This research studies co-polymeric nanoparticles (NPs) with desirable properties like biocompatibility and drug loading ability for their responsiveness to pH driven stimuli. Preliminary experiments have confirmed that the covalent conjugation of co-polymer polycarbonate 2 pyrrolidine-1-yl-ethyl-amine (PCPY) to Doxorubicin (DOX) molecule attenuates cardiotoxicity in the cardiomyocytes. Assumptively, the choice of tertiary amines, surface charge and their loading technique of DOX influence behavior of co-polymeric PCPY NPs. Hence, it is important to investigate their molecular interactions, encapsulation and release mechanisms of DOX. The goal of this study is to understand these underlying molecular mechanisms of co-polymeric PCPY-NPs and their interactions, specifically, in terms of their release and encapsulation of DOX. By employing all-atomistic molecular dynamics (AA-MD), this process can unveil the molecular and atomistic properties of PCPY NPs and PCPY-cDOX complex. Analytical parameters, i.e. radius of gyration, hydrogen bonding analysis, root mean square displacement and radial distribution function will explain these mechanisms. We have employed NAMD software in modeling PCPY and PCPY-cDOX complex in varying pH levels. We employ in these simulations the CHARMM force field. The simulations are conducted in water medium and Constant-pH MD methodology is applied to vary the pH levels respectively. The results observed support the encapsulation of DOX in a pH of 7.4 and the release of DOX at pH of 5.0 respectively. Assumptively, other factors like length of hydrophobic & hydrophilic segments and hydrophobic-lipophilic balance (HLB) could be influencing the formation and deformation of PCPY NPs and PCPY-cDOX complex. Hence, this study will be a bedrock for elucidating these mechanisms and characteristics for further experimental advancements.

Computational study of block copolymer encapsulation that attenuates cardiotoxicity and maintains the efficacy of anticancer doxorubicin molecule

ACS Fall 2021

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