Morteza Rasoulianboroujeni, Pharmaceutical Sciences graduate student (Kwon Research Group), will be defending his PhD research thesis:

New Insights into the Fabrication of Drug-Loaded Polymeric Micelles

This study aimed to develop a safe and scalable method for fabricating drug-loaded polymeric micelles while addressing the challenges of long-term storage. Current fabrication methods present serious challenges in the development procedure, including the utilization of toxic solvents, the requirement for specialized equipment, and difficulties in solid form production. We hypothesized that by utilizing low molecular weight PEGs, known for their ability to dissolve hydrophobic drugs at elevated temperatures, as an alternative solvent, these challenges could be overcome in the production of drug-loaded micelles.

We first focused on investigating micelle formation in a copolymer/PEG/water mixture using a model based on mean-field lattice theory. The model considered the free energy and translational entropy of the micelles, revealing the existence of entropy-driven liquid-liquid phase separation (LLPS) preceding micelle formation. This event can be controlled by varying the degree of polymerization. Experimental validation confirmed the accuracy of the model using PEG4kDa-b-PLA2.2kDa as the copolymer and PEG as the solvent.

Building on this system, we introduced the “PEG-assist” method for fabricating drug-loaded polymeric micelles by hydrating a mixture of PEG, copolymer, and drug. The properties of the resulting micelles were influenced by the molecular weight of PEG and temperature, both are known to impact LLPS and solvation power of PEG. The method’s adaptability to other drugs and copolymers, scalability, freeze-drying feasibility, and stability were also proved. Furthermore, we proposed a formulation strategy for producing drug-loaded polymeric micelles directly from a solid form.

In summary, this study presents a comprehensive approach for fabricating drug-loaded polymeric micelles from a physical chemistry perspective, providing alternatives to current fabrication methods.