Polymeric Nano/Microparticles for Oral Delivery of Proteins and Peptides
Recent advancement in the field of pharmaceutical biotechnology and introduction of recombinant DNA technology have led to the production of a number of therapeutic peptides and proteins for the treatment of several life-threatening diseases (Table 57.1). A number of peptide-based therapeutics such...
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| Published in | Handbook of Encapsulation and Controlled Release pp. 1383 - 1404 |
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| Format | Book Chapter |
| Language | English |
| Published |
CRC Press
2016
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| Subjects | |
| Online Access | Get full text |
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| Summary: | Recent advancement in the field of pharmaceutical biotechnology and introduction of recombinant DNA technology have led to the production of a number of therapeutic peptides and
proteins for the treatment of several life-threatening diseases (Table 57.1). A number of
peptide-based therapeutics such as recombinant hormones, cytokines, vaccines, monoclonal
antibodies, therapeutic enzymes, and the like have been recently approved for clinical use.1
However, most of these peptides are administrated by parenteral route. Inherent short halflives of peptides and chronic therapy requirements in a majority of cases make their repetitive
dosing necessary.2 Frequent injections, oscillating blood drug concentrations, and low patient
acceptability make even the simple parenteral administration of these drugs problematic.3,4
In spite of significant advancement in the field of pharmaceutical research, development of a
proper noninvasive delivery system for peptides remains a distant reality. Although there have
been reports of successful delivery of various peptide therapeutics across nonoral mucosal
routes (such as nasal and buccal), the oral route continues to be the most preferred route for
drug administration.5-7 The oral route, despite enormous barriers that exist in the gastrointestinal tract (GIT), has obvious advantages such as ease of administration, patient compliance,
and cost effectiveness.8,957.1 Introduction ... 1359
57.2Barriers to Oral Delivery of Proteins/Peptides ... 1360
57.3Strategy for Improved Oral Protein Delivery ... 1361
57.4Polymeric Nano/Microparticles as a Possible Oral Peptide-Delivery System ... 136157.4.1Synthetic Biodegradable Polymeric Nano/Microparticles ... 1363
57.4.2 Nonbiodegradable Synthetic Polymers ... 1367
57.4.3Natural and Protein-Based Polymers for Oral Peptide Delivery... 137057.4.3.1Protein-Based Polymers for Oral Protein Delivery ... 1371
57.4.4Preparation of Nano/Microparticles... 137257.4.4.1Nano/Microparticles Obtained by Polymerization of Monomers ... 1372
57.4.4.2 Particles from Preformed Polymers ... 137457.5Concluding Remarks ... 1375
References ... 1375Peptide-based biotechnology products are subject to the same hostile environment faced by all
peptides in the GIT. The major problems associated with oral peptide delivery are the susceptibility
to degradation by the hostile gastric environment; metabolism by luminal, brush border, and
cytosolic peptidases; and poor permeability across the intestinal epithelium because of size,
charge, and hydrophilicity.10,11 Intestinal epithelium serves as a major barrier for the absorption
of orally administered drugs and peptides into the systemic circulation. High-resistance epithelial cell barriers restrict the passage of various hydrophilic compounds from the small intestine
into the human body. The high resistance is due to the formation of well-organized tight junctions that connect the cell plasma membranes by a network of apical localized seams. As the
name implies, tight junctions exclude the paracellular passage of ions, peptides, and proteins.
The paracellular route is the dominant pathway for passive transepithelial solute ow in the
small intestine, and its permeability depends on the regulation of intercellular tight junctions.
The utility of the paracellular route for oral drug delivery has remained unexplored because of a
limited understanding of tight junction physiology and the lack of substances capable of increasing the tight junction permeability without irreversibly compromising intestinal integrity and
function. The attempts made so far to nd ways to increase paracellular transport by loosening
intestinal tight junctions have been hampered by unacceptable side effects induced by the potential absorption enhancers.12 Physiological considerations, such as gastric transit time, dilution,
and interaction with intestinal debris, also inuence peptide absorption across the intestinal
epithelium. Furthermore, peptides absorbed through the hepatic portal vein have to negotiate
with the rst-pass metabolism in the liver.9 |
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| DOI: | 10.1201/b19038-67 |