Nanoprecipitation and Drug Delivery with PMTC: Toward Biomedical Application of Polyesters from Radical Ring-Opening...

Polymerized cyclic ketene acetals (PCKAs) prepared by radical ring-opening polymerization (RROP) have shown tremendous potential in the biomedical field. In this work, the field is expanded to the formation of fully degradable nanoparticles (NPs) from the fast-degrading poly(2-methylene-1,3,6-trioxocane) (PMTC). The formulation of homopolymers is typically challenging due to their lack of amphiphilicity; however, implementing nanoprecipitation as a robust, fast, and cost-efficient method of self-assembly has yielded well-defined polymeric nanocarriers of 100-200 nm in diameter. The characterization of hydrophilicity and dye-encapsulation mediated via different polyester degrees of branching has enabled insights into utilizing this key characteristic of RROP. The degree of branching affected dye encapsulation in the absence of altering hydrophilicity. The highest levels of encapsulated Coumarine-6 (Cou6) as a model drug were found with polymers possessing an intermediate degree of branching (8%) at low molecular weight (9 kg/mol). In addition to stable NPs, the disassembly of these NPs in extreme pH regions promised potential for targeted drug delivery. In vitro studies have demonstrated the cytocompatibility of NPs and their degradation products, and their ability to achieve cell uptake of Cou6-loaded NPs has been confirmed, highlighting the potential of PMTC-NPs as drug delivery vehicles. The successful protocol to prepare NPs purely of polymerized CKAs demonstrated here thus enables future efforts to expand the library of NPs from RROP.