{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T15:07:40Z","timestamp":1778166460004,"version":"3.51.4"},"reference-count":51,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T00:00:00Z","timestamp":1768176000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Anhui Province University Talent Project","award":["2024jsqygz61"],"award-info":[{"award-number":["2024jsqygz61"]}]},{"name":"Wannan Medical College Scientific Research Project","award":["WYRCQD2023035"],"award-info":[{"award-number":["WYRCQD2023035"]}]},{"name":"The Provincial Quality Project for Cultivating New Era Talents","award":["2024yjsxxsfkc044"],"award-info":[{"award-number":["2024yjsxxsfkc044"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background: Oral insulin improves compliance and convenience in patients with diabetes who require regular needle injections. However, the clinical application of oral insulin preparations has been limited due to instability and inefficient permeation through the gastrointestinal tract. In this study, a novel cationic polysaccharide nanodrug delivery platform was designed for efficient oral insulin delivery. Methods: The innovative thiolated trimethyl chitosan-grafted \u03b2-cyclodextrin (NCT) was synthesized by utilizing N-trimethyl chitosan (TMC) as the polymer backbone. This involved modifying TMC with thiol group-containing N-acetylcysteine and carboxymethyl-\u03b2-cyclodextrin that possesses hydrophobic cavities via an amide condensation reaction. Subsequently, this polymer was employed to construct the NCT nanoparticle system using an ionic cross-linking method. The physicochemical properties of the NCT nanoparticles were systematically analyzed, and their therapeutic efficacy was comprehensively evaluated in streptozotocin (STZ)-induced animal models. Results: The NCT nanoparticles demonstrated mucus adhesion, permeability, and pH sensitivity, which facilitated a slow and controlled release within the gastrointestinal microenvironment due to both ionic electrostatic interactions and disulfide bonding interactions. The experiments revealed in vivo that insulin\/NCT nanoparticles extended the retention time of insulin in the small intestine. Blood glucose levels decreased to approximately 39% of the initial level at 5 h post-administration while exhibiting smooth hypoglycemic efficacy. Simultaneously, insulin bioavailability increased to 12.58%. Conclusions: The NCT nanoparticles effectively protect insulin from degradation in the gastrointestinal microenvironment while overcoming intestinal barriers, thereby providing a promising approach to oral biomolecule delivery.<\/jats:p>","DOI":"10.3390\/pharmaceutics18010097","type":"journal-article","created":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T10:25:23Z","timestamp":1768213523000},"page":"97","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Efficient Oral Insulin Delivery Through Thiolated Trimethyl Chitosan-Grafted \u03b2-Cyclodextrin Nanoparticles"],"prefix":"10.3390","volume":"18","author":[{"given":"Lizhen","family":"Yu","sequence":"first","affiliation":[{"name":"Anhui Provincial Key Laboratory for Conservation and Exploitation of Biological Resources, School of Life Science, Anhui Normal University, Wuhu 241000, China"},{"name":"School of Pharmacy, Wannan Medical College, Wuhu 241000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fengge","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Wannan Medical College, Wuhu 241000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuyun","family":"Bao","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Wannan Medical College, Wuhu 241000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yue","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Wannan Medical College, Wuhu 241000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuebin","family":"Shen","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Wannan Medical College, Wuhu 241000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Desheng","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Wannan Medical College, Wuhu 241000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhisheng","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Wannan Medical College, Wuhu 241000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinyi","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Wannan Medical College, Wuhu 241000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lihua","family":"Li","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Wannan Medical College, Wuhu 241000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Renmin","family":"Gong","sequence":"additional","affiliation":[{"name":"Anhui Provincial Key Laboratory for Conservation and Exploitation of Biological Resources, School of Life Science, Anhui Normal University, Wuhu 241000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1038\/s41574-024-00993-x","article-title":"Diabetes mellitus in patients with acromegaly: Pathophysiology, clinical challenges and management","volume":"20","author":"Esposito","year":"2024","journal-title":"Nat. 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