Optimization of hyaluronan-based eye drop formulations

Abstract

Hyaluronan (HA) is frequently incorporated in eye drops to extend the pre-corneal residence time, due to its viscosifying and mucoadhesive properties. Hydrodynamic and rheological evaluations of commercial products are first accomplished revealing molecular weights varying from about 360 to about 1200 kDa and viscosity values in the range 3.7–24.2 mPa s. The latter suggest that most products could be optimized towards resistance to drainage from the ocular surface. Then, a study aiming to maximize the viscosity and mucoadhesiveness of HA-based preparations is performed. The effect of polymer chain length and concentration is investigated. For the whole range of molecular weights encountered in commercial products, the concentration maximizing performance is identified. Such concentration varies from 0.3 (wt%) for a 1100 kDa HA up to 1.0 (wt%) for a 250 kDa HA, which is 3-fold higher than the highest concentration on the market. The viscosity and mucoadhesion profiles of optimized formulations are superior than commercial products, especially under conditions simulating in vivo blinking. Thus longer retention on the corneal epithelium can be predicted. An enhanced capacity to protect corneal porcine epithelial cells from dehydration is also demonstrated in vitro. Overall, the results predict formulations with improved efficacy.

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Optimization of hyaluronan-based eye drop formulations
Rosanna Salzillo, Chiara Schiraldi, , Luisana Corsuto, Antonella D’Agostino, Rosanna Filosa, Mario De Rosa, Annalisa La Gatta,
Department of Experimental Medicine, Section of Biotechnology, Medical Histology and Molecular Biology, Bioteknet Second University of Naples, Via L. De Crecchio 7, 80138 Naples, Italy
Received 26 April 2016, Revised 22 July 2016, Accepted 25 July 2016, Available online 29 July 2016
doi:10.1016/j.carbpol.2016.07.106
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