{"title":"Design of Electrostatic Nanocomplex of Semaglutide with Protamine and Zinc for Subcutaneous Prolonged Delivery.","authors":"In Gyu Yang, Jeong-Soo Kim, Myung Joo Kang","doi":"10.3390/nano15181399","DOIUrl":null,"url":null,"abstract":"<p><p>The aim of this study was to design a poorly water-soluble electrostatic nanocomplex of semaglutide (SMG) with protamine sulfate (PS) and zinc ions (Zn) for prolonged subcutaneous delivery. Complexation of SMG with the cationic peptide PS increased the lipophilicity (logP) proportionally from -4.7 to 0.3, particularly in the presence of Zn. The optimized nanocomplex exhibited spherical morphology, an amorphous state, a particle size of 196.0 nm, and a zeta potential of -45.7 mV. In an in vitro dissolution test under sink conditions, native SMG showed rapid drug release with 98% dissolution within 24 h. In contrast, the nanocomplexes showed markedly delayed release, with a concentration-dependent relationship between PS/Zn contents and SMG release rate, exhibiting 19% drug release over 7 days in the optimized formula. These findings suggest that the proposed nanocomplex is a promising system for long-acting injectable delivery of SMG, potentially enhancing patient compliance in patients with obesity or type 2 diabetes.</p>","PeriodicalId":18966,"journal":{"name":"Nanomaterials","volume":"15 18","pages":""},"PeriodicalIF":4.3000,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12472674/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nanomaterials","FirstCategoryId":"88","ListUrlMain":"https://doi.org/10.3390/nano15181399","RegionNum":3,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
引用次数: 0
Abstract
The aim of this study was to design a poorly water-soluble electrostatic nanocomplex of semaglutide (SMG) with protamine sulfate (PS) and zinc ions (Zn) for prolonged subcutaneous delivery. Complexation of SMG with the cationic peptide PS increased the lipophilicity (logP) proportionally from -4.7 to 0.3, particularly in the presence of Zn. The optimized nanocomplex exhibited spherical morphology, an amorphous state, a particle size of 196.0 nm, and a zeta potential of -45.7 mV. In an in vitro dissolution test under sink conditions, native SMG showed rapid drug release with 98% dissolution within 24 h. In contrast, the nanocomplexes showed markedly delayed release, with a concentration-dependent relationship between PS/Zn contents and SMG release rate, exhibiting 19% drug release over 7 days in the optimized formula. These findings suggest that the proposed nanocomplex is a promising system for long-acting injectable delivery of SMG, potentially enhancing patient compliance in patients with obesity or type 2 diabetes.
期刊介绍：
Nanomaterials (ISSN 2076-4991) is an international and interdisciplinary scholarly open access journal. It publishes reviews, regular research papers, communications, and short notes that are relevant to any field of study that involves nanomaterials, with respect to their science and application. Thus, theoretical and experimental articles will be accepted, along with articles that deal with the synthesis and use of nanomaterials. Articles that synthesize information from multiple fields, and which place discoveries within a broader context, will be preferred. There is no restriction on the length of the papers. Our aim is to encourage scientists to publish their experimental and theoretical research in as much detail as possible. Full experimental or methodical details, or both, must be provided for research articles. Computed data or files regarding the full details of the experimental procedure, if unable to be published in a normal way, can be deposited as supplementary material. Nanomaterials is dedicated to a high scientific standard. All manuscripts undergo a rigorous reviewing process and decisions are based on the recommendations of independent reviewers.
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