Vandana B. Patravale

Title : Smart lipid nanocarriers: Potential for intracellular targeting

Abstract:

Intracellular delivery of anticancer drugs and therapeutic genes (DNA, siRNA, shRNA etc.) is a challenging task faced by pharmaceutical formulators necessitating the need for effective strategies which facilitate superior transfection and endosomal escaping ability. Taking this into consideration, we have designed and synthesized a novel amphiphilic, cationic heterolipid. This cationic heterolipid was employed in fabrication of smart nanocarriers namely cationic self-microemulsifying drug delivery system (C-SMEDDS) for etoposide and monoguinoplex for gene therapy. C-SMEDDS (size <50 nm and zeta potential +32.6 mV) exhibited significant in vitro antiproliferative activity against B16F10 cell line. C-SMEDDS were observed to localize in cytoplasmic, perinuclear and nuclear space of cancer cells and mechanistic studies revealed clathrin mediated pathway, cytoskeletal reorganization and energy dependent uptake as the possible cellular entry mechanisms. The in vivo antitumor activity studies in preclinical melanoma tumor model presented superior tumor suppression ability at therapeutic and sub-therapeutic dose with 100% survival without any signs of hepatotoxicity and nephrotoxicity assuring high efficacy and safety. Monoguinoplex comprised heterolipid complex with p53 gene & GFP based plasmid. The complexation resulted in condensation of DNA bulk structure that offered protection to DNA from endonuclease enzymes and the same was confirmed using DNAase protection assay. The mammalian cells transfection assay proved superior transfection with monoguinoplex and was corroborated using confocal and flow cytometry assessment. Overall, the studies revealed not only a significant enhancement in intracellular uptake but also addressed biopharmaceutical issues related to non- site specific drug delivery and associated toxicity. Thus, the developed heterolipid based nanocarriers present a smart platform for intracellular release of cargo.

Takeaway Notes:
•A thought process towards innovative formulation strategy development
•Researchers will get an outline of in-depth study planning and execution from ideation to product realization Key features: -Next generation novel and efficacious approaches to treat cancer -Industrially feasible and scalable platform technology with multitude applications

Biography:

Prof. Vandana Patravale is a Professor of Pharmaceutics at the Institute of Chemical Technology, Mumbai, India. Her research interests include the development of nano-carriers with a major emphasis on malaria, cancer, and neurodegenerative disorders; medical device development, nano-diagnostics and nano-vaccines. She has over 200 refereed publications, 2 books, 25 book chapters, 30 granted patents, and 2 trademark registries. She is the Vice President of, the CRS-Indian Chapter. She has completed Indo-Swiss, Indo-Japan, and Indo-UK projects and is a recipient of the Bill Melinda Gates Grant Award, 2015. She has transferred many technologies to industries including drug-eluting stents, which are being marketed in about 65 countries.