Slow Release Coatings for Inhaled Dynorphins

用于吸入强啡肽的缓释涂层

• 批准号: 6404109
• 负责人: Guenther Hochhaus
• 金额: $ 9.97万
• 依托单位: NANOCOAT TECHNOLOGIES
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-15 至 2002-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6404109
• 关键词: biodegradable product; dosage forms; drug design /synthesis /production; dynorphins; inhalation drug administration; laboratory rat; particle; pharmacokinetics; polymers; slow release drug; surface coating

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

描述（由申请人提供）：阿片类药物滥用仍然是一个主要问题， 美国的NIDA强调需要新的治疗概念，例如 反渴望化合物的新方法的发展， 生物利用度差的潜在成瘾治疗药物，如 强啡肽，和控制释放剂型的发展 戒毒治疗作为一种新的治疗方法，以减少渴望， 阿片肽强啡肽Al-13（Dyn Al-13）已被提出，但临床 由于强啡肽的半衰期短，结果不理想。克服 这些药代动力学的挑战，我们建议给予代谢更多 以持续释放方式使用肺作为 提高生物利用度的入口。因此，药物粉末将被包覆 与可生物降解的聚合物，使用一种新的脉冲激光沉积（PLD） 包衣技术，以设计必要的持续释放特性。 第一阶段提案的主要目的是通过以下方式证明概念（I） 确定产生具有所需释放的涂层的PLD条件 （II）表征包覆颗粒的尺寸 （III）研究体外释放速率， 包衣制剂;和（IV）通过进行初步药代动力学 在大鼠中进行的研究中， 强啡肽制剂。 拟定商业应用： 不可用

项目成果

Stabilized dynorphin derivatives for modulating antinociceptive activity in morphine tolerant rats: effect of different routes of administration.

用于调节吗啡耐受大鼠的抗伤害活性的稳定强啡肽衍生物：不同给药途径的效果。

• DOI: 10.1208/aapsj060436
• 发表时间: 2004
• 期刊: The AAPS journal
• 作者: Brugos,Brugos;Arya,Vikram;Hochhaus,Guenther
• 通讯作者: Hochhaus,Guenther

Identification of stabilized dynorphin derivatives for suppressing tolerance in morphine-dependent rats.

鉴定用于抑制吗啡依赖性大鼠耐受性的稳定强啡肽衍生物。

• DOI: 10.1023/b:pham.0000036920.50291.5b
• 发表时间: 2004
• 期刊: Pharmaceutical research
• 影响因子: 3.7
• 作者: Al-Fayoumi,SulimanI;Brugos,Boglarka;Arya,Vikram;Mulder,Esther;Eppler,Barbel;Mauderli,AndreP;Hochhaus,Günther
• 通讯作者: Hochhaus,Günther