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A review on the strategies for oral delivery of proteins and peptides and their clinical perspectives.

ABSTRACT: In the modern world, a number of therapeutic proteins such as vaccines, antigens, and hormones are being developed utilizing different sophisticated biotechnological techniques like recombinant DNA technology and protein purification. However, the major glitches in the optimal utilization of therapeutic proteins and peptides by the oral route are their extensive hepatic first-pass metabolism, degradation in the gastrointestinal tract (presence of enzymes and pH-dependent factors), large molecular size and poor permeation. These problems can be overcome by adopting techniques such as chemical transformation of protein structures, enzyme inhibitors, mucoadhesive polymers and permeation enhancers. Being invasive, parenteral route is inconvenient for the administration of protein and peptides, several research endeavors have been undertaken to formulate a better delivery system for proteins and peptides with major emphasis on non-invasive routes such as oral, transdermal, vaginal, rectal, pulmonary and intrauterine. This review article emphasizes on the recent advancements made in the delivery of protein and peptides by a non-invasive (peroral) route into the body.

SUBMITTER: Muheem A

PROVIDER: S-EPMC4908063 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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A review on the strategies for oral delivery of proteins and peptides and their clinical perspectives.

Muheem Abdul A Shakeel Faiyaz F Jahangir Mohammad Asadullah MA Anwar Mohammed M Mallick Neha N Jain Gaurav Kumar GK Warsi Musarrat Husain MH Ahmad Farhan Jalees FJ

Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society 20140616 4

In the modern world, a number of therapeutic proteins such as vaccines, antigens, and hormones are being developed utilizing different sophisticated biotechnological techniques like recombinant DNA technology and protein purification. However, the major glitches in the optimal utilization of therapeutic proteins and peptides by the oral route are their extensive hepatic first-pass metabolism, degradation in the gastrointestinal tract (presence of enzymes and pH-dependent factors), large molecula ...[more]

PMID: 27330372

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Project description:The molecular platforms of the innate immune system are essential to recognize pathologic external factors that are crucial to differentiate these danger signals from host motifs. A set of sensors recognizing pathologic factors is present and defined as a membrane-bound family of Toll-like receptors as well as the cytosolic ones including the family of nucleotide-binding domain leucine-rich repeat proteins. In this regard, the inflammasomes have been identified as an innate immune sensor toward pathologic external factors as well as endogenous damage-associated molecular pattern signals transducing from the above-mentioned receptors to gene expressions. Recent research has shown novel findings in inflammasome biology and genetics which lead to the alteration of diagnosis and management in autoinflammatory diseases as well as developing novel treatments, including the examples of nucleotide-binding domain leucine-rich repeat proteins-inflammasomes and pyrin-inflammasomes. The pyrin protein is encoded by the Mediterranean Fever gene on chromosome 16 that acts as a major regulatory component of the inflammasome, and is responsible for familial Mediterranean fever. We have recently examined the whole nucleotide sequence of the Mediterranean Fever gene in Japanese familial Mediterranean fever patients and revealed single nucleotide variants associated with the susceptibility of familial Mediterranean fever from a nation-wide survey by the next-generation sequencing. In a cytokine profile analysis of familial Mediterranean fever patients, we have found that interleukin-6 is considered to be one of the most crucial cytokines in familial Mediterranean fever attack since interleukin-6 had the best performance for distinguishing familial Mediterranean fever in attack from healthy controls or familial Mediterranean fever in remission, and in vitro interleukin-6 production is regulated by microRNAs-204-3p/phosphoinositide 3-kinase g pathway. Accordingly, we have been investigating the efficacy and safety of anti-human interleukin-6 receptor monoclonal antibody, tocilizumab, in patients with familial Mediterranean fever refractory or intolerant to colchicine through an investigator-initiated clinical trial supported by the Japan Agency for Medical Research and Development. Like interleukin-1b, interleukin-18 can be processed by caspase-1 and proteinase-3 to be activated within the inflammasomes. We have also found the importance of interleukin-18 in several autoinflammatory conditions. Recently, the concept of autoinflammation is widely distributed into many common diseases; thus, the attention to a wide spectrum of diseases MEFV gene deeply involved is required.

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A review on the strategies for oral delivery of proteins and peptides and their clinical perspectives.

Publications

A review on the strategies for oral delivery of proteins and peptides and their clinical perspectives.

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