Oral Delivery of Proteins and Peptides: Concepts and Applications - Challenges in Delivery of Therapeutic Genomics and Proteomics - page 477

10

Oral Delivery of Proteins
and Peptides: Concepts and
Applications

Gaurang Patel, Ambikanandan Misra
Pharmacy Department, TIFAC - Centre of Relevance and Excellence
in New Drug Delivery Systems, The Maharaja Sayajirao University of
Baroda, PO Box 51, Kalabhavan, Vadodara 390 001, Gujarat, India

10.1 Introduction

Recombinant deoxyribonucleic acid (DNA) techniques have eased the commercial
scale production of proteins and peptides and thus the number of protein drugs has
been increased exponentially [1] . Pharmacological classes such as enzymes (e.g., tis-
sue plasminogen activator), enzyme inhibitors (i.e., peptide inhibitor of angiotensin I),
hormones (e.g., leutinizing hormone-releasing hormone, LHRH), immunomodulators
(e.g., interferons, vaccines), and antimicrobial agents (e.g., phylloxin) include proteins
or peptides as a drug substance. Although the therapeutic potential and specificity of
proteins are well recognized, their use in therapies is still limited due to their low bio-
availability via noninvasive routes [2] . Currently, proteins and peptides are adminis-
tered only through the parenteral route. Significant efforts have been made to explore
other noninvasive routes, including oral, buccal, nasal, pulmonary, vaginal, rectal, ocu-
lar, and transdermal, because of the limitations of the parenteral route, that is, frequent
dosing due to the short half-life of protein and peptide in blood, pain on administration,
poor patient compliance, and sterility requirement [3-5] .
Delivery of peptides, such as LHRH and calcitonin through the nasal route, has
already been studied and has showed the advantage of high permeability of proteins
and peptides across nasal mucosa. Chronic or prolonged use of the dosage form in
the nasal cavity is associated with disadvantages such as potential irritation and tox-
icity to ciliary cells. Variable mucus secretion among patients affects the residence
time and absorption through mucosa [6] . Delivery of proteins and peptides across the
vaginal and the rectal mucosa has poor patient compliance [7] . Due to disadvantages
of other mucosa, much attention is paid to mucosa of the oral cavity, such as buccal,
gingival, and sublingual regions, and small and large intestinal mucosa for systemic
delivery of proteins and peptides [8] .
Mucosa of the oral cavity has several positive features, including excellent acces-
sibility, high patient acceptance and compliance, and significant robustness of the
mucosa. Without the assistance of trained personnel, the patient can self-administer the