Oral Delivery of Peptide Formulations and Their Cellular Evaluation

• Published in: International journal of peptide research and therapeutics Vol. 27; no. 4; pp. 2831 - 2844
• Main Authors: Patil, Saurabh, Gupta, Kritika, Pandit, Ashish, Desai, Bhushan, Gschliesser, Siegfried, Dandekar, Prajakta, Jain, Ratnesh
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01-12-2021; Springer Nature B.V
• Subjects: Animal Anatomy; Bioavailability; Biochemistry; Biomedical and Life Sciences; Blood levels; Enzymatic activity; Gastrointestinal tract; Histology; Insulin; Intravenous administration; Life Sciences; Molecular Medicine; Morphology; Oral administration; P-Glycoprotein; Parathyroid hormone; Peptides; Pharmaceutical Sciences/Technology; Pharmacology/Toxicology; Polymer Sciences; Proteolysis; Proteolytic enzymes; Reducing agents; Enzyme activity; Oral; Bioavailability; Enzyme; Peptide
• ISSN: 1573-3149; 1573-3904
• DOI: 10.1007/s10989-021-10293-x

The development of peptide-based formulations presents numerous challenges to the formulator due to their complexity, delicate structure and sensitivity towards external environment factors. To date, the commonly employed routes for delivering peptide based formulations are intramuscular, intravenous and subcutaneous routes. Though oral route enables improved patient compliance and ease of administration, it remains still unexplored due to enzymatic degradation of peptides in the gastrointestinal tract and their poor permeation across the intestinal epithelial membrane. In the present study, we have developed a novel systemic approach for novel delivery of therapeutic peptides. Insulin glargine, teriparatide, liraglutide, leuprolide were used as model oral peptides. The peptide granules were formulated with various combinations of metal inhibitors, reducing agents, p-glycoprotein inhibitors and permeation enhancers and administered orally to animals using enteric coated capsules. Enzyme activity for proteolytic enzymes was assessed, also blood plasma concentration and bioavailability of peptides obtained from the animal study were compared to commercial formulations.
Graphic Abstract