Asymmetry in Drug Permeability through the Cornea

Abstract

The permeability through the cornea determines the ability of a drug or any topically applied compound to cross the tissue and reach the intraocular area. Most of the permeability values found in the literature are obtained considering topical drug formulations, and therefore, refer to the drug permeability inward the eye. However, due to the asymmetry of the corneal tissue, outward drug permeability constitutes a more meaningful parameter when dealing with intraocular drug-delivery systems (i.e., drug-loaded intraocular lenses, intraocular implants or injections). Herein, the permeability coefficients of two commonly administered anti-inflammatory drugs (i.e., bromfenac sodium and dexamethasone sodium) were determined ex vivo using Franz diffusion cells and porcine corneas in both inward and outward configurations. A significantly higher drug accumulation in the cornea was detected in the outward direction, which is consistent with the different characteristics of the corneal layers. Coherently, a higher permeability coefficient was obtained for bromfenac sodium in the outward direction, but no differences were detected for dexamethasone sodium in the two directions. Drug accumulation in the cornea can prolong the therapeutic effect of intraocular drug-release systems.

Drug-Loaded Hydrogels for Intraocular Lenses with Prophylactic Action against Pseudophakic Cystoid Macular Edema

“…As the amount of dexamethasone sodium permeated to the receptor chamber was below the HPLC quantification limit, it was not possible to calculate the permeability coefficient for the drug and only the results related to bromfenac sodium are shown ( Supplementary Materials Figure S3 , Table 4 ). The obtained permeability coefficient of bromfenac sodium (17–18 × 10 −7 cm/s) was comparable to previously reported values (≈21 × 10 −7 cm/s) for the free drug solution tested using the same experimental set-up [ 40 ]. Therefore, the permeability coefficients experimentally obtained with free drug solutions are expected to be valid also when hydrogel discs are used as drug carriers.…”

“…The drug permeability through the cornea, P cornea , was required to estimate the drug loss through the tissue. The permeability values of bromfenac sodium and dexamethasone sodium were obtained with ex vivo tests which involved Franz diffusion cells and porcine corneas, as described in a previous publication [ 40 ]. Briefly, corneas were excised with 2–3 mm of surrounding sclera for support and then placed with the endothelium facing the donor chamber of the Franz cell to simulate the in vivo conditions of the tissue when exposed to intraocular drug sources.…”

A Physiology-Based Mathematical Model to Understand Drug Delivery from Contact Lenses to the Back of the Eye

“…The concentration in each tissue is considered independent of the position, as the drug distribution is assumed to be homogeneous. It is further assumed that the mass transfer resistance offered by the corneal endothelium is negligible [ 21 ], thus allowing for the stroma to be lumped together with the aqueous humor in the model, while the corneal epithelium is treated as a separate compartment ( C Ep ). Based on these assumptions, the following equations are obtained for the seven compartments:…”

Skin-on-a-Chip Technology for Testing Transdermal Drug Delivery—Starting Points and Recent Developments

“…The vertically oriented Franz diffusion cell system (Teledyne Hanson Research, Chatsworth, CA, USA) is one of the "gold-standard" methods for the investigation of the transdermal drug delivery, which is suitable for studying artificial membranes and ex vivo skin samples [15,16]. Beside the transdermal route, several examples are known for Franz cell experiments, studying the nasal, corneal as well as the transbuccal administration [10,[17][18][19].…”