Sustained Release of Hydrogen Sulfide (H2S) from Poly(Lactic Acid) Functionalized 4-Hydroxythiobenzamide Microparticles to Protect Against Oxidative Damage

Abstract

Hydrogen sulfide (H2S) has emerged as a gaseous mediator capable of exhibiting many beneficial properties including cytoprotection, anti-inflammation, and vasodilation. The study presented here provides characterization of a poly(lactic acid) polymer with a functionalized 4-hydroxythiobenzamide (PLA-4HTB) capable of extended H2S release. The polymer was used to fabricate microparticles that can be potentially loaded with a drug allowing for co-release of the drug and H2S. Microparticles with the average diameter of 500 ± 207 nm were fabricated and shown to release 77.0 ± 1.76 µM of H2S over 4 weeks (release of H2S from 1 mg of particles). To test for the antioxidant properties of the PLA-4HTB microparticles, human embryonic kidney 293 cells were first incubated with PLA-4HTB microparticles and then oxidative stress was induced using CoCl2. Particle suspensions of 1 mg/mL were shown to protect cells resulting in reactive oxygen species (ROS) levels of superoxide that were similar to that of the control group. The microparticles fabricated from the PLA-4HTB released H2S over a sustained period of weeks to months, while providing protection from ROS. The microparticles described in this article represent a new platform technology that could be used to prevent and treat diseases caused by oxidative damage.