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

Abstract

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. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020, 137, 48678.

Hyaluronic Acid and Controlled Release: A Review

“…They have also claimed that an extended and controlled release of HA, beyond 2 weeks could be built from injectable hydrogels modified with a noncovalent interacting agent, poly(l-lysine) or PLL. Smaller PLL chains slowed down the HA release kinetics, while larger PLL chains produced a release profile similar to the unmodified hydrogels [50].…”

“…Osorno et al [50] produced poly(d,l-lactic-co-glycolic acid)-b-poly(ethylene glycol) triblock copolymers (PLGA-PEG) matrices to encapsulate HA and studied its controlled release. They focused on copolymer gel formation and mechanical properties on release kinetics of HA.…”

Extended Release of Doxorubicin-Loaded 3DNA Nanocarriers fromIn-SituForming, Self-Assembled Hydrogels

“…These gels can be used in combination with other natural and synthetic polymers to design more efficient matrices for the extended and controlled release of drugs. 9 Different drugs and targeting moieties can be incorporated into the system, allowing for the design of more specific and effective drug release platforms. For instance, these injectable systems can be used for a variety of ocular applications, including but not limited to, macular degeneration and secondary cataracts or posterior capsule opacification (PCO).…”

“…Moreover, we recently demonstrated that PLL can slow down the release rate and extend the release time of hyaluronic acid from these hydrophobic platforms. 9,13,14 Other localized medical conditions that can be treated by using these novel platforms are postsurgery pain, bone regeneration, spinal cord injury repair, among others.…”

“…15 These drug delivery platforms need to meet the following criteria to be injected into the lens capsule, underneath the intraocular lens, at the time of cataract surgery: gelation temperature (GT) should occur at the physiological temperature of the human lens capsule (34°C -35°C), 26 allow over 80% of light transmittance at visible wavelengths (455-700 nm) 27,28 and have a modulus of <350 Pa to prevent any damage to surrounding ocular tissue. 29,30 Based on our previous polymer characterization study, 9 the triblock copolymers that best met such criteria had the following parameters: lactic acid to glycolic acid (d,l-LA/GA) ratio of 15/1, PEG molecular weight (Mw) of 1,500 Da, PLGA/PEG ratio of 2/1, and overall Mw of 6 kDa.…”