期刊
INTERNATIONAL JOURNAL OF PHARMACEUTICS
卷 583, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.ijpharm.2020.119357
关键词
Type 2 diabetes mellitus; Insulin resistance; Adiponectin; Gene therapy; Chitosan nanoparticles
资金
- National Institutes of Health [R15GM114701]
- North Dakota Established Program to Stimulate Competitive Research seed funds [FAR0030636]
Global rise in obesity-associated type 2 diabetes mellitus (T2DM) has led to a major healthcare crisis. Development of efficient treatments to treat the underlying chronic inflammation in obesity-associated T2DM, is an unmet medical need. To this end, we have developed a plasmid adiponectin (pADN) based nanomedicine for the treatment of insulin resistance in type 2 diabetes mellitus. Adiponectin is a potent anti-inflammatory/anti-diabetic adipokine, which is downregulated in obesity. In this study, nanomicelles comprising chitosan conjugated to oleic acid and adipose homing peptide (AHP) were developed to deliver pADN to adipocytes. Cationic chitosan-oleic-AHP micelles were 112 nm in size, encapsulated 93% of pADN and protected gene cargo from DNase I mediated enzymatic degradation. In vitro, the nanomicellar formulation significantly increased adiponectin production compared to free plasmid as well as standard transfecting agent FuGENE(R)HD. Single dose subcutaneous administration of pADN-chitosan-oleic-AHP to obese-diabetic rats, resulted in improved insulin sensitivity for up to 6 weeks, which matched the glucose disposal ability of healthy rats. Serum adiponectin level in pADN-chitosan-oleic-AHP treated rats was comparable to healthy rats for up to 3 weeks post treatment. Overall, the results indicate that pADN-chitosan-oleic-AHP based therapy is a promising treatment approach for obesity-associated T2DM.
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