1. Academic Validation
  2. Improved oral delivery of insulin by PLGA nanoparticles coated with 5 β-cholanic acid conjugated glycol chitosan

Improved oral delivery of insulin by PLGA nanoparticles coated with 5 β-cholanic acid conjugated glycol chitosan

  • Biomed Mater. 2021 Oct 12;16(6). doi: 10.1088/1748-605X/ac2a8c.
Weizhi Wang 1 2 Chenggong Yu 2 Fangfang Zhang 1 Yuxuan Li 2 Bo Zhang 2 Jie Huang 2 Zhijun Zhang 2 Liang Jin 1
Affiliations

Affiliations

  • 1 State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drugability of Biopharmaceuticals, School of Life Science and Technology, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, Jiangsu 210009, People's Republic of China.
  • 2 CAS Key Laboratory of Nano-Bio Interface, Division of Nanobiomedicine, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou 215123, People's Republic of China.
Abstract

Oral Insulin has been regarded as the best alternative to Insulin injection in therapy of diabetes because of its convenience and painlessness. However, several obstacles in the gastrointestinal tract, such as gastric acid and Enzyme, greatly reduce the bioavailability of oral Insulin. Herein, we report design and preparation of poly (d, l-lactic-co-glycolic acid) nanoparticles (PLGA NPs) coated with 5β-cholanic acid modified glycol chitosan (GC-CA) (GC-CA@PLGA NPs) to improve the oral delivery of Insulin. The GC-CA@PLGA NPs with the size of (302.73 ± 5.13 nm) and zeta potential of (25.03 ± 0.31 mV) were synthesized using the double-emulsion method. The insulin-loading capacity and encapsulation efficiency were determined to be 5.77 ± 0.58% and 51.99 ± 5.27%, respectively. Compared with GC-modified PLGA NPs (GC@PLGA NPs) and bare PLGA NPs, the GC-CA@PLGA NPs showed excellent stability and uptake by Caco-2 cells after simulated gastric acid digestion. Further experiment suggests good biocompatibility of GC-CA@PLGA NPs, including hemolysis and cytotoxicity. Inin vivoexperiment, the Insulin loaded in the GC-CA@PLGA NPs exhibited a long-term and stable release profile for lowering blood glucose and presented 30.43% bioavailability in oral administration. In brief, we have developed an efficient and safe Drug Delivery system, GC-CA@PLGA NPs, for significantly improved oral administration of Insulin, which may find potential application in the treatment of diabetes.

Keywords

PLGA; glycol chitosan; insulin; nanoparticle; oral delivery.

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