Synthesis and Processing of Polydepsipeptide- and Polylactic Acid-Based Microparticles with Tunable Degradation Profiles

Polydepsipeptides (PDPs) are biocompatible polymers, whose biodegradation releases only amino acids and glycolic or lactic acids, nontoxic compounds that are naturally present in the body. These polymers therefore have great potential as materials for use in biomedical applications, particularly as drug delivery systems. Here, we investigated the organocatalyzed ring-opening polymerization (OROP) of 3-benzylmorpholine-2,5-dione (MD(Phe)) using DBU and TU as the catalytic couple to synthesize PDP(Phe) with molar masses from 2.5 to 10 kg·mol –1 . Copolymerization with lactide was also studied, with the aim of obtaining various degradation kinetics related to the enzymatic environment. PDP(Phe)- and P(MD- co -LA)-based microparticles were produced by microfluidics with diameters of 40–60 μm and narrow size distributions. Their degradation behavior was evaluated in PBS and in the presence of enzymes (esterase, α-chymotrypsin). Both PDP(Phe) and P(MD- co -LA) microparticles displayed composition- and environment-dependent degradation, releasing phenylalanine and hydrolyzed MD(Phe).