Tuning the dynamic self-assembly pathway of drug delivery vehicles can ultimately lead to control of the vehicle shape and structure. The shape and structure of the vehicle is governed by the strength and directionality of the underlying intermolecular forces between self-assembling units. When the self-assembling molecule contains a functional aromatic unit such as a drug, self-assembly in the initial stages is predominantly controlled by the stacking of these aromatic. Here we probe with free energy methods in molecular dynamics simulation the self-assembly pathway of model camptothecin-based Tubestecans that form tubular morphologies in solution. Using metadynamics with PLUMED 2 we probe the self-assembly pathway for nanotube formation using varying reaction coordinates based on the degree of stacking of the hydrophobic drug, camptothecin. We find that these methods can indeed accelerate the self-assembly pathway and give insight into how the underlying molecular structure and chemistry determines the assembly path of the vehicle.

Exploring the self-assembly pathway of drug amphiphiles

ACS Spring Meeting 2021

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