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Oral Delivery of Peptide Formulations and Their Cellular Evaluation

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Abstract

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.

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Abbreviations

CAGR:

Compound annual growth rate

GLP:

Glucagon like peptide

rhPTH:

Human recombinant parathyroid hormone

hGH:

Human growth hormone

MIRA:

Metal ions and reducing agents

ELISA:

Enzyme-linked immunosorbent assay

NDA:

New drug application

MCC:

Microcrystalline cellulose

UPLC:

Ultra performance liquid chromatography

BABIM:

Amidinobenzimidazole

IG:

Insulin glargine

TP:

Teriparatide

LA:

Leuprolide acetate

LS:

Liraglutide sodium

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Acknowledgements

The authors are thankful to Jubilant Biosys Ltd for carrying the animal studies. The authors are acknowledge Anya Biopharma Inc for funding. The authors are grateful to University Grants Commission for the UGC-SAP fellowship [F.25-1/2014-15(BSR)No.F.8-10/2007(BSR)], Indian Council of Medical Research (ICMR), (No. 3/1/3/JRF-2015/HRD-LS/29/31232/85) and Department of Biotechnology (BT/PR10865/AAQ/3/659/2014), Government of India for fellowship.

Funding

Anya Biopharm, UGC-SAP fellowship [F.25-1/2014-15(BSR)No.F.8-10/2007(BSR)], Indian Council of Medical Research (ICMR), (No. 3/1/3/JRF-2015/HRD-LS/29/31232/85) and Department of Biotechnology (BT/PR10865/AAQ/3/659/2014).

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Author notes

  1. Saurabh Patil and Kritika Gupta have contributed equally.

Authors and Affiliations

  1. Department of Chemical Engineering, Institute of Chemical Technology, N. P. Marg, Matunga, Mumbai, 400019, India

    Saurabh Patil, Ashish Pandit & Ratnesh Jain

  2. Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, N. P. Marg, Matunga, Mumbai, Maharashtra, 400019, India

    Kritika Gupta & Prajakta Dandekar

  3. Anya Biopharm Inc, 6F., No. 378, Changchun Rd., Taipei, 10487, Taiwan

    Bhushan Desai & Siegfried Gschliesser

Authors
  1. Saurabh Patil
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  2. Kritika Gupta
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  3. Ashish Pandit
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  4. Bhushan Desai
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  5. Siegfried Gschliesser
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  6. Prajakta Dandekar
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Contributions

SP, KG and AP contributed in acquisition of data, analysis and interpretation of data. BD and SG contributed to conception and design of the study. PD and RJ contributed in drafting the article or revising it critically for important intellectual content.

Corresponding authors

Correspondence to Prajakta Dandekar or Ratnesh Jain.

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The authors have no competing interest.

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Ethical approval was taken by Jubilant Biosys Ltd from appropriate ethical committee for conducting animal studies.

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Patil, S., Gupta, K., Pandit, A. et al. Oral Delivery of Peptide Formulations and Their Cellular Evaluation. Int J Pept Res Ther 27, 2831–2844 (2021). https://doi.org/10.1007/s10989-021-10293-x

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