Biocompatible amphiphilic pentablock copolymeric nanoparticles for anti-cancer drug delivery.

A pentablock copolymer of Poly(Lactide-co-Glycolide) and Pluronic F68 was synthesized using ring-opening polymerization and characterized by NMR and FTIR for confirming the structure of the block copolymer. TG-DTA studies showed PLGA:Pluronic ratio to be 4:1. As the PLGA-PEO-PPO-PEO-PLGA Pentablock Copolymer (PPPC) prepared is amphiphilic, its Critical Vesicular Concentration, was measured, which was lower at 37 degrees C than at 25 degrees C, which could provide better stability to the system at physiological temperature. The nanoparticles of PPPC vary in topographyand range from 150 to 500 nm in size, according to the synthesis route used viz Emulsion Solvent Evaporation and simple dialysis. Pentablock copolymer nanoparticles were found to entrap about 84% of hydrophobic drug, docetaxel. Drug release profile of docetaxel showed about 50% release in first 2 hours at pH 4.6 and about 80% docetaxel was released at pH 7.4, at the end of 2 days. The PPPC nanoparticles was found to be biocompatible to L929 cell lines up to 1 mg/ml concentration. Preliminary in vitro cytotoxic effect of docetaxel loaded PPPC nanoparticles against four different cancer cell lines showed 50% inhibitory concentration of 6 nM in A431 (Squamous cell carcinoma), 250 nM in HeLa (Cervical carcinoma), 800 nM in PC3 (Prostate carcinoma) and 1 microM in KB (Epidermoid carcinoma) cells.

Andrographolide inhibits osteopontin expression and breast tumor growth through down regulation of PI3 kinase/Akt signaling pathway.

Breast cancer is one of the most common cancers among women in India and around the world. Despite recent advancement in the treatment of breast cancer, the results of chemotherapy to date remain unsatisfactory, prompting a need to identify natural agents that could target cancer efficiently with least side effects. Andrographolide (Andro) is one such molecule which has been shown to possess inhibitory effect on cancer cell growth. In this study, Andro, a natural diterpenoid lactone isolated from Andrographis paniculata has been shown to inhibit breast cancer cell proliferation, migration and arrest cell cycle at G2/M phase and induces apoptosis through caspase independent pathway. Our experimental evidences suggest that Andro attenuates endothelial cell motility and tumor-endothelial cell interaction. Moreover, Andro suppresses breast tumor growth in orthotopic NOD/SCID mice model. The anti-tumor activity of Andro in both in vitro and in vivo model was correlated with down regulation of PI3 kinase/Akt activation and inhibition of pro-angiogenic molecules such as OPN and VEGF expressions. Collectively, these results demonstrate that Andro may act as an effective anti-tumor and anti-angiogenic agent for the treatment of breast cancer.