Amphiphilic Polymeric Architectures Based on PolyLactic Acid: Synthesis and Biological Applications

Amphiphilic copolymers, characterized by both hydrophilic and hydrophobic segments of tunable length, represent versatile drug delivery platforms due to the ability to self-assemble into micelles, vesicles, and other nanostructures. During self-assembly, they can incorporate drugs enhancing solubility and stability, enabling controlled and targeted release. Overall, amphiphilic polymers play a crucial role in nanomedicine, nanotechnology, and surface engineering owing to highly controllable chemical composition and properties.1 Amphiphilic copolymers based on PolyLactic Acid (PLA) are widely investigated for drug delivery owing to favorable drug release and tunable chemical structure which enables functional modifications and active targeting strategies. Their synthesis requires precise control over molecular weight, chemical composition, hydrophobic-to-hydrophilic balance, and accessibility of end-chain functionalities, as these parameters significantly affect polymer properties (e.g. crystallinity, degradation rate, micellization). In this presentation, the design and synthesis of various amphiphilic PLA-based architectures (i.e., linear, cyclic and branched) will be discussed. Leveraging controlled polymerization strategies and coupling chemistry, a high degree of structural precision was achieved.2,3,4 Both covalent and supramolecular approaches were employed for the design of PLA nanostructures allowing for intriguing biological applications. The main design criteria used to synthetize the materials, physicochemical properties, intracellular trafficking and biological profile were investigated. Drawing upon recent outcomes of our scientific runway, promises and limits of amphiphilic PLA-based antimicrobial and antitumoral nanotherapeutics will be discussed.