(404e) Multiscale Modeling Approach to Determine the Role of Amphiphilic Building Block in the Stability of Paclitaxel Drug Delivery Nanocarriers

Polymeric micelles are a promising class of drug delivery carriers in field of cancer therapy due to their tunable physiochemical properties. Typically, drug delivery nanocarriers are prepared from self-assembled amphiphilic block copolymers that have a biocompatible hydrophilic shell and a hydrophobic core capable of encapsulating cancer drugs such as paclitaxel (PTX). Designing optimal nanocarriers, however, is challenging due to stringent design requirements such as stability, drug-loading capacity, size distribution, and target specificity. Here we adopted a multiscale computational approach in conjunction with experiments to evaluate the building blocks of highly tunable linear polyethylene glycol-b-dendritic oligo(cholic acid) copolymer called telodendrimer. The multiscale approach involved molecular dynamics simulations of the telodendrimers and paclitaxel in coarse grained simulations for over 0.1 µs to capture micelle formation and drug encapsulation followed by reverse mapping to atomistic representation for structural analysis. Among the possible telodendrimeric structures studied, the simulations showed that PEG^5kCA₈ telodendrimerforms stable monodisperse micelles with 27.7±5.5 nm diameter and highest drug loading capacity of 25% w/w, which is in excellent agreement with the experimental results (21.4±4.0 nm). This multiscale approach allows us to overcome the computational bottleneck of simulating large systems without sacrificing the relevant chemical interactions in the nanocarrier-drug micelle.