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

Area of Science:

• Polymer Chemistry
• Biomaterials Science
• Drug Delivery Systems

Background:

• Polydepsipeptides (PDPs) are biocompatible polymers that degrade into non-toxic, naturally occurring substances like amino acids and lactic/glycolic acids.
• Their biocompatibility and tunable degradation make them highly suitable for biomedical applications, especially in drug delivery systems.
• Controlled synthesis of specific PDP structures is crucial for tailoring their performance in vivo.

Purpose of the Study:

• To synthesize polydepsipeptides (PDP(Phe)) and their copolymers with lactide (P(MD-co-LA)) using organocatalyzed ring-opening polymerization (OROP).
• To fabricate microparticles from these polymers using microfluidics for potential drug delivery applications.
• To investigate the degradation behavior of these microparticles in different environments, including enzymatic conditions.

Main Methods:

• Organocatalyzed ring-opening polymerization (OROP) of 3-benzylmorpholine-2,5-dione (MD(Phe)) using DBU/TU catalyst couple.
• Copolymerization of MD(Phe) with lactide to create tunable degradation profiles.
• Microfluidic production of microparticles with controlled size (40-60 μm) and narrow size distribution.
• In vitro degradation studies in phosphate-buffered saline (PBS) and enzymatic solutions (esterase, α-chymotrypsin).

Main Results:

• PDP(Phe) synthesized with controlled molar masses (2.5-10 kg·mol⁻¹).
• Successfully produced uniform PDP(Phe)- and P(MD-co-LA)-based microparticles via microfluidics.
• Demonstrated composition- and environment-dependent degradation of microparticles.
• Identified release of phenylalanine and hydrolyzed MD(Phe) during degradation, confirming breakdown into natural components.

Conclusions:

• Organocatalyzed polymerization enables synthesis of biocompatible PDPs and copolymers for biomedical use.
• Microfluidics allows for precise fabrication of drug-delivery-sized microparticles from these polymers.
• The tunable degradation kinetics in response to biological environments highlight the potential of these PDP-based materials for advanced drug delivery systems.