Abstract
The aim of the study was the evaluation of the suitability of 5-oxo-2-pyrrolidinecarboxylic acid (PCA), also in combination with hyaluronic acid (HA), as artificial tears for treatment of dry eye syndrome (DES). Different aqueous formulations containing 0.10% w/w of PCA were used to determine: (i) ex vivo permeation profile of PCA in isolated rabbit corneas; (ii) in vivo residence time of PCA in the precorneal area of rabbits; and (iii) in vivo ability of PCA to counteract the reduction of tear production in an experimental model of DES induced in rabbits. The pharmacokinetic profile of PCA in tear fluid was characterized by high concentrations immediately after application, followed by a rapid decrease, with half-life values of 17.16 and 22.27 min for solutions containing PCA alone and in combination with HA, respectively, when 100 µL of solutions were instilled. The addition of HA almost doubled the PCA bioavailability minimizing the ex vivo apparent corneal permeability of PCA. A positive Shirmer Test Score (STS) was observed for PCA compared to contralateral eyes at all days of treatment for PCA/HA formulation. PCA provides protection from desiccation probably for its osmoprotective activity and high water–binding capability, and this behaviour was enhanced by HA.
Highlights
Dry eye syndrome (DES) is one of the most frequent ophthalmic pathologies and is generally characterized by an insufficient production or a scarce quality of tear secretion
The apparent corneal permeability coefficients (Papp) of pyrrolidinecarboxylic acid (PCA) were calculated from the slope of the steady state from the linear plots of the amount of PCA permeated through the isolated corneas in the receiving chamber (Q) versus time (t) during the ex vivo corneal permeation study
The paerpmpeabreilnityt icsoarnnienatrlinpsiecrmeability (Papp) was defined by the equation Papp = ∆Q/(∆t × C0 × A), where A is the corneal surface in contact with the donor phase and C0 is the concentration of PCA in the donor phase at the beginning of the permeation experiment
Summary
Dry eye syndrome (DES) is one of the most frequent ophthalmic pathologies and is generally characterized by an insufficient production or a scarce quality of tear secretion. This un-physiological condition causes a persistent dryness of the cornea and conjunctiva, as well as a keratoconjunctival disorder responsible for opacity of the cornea, anomalies in vision, and discomfort [1,2,3,4,5,6,7]. High values of osmolarity can be provoked by a reduced aqueous tear flow and/or an increase in the evaporation of the aqueous component of tear fluid, due essentially to a deficiency in the lipid constituent. The use of hypotonic tear substitutes is the most common approach to reduce the ocular discomfort, even if these have a short residence time in the eye
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