Morris Angie S, Sebag Sara C, Paschke John D, Wongrakpanich Amaraporn, Ebeid Kareem, Anderson Mark E, Grumbach Isabella M, Salem Aliasger K
Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa , 115 South Grand Avenue, S228 PHAR, Iowa City, Iowa 52242, United States.
Department of Internal Medicine, Carver College of Medicine, University of Iowa , 200 Hawkins Drive, Iowa City, Iowa 52242, United States.
Mol Pharm. 2017 Jun 5;14(6):2166-2175. doi: 10.1021/acs.molpharmaceut.7b00114. Epub 2017 May 9.
Asthma is a common lung disease affecting over 300 million people worldwide and is associated with increased reactive oxygen species, eosinophilic airway inflammation, bronchoconstriction, and mucus production. Targeting of novel therapeutic agents to the lungs of patients with asthma may improve efficacy of treatments and minimize side effects. We previously demonstrated that Ca/calmodulin-dependent protein kinase (CaMKII) is expressed and activated in the bronchial epithelium of asthmatic patients. CaMKII inhibition in murine models of allergic asthma reduces key disease phenotypes, providing the rationale for targeted CaMKII inhibition as a potential therapeutic approach for asthma. Herein we developed a novel cationic nanoparticle (NP)-based system for delivery of the potent and specific CaMKII inhibitor peptide, CaMKIIN, to airways.1 CaMKIIN-loaded NPs abrogated the severity of allergic asthma in a murine model. These findings provide the basis for development of innovative, site-specific drug delivery therapies, particularly for treatment of pulmonary diseases such as asthma.
哮喘是一种常见的肺部疾病,全球有超过3亿人受其影响,它与活性氧增加、嗜酸性气道炎症、支气管收缩和黏液分泌有关。将新型治疗药物靶向输送到哮喘患者的肺部可能会提高治疗效果并将副作用降至最低。我们之前证明,钙/钙调蛋白依赖性蛋白激酶(CaMKII)在哮喘患者的支气管上皮中表达并被激活。在过敏性哮喘小鼠模型中抑制CaMKII可减轻关键的疾病表型,这为靶向抑制CaMKII作为哮喘潜在治疗方法提供了理论依据。在此,我们开发了一种基于新型阳离子纳米颗粒(NP)的系统,用于将强效且特异性的CaMKII抑制剂肽CaMKIIN输送到气道。负载CaMKIIN的纳米颗粒减轻了小鼠模型中过敏性哮喘的严重程度。这些发现为开发创新的、位点特异性药物递送疗法提供了基础,特别是用于治疗哮喘等肺部疾病。