Developing an efficient ocular delivery system for the hydrogen sulfide releasing compound, diallyl trisulfide

Purpose Although hydrogen sulfide (H 2 S) exhibits ocular hypotensive and retinal neuroprotective actions ( Ohia et al., JOPT, 34:61,2018), its ocular delivery is challenging. Diallyl trisulfide (DATS) is a lipophilic, H 2 S‐releasing compound that rapidly degrades under aqueous conditions. Therefore, we sought to prepare a novel solid lipid nanoparticle (SLN) of DATS for ocular delivery. Methods DATS content was determined by HPLC method using standard solutions (3.12–100 ug/ml). The HPLC parameters consisted of C18 column (Zorbax, 150 mm × 4.6 mm, 5 μm) isocratic elution with methanol and water (85:15). Following method validation, the SLN loaded with DATS were prepared using hot emulsification process, characterized and influence of process parameters on particle size were evaluated. Results A well resolved DATS peak was detected at 2.8 mins. The method was validated for linearity (R2 > 0.999); precision (<10%) and accuracy (>90 %). Increasing the concentration of the poloxamer 188 from 0.2% to 1% (w/v) decreased the particle size from 296.7 to 90.46nm. Increasing lipid concentration from 1% to 3% (w/v) increased particle size from 65±5 to 103.4 ± 6 nm. Without the surfactant, glyceryl behenate (GBH) elicited higher particle size (330.8 ± 8.5 nm) than glyceryl monostearate (GMS) (254.4 ± 5.5 nm). Presence of surfactant (poloxamer 1%, soy lecithin 0.2%) reduced particle size to 238.6 ± 8 nm and 85 ± 4.5 nm for GBH and GMS, respectively. Thus, GBH was selected for SLNs and particle size, polydispersity index, zeta potential, and drug loading were 124 ± 2.67 nm, 0.189 ± 0.005, −23.57 ± 3.22mV and 1.5%, respectively. FTIR studies indicated complete encapsulation of DATS. Conclusion An accurate method for quantification of DATS was developed and validated. A biocompatible system for delivery of DATS was obtained with a particle size less than 200 nm. Studies are in progress to determine release pattern in ocular tissues. Support or Funding Information Creighton University‐SPAHP, Pharmaceutical Sciences Graduate Program