pH-sensitive chitosan-deoxycholic acid/alginate nanoparticles for oral insulin delivery

Abstract

Oral absorption of peptides/proteins is usually compromised by various gastrointestinal tract barriers. To improve delivery efficiency, chitosan-conjugated deoxycholic acid (CS-DCA) coupled with sodium alginate (ALG) was prepared to load insulin into pH-sensitive nanoparticles. The insulin-loaded chitosan-deoxycholic acid/alginate nanoparticles (CDA NPs) were characterized by size (143.3 ± 10.8 nm), zeta potential (19.5 ± 1.6 mV), entrapment efficiency (61.14 ± 1.67%), and insulin drug loading (3.36 ± 0.09%). The CDA NPs exhibited pH-triggered release characteristics in vitro and protected the wrapped insulin from gastric degradation. Stability of the CDA NPs in enzyme-containing simulated gastrointestinal fluids suggested that the NPs could partially protect the wrapped insulin from enzymatic degradation. Additionally, CS-DCA-modified NPs promoted the permeability of Caco-2 cells and enhanced intracellular absorption of FITC-labeled insulin by 9.4 and 1.2-folds, when compared to insulin solution and unmodified NPs, respectively. The positively charged NPs increased intestinal villi adhesion and enhanced insulin absorption in the intestines of diabetic rat models. Furthermore, the hypoglycemic test showed that CDA NPs prolonged insulin release in vivo and exerted a remarkable hypoglycemic effect on diabetic rats with an oral bioavailability of 15%. In conclusion, CDA NPs is a potential oral insulin delivery system.

Keywords:

• Nanoparticles
• pH-sensitive
• deoxycholic acid
• oral insulin delivery
• cellular internalization

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by the Natural Science Foundation of Zhejiang Province, China [LQY18H300002], the Medical and Health Technology Project of Zhejiang Province, China [2019KY062 and 2018KY349], the Special project of Zhejiang Academy of Medical Sciences, and Key Laboratory of Neuropsychiatric Drug Research of Zhejiang Province [2019E10021].