Drug catalyzed polymerization yields one pot nanomedicines†

Ring-opening polymerization (ROP) is a powerful method for the synthesis of biocompatible and biodegradable polyester-based amphiphilic block copolymers, which are an excellent nanomaterial class for a wide range of pharmaceutical applications. These block copolymers are synthesized using a catalyst, which is typically purified out. In a separate step, the purified block copolymers are then assembled and drug-loaded for medical use. This multistep process limits the scalability of these nanomaterials restraining their industrial use. Recently, we developed a synchronous polymerization and self-assembly process for polyester-based block copolymer nanomaterials coined Ring-Opening Polymerization-Induced Crystallization-Driven Self Assembly (ROPI-CDSA). In ROPI-CDSA, an organocatalyst facilitates the chain extension of mPEG with L-lactide, yielding semicrystalline self-assemblies. Here, we demonstrate that pharmaceuticals with similar functional groups to ROP organocatalysts can catalyze ROPI-CDSA reactions, resulting in the formation of drug-embedded nanomaterials. The major advantage of this one pot approach is that no additional synthetic steps or purification are required. As a proof-of-principle study, we use two antibiotic drug molecules, chlorhexidine, and trimethoprim, as catalysts. Chlorhexidine acts as a co-initiator and a catalyst leading to drug conjugation whereas trimethoprim acts solely as a catalyst leading to drug encapsulation. The resulting drug-embedded block copolymer nanoparticles retain potent antibacterial activity. We anticipate that this strategy can be extended to other examples of PISA for the scalable production of drug-loaded polymer suspensions.