In-situ gel of Povidone Iodine/Budesonide as Sustained Nasal Drug Delivery for the Treatment of Chronic Rhinosinusitis

Abstract SummaryWe propose to develop a long acting in situ gel nasal spray containing povidone iodine in combination with budesonide for the treatment of chronic rhinosinusitisChronic rhinosinusitisCRSis often the result of mixed inflammatory and infectious processes that concurrently affect the nose and para nasal sinusesThe condition is defined by a constellation of symptoms and prolonged clinical courseaffecting as many asmillion US adults per yearPersistence of infection can lead to chronic mucosal inflammationaltered sinonasal ciliary functionand nasal polyp formationThe treatment of multiple drug resistant rhinosinusitis remains largely ineffectiveThe established role of bacterial biofilms in chronic diseasessuch as CRSand their formidable resistance to conventional medical and surgical therapies poses a significant problem to the treating physicianWe had previously developed a novelproprietary irrigation suspensionIVIEWPovidone Iodine combination with budesonidefor the treatment of chronic rhinosinusitisCRSBy employing a non toxichighly biocidal antiseptic with a powerful nasal steroidwe have demonstrated that we can control both infectious and inflammatory aspects of CRSHowevera significant challenge of nasal drug development is to overcome the protective barriers of the nasal cavity without causing permanent tissue damageThe major problems that persist with nasal solutions are cleared off rapidly from nasal cavityBecause human nasal mucosa is covered with approximatelyml mucuswhich consists of sodiumpotassium and calcium ionsa solution gel phase transition can be expected with ion sensitive gel formulations to decrease the mucocilliary clearance and prolong the residence time at the nasal absorption site and thereby facilitate the uptake of the drugWe propose in this SBIR Phase I to optimize an in situ gel forming nasal spray formulation containing both povidone iodine and budesonide by using polysaccharide gel matrixwhere the effective concentrations of drug substances are maintained by the equilibrium between solution drug substances and the gel bound components resulting in a long lastingless toxic pharmacological effectin the mean time to reduce sedimentation of budesonide suspensionDuring the Phase I projectwe will carry out formulation optimizationsstudies of in vitro drug releasedrug retention on nasal mucosaand in vitro antibiofilm studies of IVIEWon established biofilms of Staphylococcus aureusPsuedomonas aeruginosa and Candida Albicans and in vivo animal tolerability and toxicity studiesThe projectandapos s goal is to confirm feasibility of the proposed Phase I projectUpon successful Phase I projectfurther in vivo topical toxicity and efficacy studies of the optimized in situ gel PVP I budesonide formulations will be pursued by a phase II SBIR proposal NarrativeDevelopment of a long acting in situ gel nasal spray containing povidone iodine in combination with budesonide for the treatment of chronic rhinosinusitisrepresents a major advance in rhinologyIf approvedthis will be the first broad spectrum anti infectious drug steroid combination against all causes of pathogens with no drug resistancelong duration in the nasal cavity with better patient compliance and minimized irritation profile