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The binary and tertiary complex based on short-chain glucan and proanthocyanidins for oral insulin delivery Na Ji, Yan Hong, Zhengbiao Gu, Li Cheng, Zhaofeng Li, and Caiming Li J. Agric. Food Chem., Just Accepted Manuscript • DOI: 10.1021/acs.jafc.7b03465 • Publication Date (Web): 19 Sep 2017 Downloaded from http://pubs.acs.org on September 20, 2017
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Journal of Agricultural and Food Chemistry is published by the American Chemical Society. 1155 Sixteenth Street N.W., Washington, DC 20036 Published by American Chemical Society. Copyright © American Chemical Society. However, no copyright claim is made to original U.S. Government works, or works produced by employees of any Commonwealth realm Crown government in the course of their duties.
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Journal of Agricultural and Food Chemistry
The binary and tertiary complex based on short-chain glucan and proanthocyanidins for oral insulin delivery Na Ji†‡
Yan Hong†‡* Zhengbiao Gu†‡* Li Cheng†‡ Zhaofeng Li†‡ Caiming Li†‡
† State Key Laboratory of Food Science and Technology, and ‡ School of Food Science and Technology, Jiangnan University, Wuxi 214122, People’s Republic of China *Correspondence
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Journal of Agricultural and Food Chemistry
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ABSTRACT: The present study was performed to investigate binary and tertiary nanocomposites
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between short-chain glucan (SCG) and proanthocyanidins (PAC) for the oral delivery of insulin.
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There was a large decrease in fluorescence intensity of insulin in the presence of SGC or the
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combination of SGC with PAC. Fourier transform infrared spectroscopy revealed that the binary
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and tertiary nanocomposites were synthesized due to the hydrogen bonding and hydrophobic
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interactions. The insulin entrapped in the nanocomposites was in an amorphous state confirmed by
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X-ray diffraction. Cell culture demonstrated that both the nanocomposites showed no detectable
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cytotoxicity with relative cell viability all above 85%. The pharmacological bioavailability after
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oral administration of insulin-SCG-PAC at a dose of 100 IU/kg was found to be 6.98±1.2% in
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diabetic rats without any sharp fluctuations in 8 h.
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KEYWORDS: Nanocomposites; In vivo; Hypoglycemic effect; Bioavailability
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Journal of Agricultural and Food Chemistry
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INTRODUCTION
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Diabetes mellitus is a chronic metabolic disease and has become an epidemic worldwide.1
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Insulin is a 51 amino acid peptide and, is used in the treatment of diabetes mellitus.2 Ordinarily,
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diabetics must endure 2–4 daily subcutaneous injections of insulin that are associated with trauma,
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local infection, stress, pain, and needle phobia, which can result in poor patient compliance.3-4
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Unlike subcutaneous insulin, oral insulin passes through the portal circulation like endogenous
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insulin, thereby reducing hepatic gluconeogenesis.5 Among the various administration routes, oral
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administration is considered the safest and the most convenient alternative for insulin delivery
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because of its good patient compliance, but it faces important challenges.1, 6-7 The gastrointestinal
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tract presents a natural barrier to the absorption of insulin, which is generally unstable in the harsh
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GI environment, and poorly permeable across biomembranes resulting in
