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Int J Nanomedicine. 2013;8:23-32. doi: 10.2147/IJN.S38507. Epub 2012 Dec 28.

Nanoemulsions coated with alginate/chitosan as oral insulin delivery systems: preparation, characterization, and hypoglycemic effect in rats.

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  • 1Key Laboratory of Smart Drug Delivery of Ministry of Education and People's Liberation Army (PLA), School of Pharmacy, Fudan University, Shanghai, China.

Abstract

This study aimed to prepare nanoemulsions coated with alginate/chitosan for oral insulin delivery. Uncoated nanoemulsions were prepared by homogenization of a water in oil in water (w/o/w) multiple emulsion that was composed of Labrafac(®) CC, phospholipid, Span™ 80 and Cremorphor(®) EL. Coating of the nanoemulsions was achieved based on polyelectrolyte cross-linking, with sequential addition of calcium chloride and chitosan to the bulk nanoemulsion dispersion that contained alginate. The particle size of the coated nanoemulsions was about 488 nm and the insulin entrapment ratio was 47.3%. Circular dichroism spectroscopy proved conformational stability of insulin against the preparative stress. In vitro leakage study indicated well-preserved integrity of the nanoemulsions in simulated gastric juices. Hypoglycemic effects were observed in both normal and diabetic rats. The relative pharmacological bioavailability of the coated nanoemulsion with 25 and 50 IU/kg insulin were 8.42% and 5.72% in normal rats and 8.19% and 7.84% in diabetic rats, respectively. Moreover, there were significantly prolonged hypoglycemic effects after oral administration of the coated nanoemulsions compared with subcutaneous (sc) insulin. In conclusion, the nanoemulsion coated with alginate/chitosan was a potential delivery system for oral delivery of polypeptides and proteins.

KEYWORDS:

alginate; chitosan; insulin; nanoemulsion; oral delivery

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