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

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.

Integrity and stability of oral liposomes containing bile salts studied in simulated and ex vivo gastrointestinal media.

The objective of this study was to investigate the integrtity and stability of oral liposomes containing glycocholate (SGC-Lip) in simulated gastrointestinal (GI) media and ex vivo GI media from rats in comparison with conventional liposomes (CH-Lip) composed of soybean phosphatidylcholine and cholesterol. Membrane integrity of liposomes was evaluated by monitoring calcein release, particle size and distribution in different simulated GI media. The stability of liposomes encapsulating insulin was investigated in simulated GI fluids containing pepsin or pancreatin and ex vivo GI enzyme fluids. Simulated GI media with low pH or physiological bile salts resulted in significant increase in calcein release, but dynamic laser scattering data showed that the size and distribution were generally stable. SGC-Lip retained the major amount of the initially encapsulated insulin as compared with CH-Lip in simulated GI fluids (SGF, FaSSGF, SIF and FeSSIF-V2). SGC-Lip retained respectively 17.1% and 20.5% of the initially encapsulated insulin in ex vivo GI fluid, which were also significantly more than CH-Lip. These results suggested that SGC-Lip could protect insulin from degradation to some degree during their transit through the gastrointestinal tract and contributed to enhanced oral absorption.