Abstract
Purpose :
To evaluate the pharmacological and safety profile of two new betamethasone/chloramphenicol gel formulations with or w/o preservative, versus other steroid/antibiotic combinations.
Methods :
Corneal epithelial cells were used. After cell exposure to ocular formulations, cell viability, along with occludin levels, were assessed by ATPlite and WB, respectively. Wound healing was carried out by scratch assay. Cells were exposed to: ZiclorP gel [0.1% betamethasone (BET)/0.25% chloramphenicol (CHL) with parabens; Alfa Intes], Betabioptal gel (0.1% BET/0.25% CHL with thiomersal; Thea), Netildex eye-drops [0.1% dexamethasone (DEX)/0.3% netilmicin with benzalkonium chloride (BAK); SIFI] and Ducressa eye-drops (0.1% DEX/0.5% levofloxacin; with BAK; Santen). Albino rabbits were used for ocular pharmacokinetic (PK) study (ARVO Statement for Use of Animals in Ophthalmic Vision Research). Two groups of rabbits were treated with a single topical administration (30µl) of 0.1% BET gel formulation w/o parabens (ZiclorPF) and 0.1% DEX eye-drops (Ducressa), respectively. Aqueous was collected at 30, 60, 120, 180, and 240 mins after treatment, and levels of steroid detected by LC-MS/MS.
Results :
ATP levels were significantly (p<0.05) reduced by the three formulations exposure compared to the new gel ZiclorP. A significant (p<0.05) wound closure area was observed after the exposure with ZiclorP compared with the other products. Occludin expression was maintained at physiological levels in the cells exposed to ZiclorP; on the contrary the other formulations elicited a significant (p<0.05) protein’s reduction. PK study showed no significant difference in terms of AUC and Cmax between ZiclorPF and Ducressa (AUC0-240 1943 and 1827 ng/ml*min, Cmax 11.75 and 11.42 ng/ml for gel and eye drops formulations, respectively). However, after 180- and 240-min BET levels were significantly (p<0.05) higher compared to DEX.
Conclusions :
The new ophthalmic gel formulations have a good pharmacological and safety profile. PK study showed higher levels of steroid in anterior chamber with ZiclorPF, suggesting a longer pre-corneal residence time compared to Ducressa eye drops. Cells treated with ZiclorP showed a better viability and wound healing compared to the other formulations, preserving cell barrier connections, and suggesting that ZiclorP has a minimum impact on cell repair process.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.