Development of oral self nano-emulsifying delivery system(s) of lanreotide with improved stability against presystemic thiol-disulfide exchange reactions.

OBJECTIVES: To develop a self nano-emulsifying delivery system (SNEDS) for model peptide lanreotide providing a protective effect towards thiol-disulfide exchange reactions. METHODS: Ion-paired complexes of lanreotide with surfactants were prepared. In the following, Log P (octanol/water) of these complexes was determined. Lanreotide-loaded SNEDS (Lan/Deo-SN2 and Lan/Deo-SN3) were characterized for payload, droplet size and zeta potential. Lan/Deo-SN2 and Lan/Deo-SN3 were incubated with reduced glutathione (GSH) and thiol-enriched casein peptones for the assessment of thiol-disulfide exchange reactions. Ultra-centrifugation was used for separation of lanreotide released from SNEDS. RESULTS: A maximum payload of 6.4% was achieved for Lan/Deo-SN2. Mean droplet size of Lan/Deo-SN2 and Lan/Deo-SN3 was 45 ± 0.20 nm and 37 ± 0.02 nm, respectively. Both formulations showed significant protection towards thiol-disulfide exchange reactions. After 3 h of incubation with GSH, 48% and 80% of lanreotide remained intact when incorporated in Lan/Deo-SN2 and Lan/Deo-SN3, respectively. Furthermore, Lan/Deo-SN2 and Lan/Deo-SN3 showed 47% and 51% protection against thiol enriched casein peptones, respectively. Both formulations showed sustained lanreotide release over a period of 3 h. CONCLUSION: Owing to the results, the above-mentioned approach might be a useful tool to overcome the sulfhydryl barrier of the GI-tract.