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

ABSTRACT

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.

KEYWORDS:

• Lanreotide acetate
• ion pairing
• thiol-disulfide exchange reactions
• self nano-emulsifying delivery system
• glutathione

Declaration of interest

All the expenses for this work were supported by the Higher Education Commission of Pakistan (HEC), the Austrian Agency for International Co-operation in Education and Research (ÖAD) and the FWF (Fonds zur Förderung der wissenschaftlichen Forschung) project No. ZFP 235,150. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

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