Slow Release Coatings for Inhaled Dynorphins

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DESCRIPTION (provided by applicant): Opiate abuse remains a major problem in the United States. NIDA stressed the need for new treatment concepts, such as anti-craving compounds the development of new approaches for the administration of potential addiction treatment drugs with poor bioavailability, such as dynorphins, and the development of controlled release dosage forms for addiction treatment. As a new therapeutic approach to reduce craving, the opioid peptide dynorphin Al-13 (Dyn Al-13) has been suggested, but the clinical outcome has been suboptimal because dynorphins short half-life. To overcome these pharmacokinetic challenges, we propose to administer metabolically more stable dynorphin derivatives in a sustained release fashion using the lung as entry port for improved bioavailability. Therefore drug powders will be coated with biodegradable polymers using a novel pulsed laser deposition based (PLD) coating technique to engineer the necessary sustained release characteristics. The main aim of this Phase I proposal is to prove the concept (I) by identifying PLD conditions that produce coatings with desired release characteristics; (II) characterizing the coated particle with respect to size arid polymer structure; (III) investigating release rate in vitro from selected coating formulations; and (IV) by conducting preliminary pharmacokinetic studies in rats after intratracheally administration of the most promising dynorphin formulation. PROPOSED COMMERCIAL APPLICATION: Not Available