optimal drug concentrations, chitosan density, and localization.
Electrophysiological Changes Underlying Lapses in Memory ConsolidationPoster
In this study we explore the electrophysiological changes associated with lapses in memory consolidation.READ MORE
A Real-Time Annexin V Method for Monitoring Programmed Cell DeathPoster
The RealTime-Glo™ Annexin V Apoptosis and Necrosis Assay detects the kinetics of apoptosis and secondary necrosis in real time resulting from a variety of treatments (including biologics) to induce cell deathREAD MORE
Preclinical drug screening in new generation Alzheimer’s disease mouse models: The MODEL-AD Consortium StrategyPoster
A brief overview of the Preclinical Testing Core of the MODEL-AD consortium.READ MORE