DEVELOPING A NOVEL LIPID-BASED SYSTEM OF DIALLYL TRISULFIDE (DATS) FOR SUSTAINED DELIVERY OF HYDROGEN SULFIDE FOR THE TREATMENT OF GLAUCOMA

Abstract

Purpose : Glaucoma, an ocular neuropathy, is characterized by progressive degeneration of retinal neurons. Current glaucoma therapies provide only symptomatic management by reducing IOP. Since glaucoma is reported even in normotensive patients, the ideal glaucoma medication should simultaneously lower IOP and confer neuroprotection to retinal neurons. Hydrogen sulfide (H₂S) has been reported to reduce IOP and elicit retinal neuroprotection in mammalian ocular tissues. Due to gaseous nature of H₂S and narrow therapeutic index, its delivery in ocular tissues involves unique challenges. Diallyl Trisulfide (DATS) is a lipophilic, potent, and fast H₂S donor reported to degrade rapidly under normal aqueous conditions. The objective of this study is to develop a novel lipid-based delivery system of DATS to provide sustain release of H₂S up to 8-9 hours upon topical application on cornea.

Methods : DATS content was determined by HPLC method in the concentration range of 3.12 – 100 µg/ml. The method was validated for specificity, linearity, accuracy and precision. The solid lipid nanoparticles (SLNs) loaded with DATS were prepared by using hot emulsification process and solvent evaporation method. DATS-SLNs characterized for particle size, zeta potential, drug loading and encapsulation efficiency. The in vitro release studies for both DATS and H₂S were performed by incorporating DATS-SLNs in PEG ointment base.

Results : A well resolved peak of DATS was detected at 2.8 mins run time. The method showed good linearity (R2 > 0.999) over the concentration range of 3.12-100 ug/ml. Particle size was higly dependant on the concetration of polymer, lipid and surfactant. In presence of surfactant (poloxamer 1%, soy lecithin 0.2%), the particle size was 238.6 ± 8 nm and 85 ± 4.5 nm for glyceryl behenate and glyceryl monostearate, respectively showing a corresponding decrease of 28 ± 0.56% and 66 ± 1.8%. PEG ointment base incorporated with DATS-SLNs showed a sustained release of DATS up to 9 hours releasing 67.89 ± 2.04% of the initial loaded amount with corresponding hydrogen sulfide concentration of 112 ± 2.16 µM.

Conclusions : A precise and accurate method for quantification of DATS was developed and validated in compliance of USP guidelines. A biocompatible system capable of sustaining H₂S release from DATS was obtained with a particle size less than 200 nm up to 9 hrs.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.