UC Irvine

Ring-Opening Polymerization-Induced Crystallization-Driven Self-Assembly (ROPI-CDSA) is a powerful method to create polymer nanoparticles for potential application in nanomedicine. In ROPI-CDSA, polyethylene glycol (PEG) is chain extended by the organocatalyzed ring-opening polymerization of L-lactide in toluene. Poly(L)-lactide (PLLA) is sparingly soluble in toluene, so the resulting PEG-b-PLLA block copolymers undergo self-assembly. For ROPI-CDSA to synthesize ideal drug delivery systems, it should utilize biocompatible components and be readily able to load drugs.Current ROPI-CDSA approaches have used organocatalysts such as 1,5,7 triazabicyclodec-5-ene (TBD) to polymerize L-lactide onto PEG. TBD would need to be purified out before use in-vivo, and while PEG is biocompatible, there have been increasing reports of allergic reactions to PEG.1 Here we show how chlorhexidine (Figure 1), an antibiotic2, can act as a replacement catalyst for TBD and be incorporated into the self-assemblies without a separate drug-loading step, and how the more biocompatible and versatile poly-2-ethoxy-2-oxo-1,3,2-dioxaphospholane (PEP) can act as a replacement for PEG.3 These studies lay the framework for new drug delivery systems. In future studies, different drugs bearing the proper functional groups can substitute for chlorhexidine. The incorporation of phosphoesters in ROPI-CDSA, such as PEP, will allow for increasing synthetic versatility as phosphoesters with different side chains can be utilized in future studies.3 Thus, the synthetic development of chlorhexidine-catalyzed ROPI-CDSA and the use of PEP in ROPI- CDSA, are the first steps towards new ROPI-CDSA drug delivery systems.