Novel Extended Release Povidone Iodine Ophthalmic Drop for Viral Conjunctivitis

Abstract Summary We propose to develop a long acting in situ hydrogel povidone iodine drop for the treatment of active infections of the conjunctiva and cornea by bacteria mycobacteria virus fungus or amoebic causes There is currently no broadly effective therapy that treats all causes of infection and nothing is approved for the treatment of viral conjunctivitis This represents a massive unmet need in ophthalmology Acute conjunctivitis pink eye is one of the most common and most contagious ocular infections seen in the United States Japan and Europe Approximately percent of infectious conjunctivitis cases have a viral etiology and to percent of these are caused by adenovirus Viral conjunctivitis is highly infectious and transmissible causing lost work and school days as well as increased healthcare costs and risks from unnecessary antibiotic prescriptions There are million cases of infectious conjunctivitis annually in the United States and approximately million cases in the EU annually Povidone iodine PVP I is a commercially available iodophor routinely used in ophthalmology and general surgery Povidone iodine solutions have been proven effective before solution and after ocular surgery at birth and for active infections PVP I is the only agent known to prevent post op endophthalmitis Solutions of PVP I are toxic to viruses including HIV fungi parasites and bacteria with no known development of resistance It is well described in the literature that aqueous PVP I solutions exhibit greater antiseptic efficacy at lower concentrations Furthermore these lower concentrations are less irritating to the eyes ears and skin We propose to develop an in situ gel formulation where the effective concentration of PVP I is maintained by the equilibrium between solution PVP I and the gel bound components resulting in a long lasting less toxic pharmacological effect The goal of the project is to optimize stable hydrogel PVP I formulations that have acceptable gel strength slow releasing properties and are non irritating to the eye We designed a screening model for measuring gel matrix Viscosity vs Concentrations of gel matrix at and also under physiological conditions by the addition of simulated tear fluid STF This method will be used to select the gel matrix with the largest viscosity value for optimization of gel strength and clarity of the in situ gel PVP I formulations We have discovered the in situ gel forming povidone iodine compositions can be formulated with one or more ion sensitive in situ gel forming materials such as polysaccharides which successfully overcome PVP I s inability to form in situ gel in common slow release polymers Ocular residence time of the drug will be determined in NZW rabbits by measuring continuous florescence on corneal surface with coumarin labeled drug solution vs control studies Irritation studies in NZW rabbits are planned to confirm minimized irritation of such formulations to the eye In vitro antibacterial fungi and anti viral studies are planned to demonstrate in situ gel PVP I formulations broad spectrum efficacy Upon successful studies for Optimization of in situ gel PVP I formulations and confirmation of their in vitro efficacies further in vivo topical toxicity and efficacy studies and proof of concept clinical development of the optimized in situ gel PVP I formulations will be pursued by a phase II SBIR proposal Narrative Development of a broad spectrum anti infective treatment for acute conjunctivitis Pink Eye including viral conjunctivitis represents a major advance for a massive unmet need in ophthalmology We propose to develop a stable non irritating in situ gel povidone iodine ophthalmic drop with long acting anti bacterial anti fungi and anti viral effects