Developing an Efficient Ocular Delivery System for the Hydrogen Sulfide Releasing Compound, Diallyl Trisulfide

PurposeAlthough hydrogen sulfide (H2S) 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, H2S‐releasing compound that rapidly degrades under aqueous conditions. Therefore, we sought to prepare a novel solid lipid nanoparticle (SLN) of DATS for ocular delivery.MethodsDATS 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.ResultsA 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.ConclusionAn 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 InformationCreighton University‐SPAHP, Pharmaceutical Sciences Graduate Program