title: Characterization of the pH and Temperature in the Rabbit, Pig, and Monkey Eye: Key Parameters for the Development of Long-Acting Delivery Ocular Strategies.
abstract: Many long-acting delivery strategies for ocular indications rely on pH- and/or temperature-driven release of the therapeutic agent and degradation of the drug carrier. Yet, these physiological parameters are poorly characterized in ocular animal models. These strategies aim at reducing the frequency of dosing, which is of particular interest for the treatment of chronic disorders affecting the posterior segment of the eye, such as macular degeneration that warrants monthly or every other month intravitreal injections. We used anesthetized white New Zealand rabbits, Yucatan mini pigs, and cynomolgus monkeys to characterize pH and temperature in several vitreous locations and the central aqueous location. We also established post mortem pH changes in the vitreous. Our data showed regional and species differences, which need to be factored into strategies for developing biodegradable long-acting delivery systems.
authors.affiliation: Genentech Safety Assessment , 1 DNA Way, South San Francisco, California 94080, United States.
authors.forename: Florence
authors.initials: F
authors.lastname: Lorget
authors.affiliation: CiToxLAB North America , Laval, Quebec, H7V 4B3, Canada.
authors.forename: Audrey
authors.initials: A
authors.lastname: Parenteau
authors.affiliation: Faculté de médecine vétérinaire, University of Montreal , Saint-Hyacinthe, Quebec, J2S 2M2, Canada.
authors.forename: Michel
authors.initials: M
authors.lastname: Carrier
authors.affiliation: CiToxLAB North America , Laval, Quebec, H7V 4B3, Canada.
authors.forename: Daniel
authors.initials: D
authors.lastname: Lambert
authors.affiliation: CiToxLAB North America , Laval, Quebec, H7V 4B3, Canada.
authors.forename: Ana
authors.initials: A
authors.lastname: Gueorguieva
authors.affiliation: Genentech Safety Assessment , 1 DNA Way, South San Francisco, California 94080, United States.
authors.forename: Chris
authors.initials: C
authors.lastname: Schuetz
authors.affiliation: Genentech Safety Assessment , 1 DNA Way, South San Francisco, California 94080, United States.
authors.forename: Vlad
authors.initials: V
authors.lastname: Bantseev
authors.affiliation: Genentech Safety Assessment , 1 DNA Way, South San Francisco, California 94080, United States.
authors.forename: Evan
authors.initials: E
authors.lastname: Thackaberry
mesh_terms: D000777:Anesthetics / Q000627:therapeutic use; D000818:Animals; D000882:Haplorhini; D006863:Hydrogen-Ion Concentration; D058449:Intravitreal Injections / Q000379:methods; D008252:Macaca fascicularis; D008297:Male; D023421:Models, Animal; D011817:Rabbits; D013552:Swine; D013696:Temperature; D014822:Vitreous Body / Q000378:metabolism*
chemical_list: D000777:Anesthetics
keywords: aqueous; monkey; pH; pig; rabbit; temperature; vitreous