Cataracts, one of the leading causes of preventable blindness worldwide, refers to lens degradation that is characterized by clouding, with consequent blurry vision. As life expectancies improve, the number of people affected with cataracts is predicted to increase worldwide, especially in low-income nations with limited access to surgery. Although cataract surgery is considered safe, it is associated with some complications such as retinal detachment, warranting a search for cheap, pharmacological alternatives to the management of this ocular disease. The lens is richly endowed with a complex system of non-enzymatic and enzymatic antioxidants which scavenge reactive oxygen species to preserve lens proteins. Depletion and/or failure in this primary antioxidant defense system contributes to the damage observed in lenticular molecules and their repair mechanisms, ultimately causing cataracts. Several attempts have been made to counteract experimentally induced cataract using in vitro, ex vivo, and in vivo techniques. The majority of the anti-cataract compounds tested, including plant extracts and naturally-occurring compounds, lies in their antioxidant and/or free radical scavenging and/or anti-inflammatory propensity. In addition to providing an overview of the pathophysiology of cataracts, this review focuses on the role of various categories of natural and synthetic compounds on experimentally-induced cataracts.
Purpose
Although 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.
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
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