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Propionate-functionalized chitosan hydrogel nanoparticles for effective oral delivery of insulin
Oral delivery of macromolecular drugs is often hampered by the harsh gastrointestinal environment, which makes the drugs have poor bioavailability. Insulin, the most used drug for diabetes, also faces the same challenge for oral administration. Hence, we decorated microbial metabolite propionate on chitosan (CS) to fabricate insulin-loaded propionate-modified CS hydrogel nanoparticles (IN-CS/PA HNPs). The prepared IN-CS/PA HNPs exhibited high encapsulation efficiency (> 95 %) and loading capacity (∼10 %) for insulin. The system provided better protection for insulin in gastrointestinal environment compared to unmodified IN-CS HNPs. Moreover, the active functional group of propionate can be recognized and transported by mono-carboxylate transporter protein 1 (MCT1) targeting. Thus, in both Caco-2 cells and the ligated intestinal loops of rats, IN-CS/PA HNPs significantly improved permeability and uptake of insulin on intestinal epithelium, which was attributed to MCT1-mediat ed endocytosis. In type 1 diabetic (T1D) rats, oral delivery of IN-CS/PA HNPs with 60 IU/kg insulin led to more stable and long-lasting hypoglycemic effect than a 5 IU/kg dose of subcutaneously injected insulin. It also generated 2.29-fold and 11.88-fold higher relative oral bioavailability compared with empty IN-CS HNPs and free insulin, respectively. This study demonstrated that propanoic acid-functionalized chitosan hydrogel nanoparticles could improve the oral absorption of insulin by overcoming multiple barriers in gastrointestinal tract, providing a promising active targeting strategy for the oral delivery of macromolecules drugs. © 2024
Authors : Chen Y.; Song H.; Wang X.; Huang R.; Li S.; Guan X.
Source : Elsevier B.V.
Article Information
| Year | 2025 |
| Type | Article |
| DOI | 10.1016/j.ijbiomac.2024.139159 |
| ISSN | 01418130 |
| Volume | 291 |
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