Microfluidic Controlled Self-Assembly of Polylactide (PLA)-Based Linear and Graft Copolymers into Nanoparticles with Diverse Morphologies

This study outlines the microfluidic (MF) controlled self-assembly of polylactide (PLA)-based linear and graft copolymers. The PLA-based copolymers (PLA-Cs) were synthesized through a convenient one-pot/one-step ROP/RAFT technique. Three distinct vinyl monomers─triethylene glycol methacrylate (TEGMA), 2-hydroxypropyl methacrylate (HPMA), and N-(2-hydroxypropyl) methacrylamide (HPMAA) were employed to prepare various copolymers: linear thermoresponsive polylactide-b-poly(triethylene glycol methacrylate) (PLA-b-PTEGMA), graft pseudothermoresponsive poly[N-(2-hydroxypropyl)] methacrylate-g-polylactide (PHPMA-g-PLA), and graft amphiphilic poly[N-(2-hydroxypropyl)] methacrylamide-g-polylactide (PHPMAA-g-PLA). The MF technology was utilized for the controlled self-assembly of these PLA-based BCs in a solution, resulting in a range of nanoparticle (NP) morphologies. The thermoresponsive PLA-b-PTEGMA diblock copolymer formed thermodynamically stable micelles (Ms) through kinetically controlled assemblies. Similarly, employing MF channels led to the self-assembly of PHPMA-g-PLA, yielding polymersomes (PSs) with adjustable sizes under the same solution conditions. Conversely, the PHPMAA-g-PLA copolymer generated worm-like particles (Ws). The analysis of resulting nano-objects involves techniques such as transmission electron microscopy, dynamic light scattering investigations (DLS), and small-angle X-ray scattering (SAXS). More specifically, the thermoresponsive behavior of PLA-b-PTEGMA and PHPMA-g-PLA nano-objects is validated through variable-temperature DLS, TEM, and SAXS methods. Furthermore, the study explored the specific interactions between the formed Ms, PSs, and/or Ws with proteins in human blood plasma, utilizing isothermal titration calorimetry.