Synthesis and Characterization of Inhibitor Loaded Nanoparticles for Temporal Targeting of PI3K Signalling

Abstract

The phosphatidylinositol 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) signaling pathways play a pivotal role in the growth and survival of various cancers. PI103, a small molecule inhibitor targeting PI3K/AKT/mTOR pathway is a promising anti- cancer agent. Major drawback of this drug is its poor water solubility and off-target toxicity. These limitations can be overcome by harnessing nanotechnology based approaches. Traditional nano-formulations are not always compatible with the physicochemical properties of the agents, leading to poor encapsulation efficiency, sub-optimal uncontrolled drug release, reduced efficacy and vector related toxicity. To address these challenges, we have developed two novel nano-platforms, based on rational design of molecules that facilitate supramolecular self-assembly. In current study we have developed a novel vitamin D3 (cholecaciferol) and lithocholic acid nanoparticles for delivery of PI3K signalling inhibitor in cancer. These nanocarriers are characterized for size, shape and morphology using dynamic light scattering (DLS) and electronic microscopic techniques. Sustained release of bioactive drug over the period of five days is investigated. This study demonstrates the potential of vitamin D3 and lithocholic acid as promising novel nanovectors for delivery of the PI3K signaling inhibitor in cancer.