title: 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 1200kDa and viscosity values in the range 3.7-24.2mPa 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 1100kDa HA up to 1.0 (wt%) for a 250kDa 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.
authors: 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.
authors: Rosanna
authors: R
authors: Salzillo
authors: 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. Electronic address: chiara.schiraldi@unina2.it.
authors: Chiara
authors: C
authors: Schiraldi
authors: 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.
authors: Luisana
authors: L
authors: Corsuto
authors: 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.
authors: Antonella
authors: A
authors: D'Agostino
authors: 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.
authors: Rosanna
authors: R
authors: Filosa
authors: 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.
authors: Mario
authors: M
authors: De Rosa
authors: 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. Electronic address: annalisa.lagatta@unina2.it.
authors: Annalisa
authors: A
authors: La Gatta
mesh_terms: D000818:Animals; D001704:Biopolymers / Q000737:chemistry* / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D019573:Epithelium, Corneal / Q000187:drug effects*; D006820:Hyaluronic Acid / Q000737:chemistry* / Q000494:pharmacology; D057446:Hydrodynamics; D008970:Molecular Weight; D009883:Ophthalmic Solutions / Q000737:chemistry* / Q000494:pharmacology; D012212:Rheology; D013552:Swine; D014783:Viscosity
chemical_list: D001704:Biopolymers; D009883:Ophthalmic Solutions; D006820:Hyaluronic Acid
keywords: Corneal epithelial cells; Eye drops; Hyaluronan; Mucoadhesiveness; Viscosity