Abstract 5534: Novel pluronic F127-coated paclitaxel nanoparticles formulation for pancreatic cancer
Authors: Yallapu Murali M. , Chauhan Neeraj , Khan Sheema , Jaggi Meena , Ganju Aditya , Maher Diane M. , Ebeling Mara C. , Chauhan Subhash C. 
Published: August 2015

Abstract
Pancreatic cancer (PanCa) is one of the deadliest cancers which accounts for 46,420 new cancer cases and almost 39,590 deaths in the United States in 2014. There is no effective treatment modality for PanCa that can significantly improve the overall survival rate of patients. Paclitaxel is a mitotic inhibitor widely used in chemotherapy. Recent FDA approved treatment regimen of Abraxane® (paclitaxel nanoformulation) with gemcitabine has been increased overall survival of PanCa patients from 6.7 months (Gemcitabine) to 8.5 months (Abraxane® + Gemcitabine). Targeted delivery of paclitaxel may lead to significant improvement in treating pancreatic cancer. For this purpose, we have engineered a unique, pluronic F127-coated paclitaxel loaded nanoparticles (PPNPs) formulation. This formulation is composed of a PLGA core that is subsequently coated with poly(vinyl alcohol) (PVA), poly(l-lysine) (PLL), and pluronic polymer (F127) for efficient drug delivery and active tumors targeting. This formulation has several unique properties: (a) the PLGA core is capable of loading paclitaxel and its sustained release (b) pluronic-polymer layer coating provides stability and also reverses multi-drug resistance in cancer cells (c) the polyethylene glycol chains of pluronic F127 polymer act as a stealth polymer which diminishes the nonspecific uptake of formulation, and (d) amine functional groups on NPs (PLL) are useful for antibody conjugation through a PEG-linker for specific targeting of tumor/cancer cells. The PPNPs formulation was characterized for particle size, chemical composition, and thermal characteristics. The PPNPs exhibited superior dose-dependent inhibition effects on the proliferation of Colo-357, HPAF-II, BxPC-3, MiaPaca-2, Panca-1, and AsPC-1 pancreatic cancer cell lines, over free PTX and other conventional PTX nanoformulation (Abraxane®). Similar inhibition effects were also observed in colony formation assay in BxPC-3 cells. The improved anti-cancer effects of this formulation was achieved due to its accumulation in the cytosolic compartment and less presence in early endosome/late endosome/lysosome indicates their escape from lysosomal degradation. In addition, our data suggest that F127-stabilized PPNPs exhibit superior anti-cancer potential and is capable of regulating proteins associated with sonic hedgehog, multi drug resistance and miR-21 signaling pathways and inducing apoptosis which, eventually lead to the gemcitabine chemo-sensitization. Interestingly, MUC13-conjugated nanoformulation exhibited efficient targeting in HPAF-II cells. In conclusion, our data suggest that the PPNPs nanoformulation can be used for the efficient, targeted delivery of paclitaxel to tumors and may useful for treatment of pancreatic cancer alone and/or in combination with gemcitabine.
Citation Format: Murali M. Yallapu, Neeraj Chauhan, Sheema Khan, Meena Jaggi, Aditya Ganju, Diane M. Maher, Mara C. Ebeling, Subhash C. Chauhan. Novel pluronic F127-coated paclitaxel nanoparticles formulation for pancreatic cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5534. doi:10.1158/1538-7445.AM2015-5534