Structure of PLGA and Its Cardio-Protective Effect: Atomic Simulation and Machine Learning

Poly lactic-co-glycolic acid (PLGA) is a polymer consists of lactic acids and glycolic acids subunits. Being relatively inert, and able to break down in human body with no significant toxic effect to human body, PLGA has been FDA-approved and used in a wide range of medicine. However, the relation between its physio-chemical properties and biological properties remains unclear. In the case of doxorubicin, a drug that is commonly used in chemotherapy, while being very effective in fighting cancer, doxorubicin is also cardiotoxic leading to a tremendous risk of heart disease in cancer patients. We demonstrate here that PLGA in conjunction with doxorubicin mitigated cardiotoxicity effects in cultured cardiac cells increasing survival. To investigate the mechanism of PLGA’s cardio-protective effects we applied machine learning techniques including k-means clustering and random forest classification to unbiasedly identify the most important factors for PLGA’s enhancement on cell viability. Furthermore, we performed Quantum Expresso simulations to model the PLGA bond length, coordination numbers, density, etc. We analyzed the electronic and energetic distributions of PLGA to better understand the structure and function and to further optimize PLGA’s therapeutic potentials.