Amphiphilic PLGA-PEG-PLGA triblock copolymer nanogels varying in gelation temperature and modulus for the extended and controlled release of hyaluronic acid

Different compositional parameters of poly(_D,L-lactic-co-glycolic acid)-b-poly(ethylene glycol) triblock copolymers (PLGA-PEG) were varied to analyze their effect on gel formation and mechanical properties. Parameters such as hydrophilic/hydrophobic ratio (PLGA/PEG ratio), lactic acid/glycolic acid ratio (LA/GA ratio), PEG molecular weight (PEG Mw), polymer solution concentration, copolymer molecular weight (Mw), and polydispersity index (PDI) were studied in this work. For copolymers with PEG Mw of 1500 Da, gelation temperature (34–37 °C) was affected by _D,L-LA/GA ratio and Mw; while modulus was affected by LA/GA ratio, Mw, and Mn. Based on the parametric study, an injectable, thermoresponsive hyaluronic acid (HA) delivery platform was designed for ocular applications. PLGA-PEG copolymers with _D,L-LA/GA ratio of 15/1, PLGA/PEG ratio of 2/1, PEG Mw of 1500 Da, and Mw of about 6 KDa gelled at 35 °C, were optically transparent, had a modulus less than 350 Pa and were used for HA release studies. This work also demonstrates, for the first time, an extended and controlled release of HA, beyond 2 weeks, from injectable hydrogels modified with a noncovalent interacting agent, poly(L-lysine). Smaller PLL chains slowed down the HA release kinetics, while larger PLL chains produced a release profile similar to the nonmodified hydrogels.