Determining the effect of ocular chemical injuries on topical drug delivery

Abstract

Ocular chemical injuries (OCIs) commonly cause ocular damage and visual loss and treatment uses topical therapies to facilitate healing and limit complications. However, the impact of chemical injury on corneal barrier function and treatment penetration is unknown. Therefore, the aim of this study was to determine the effect of OCI on drug penetration and absorption. Porcine corneal explants were used to assess histological damage, electrical resistance, and the trans-corneal penetration/corneal adsorption of reference compounds (sodium fluorescein and rhodamine B) and dexamethasone. Corneal explants were injured with either 1 M sulfuric acid, or 1 M sodium hydroxide. Dexamethasone penetration was measured using high-performance liquid chromatography (HPLC) and that of fluorescein and rhodamine using fluorescence. Dexamethasone corneal adsorption was measured using enzyme-linked immunoabsorbant assay (ELISA). Both acid and alkaline injuries reduced trans-corneal electrical resistance. NaOH injury increased hydrophilic fluorescein penetration (NaOH 8.59 ± 1.50E–05 cm.min −1 vs. Hanks' Balanced Salt Solution (HBSS) 1.64 ± 1.01E–06 cm.min −1 ) with little impact on hydrophobic rhodamine B (1 M NaOH 6.55 ± 2.45E–04 cm.min −1 vs. HBSS 4.60 ± 0.972E–04 cm.min −1 ) and dexamethasone penetration (1 M NaOH 3.00 ± 0.853E–04 cm.min −1 vs. HBSS 2.69 ± 0.439E–04 cm.min −1 ). By contrast, H 2 SO 4 decreased trans-corneal penetration of hydrophilic fluorescein (H 2 SO 4 1.16 ± 14.2E–07 cm.min −1 ) and of hydrophobic dexamethasone (H 2 SO 4 1.88 ± 0.646E–04 cm.min −1 ) and rhodamine B (H 2 SO 4 4.60 ± 1.42E–05 cm.min −1 ). Acid and alkaline OCI differentially disrupted the corneal epithelial barrier function. Acid injury reduced penetration of hydrophobic dexamethasone and rhodamine B as well as hydrophilic fluorescein, which may translate clinically into reduced drug penetration after OCI, while alkaline injury increased fluorescein penetration, with minimal effect on dexamethasone and rhodamine B penetration.

Universal Microcarriers Based on Natural and Synthetic Polymers for Co-Delivery of Hydrophilic and Hydrophobic Compounds

“…Significant loss of protein occurred during carbonate matrix removal with EDTA solution, as well as subsequent washes. These results are in agreement with the data from which demonstrated high efficiency of BSA incorporation into polyelectrolyte microcapsules [ 31 ].…”

“…It is not possible to directly compare these values due to differences in the physico-chemical properties of RBITC and the compounds mentioned above; however, RBITC as a model compound in our studies possessed an important experimental advantage, since it simultaneously served a fluorescent reporter, allowing for reliable quantitation and imaging of its distribution. It has been also used as a model hydrophobic molecule in other similar studies [ 31 , 32 ]. Our initial results are encouraging; however, further studies with hydrophobic drug molecules will allow to better determine the therapeutic potential of our microcapsule design.…”