A novel particle-based in situ gelling system for delivering hydrogen sulfide at a sustained rate for potential application in glaucoma and retinal neurodegeneration
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Authors
Verma, Richa
Issue Date
2017-07-05
Volume
Issue
Type
Thesis
Language
en_US
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Abstract
H2S is reported to have tremendous therapeutic potential indicated by its roles in anti-inflammation, anti-tumor, ion channel regulation, cardiovascular protection, and anti-oxidation effects. One of the most important therapeutic potential lies in the treatment and management of glaucoma, a condition which is characterized by elevated intraocular pressure (IOP) and neurodegeneration of retina ganglion cell and optic nerve head. If left untreated it may cause blindness. Current therapies help in lowering the IOP, however, it is the neurodegeneration which plays a key role in blindness. Hydrogen sulfide functions both as a neuroprotectant and IOP lowering agent at 10-200 μM concentration. But due to its narrow therapeutic window (less than 200 μM) profile, it must be delivered at a therapeutically relevant low sustained rate. However, the delivery of H2S is associated with multiple challenges, including a narrow potential therapeutic window, aqueous instability of H2S donors, gaseous nature at standard temperature and pressure, and a high burst release from its delivery system that could potentially induce immediate and intense pro-inflammatory response and toxicity. Therefore, this study investigated as a proof-of-concept the efficiency of a novel particulate-based in situ gelling system for delivering H2S at a sustained rate for longer period of time. Polycaprolactone-based microparticles loaded with a model H2S donors were prepared and characterized for size and surface charge. The size of the particles obtained was (141.26 ± 5.59 and the charge was equal to -82.08 mV implying easy passage through a 25-gauge needle and uniform dispersion in the formulation, respectively. Particles were dispersed in PLGA solution (15% w/v in triacetin) which was injected in modified STF resulting in instantaneous formation of a gel in situ. STF samples were withdrawn at specific time points to analyze for H2S content. The particulate gelling system significantly (p<0.05) sustained the H2S release up to 144 hours in comparison to non-particulate system. Rheological studies indicated its easy injectability and syringeability. No significant (p<0.05) change in pH of STF was determined after injecting the formulation. Cellular viability study conducted using Y-79 retinoblastoma cells indicated significantly (p<0.05) greater viability with all formulation components in comparison to the positive control.
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Citation
Publisher
Creighton University
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Copyright is retained by the Author. A non-exclusive distribution right is granted to Creighton University and to ProQuest following the publishing model selected above.