The emerging field of peptide and protein therapeutics is responsible for a new therapeutic era. Peptides are attractive therapeutic molecules due to their high specificity and potency. Peptides biodegrade into nontoxic or low toxicity metabolites, with minimal potential for drug–drug interactions and low immunogenicity compared to larger proteins. These advantages are reflected in a regulatory approval rate of more than 20% probability, which is double that of small molecules (1). The average number of new candidates entering clinical evaluation every year has steadily increased from 1.2 per year in the 1970s to 4.6 per year in the 1980s, 9.7 per year in the 1990s, and 16.8 per year in the 2000s (2).
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Peptides were not favored as drug candidates because of their physicochemical characteristics and the necessity for expensive and complicated manufacturing processes. Peptides often have short half-lives (of less than 20 minutes), thereby making chronic administration problematic and costly. Two major technological advances contributed to the industrial acceptability of peptide-drug candidates:
- Advances in genetic engineering, recombinant technologies, and solid-phase peptide synthesis overcoming the problems of high cost of manufacture as well as stability issues of peptide molecules
- Advancements of polymer technologies allowing controlled long-acting release formulations of peptides encapsulated in biodegradable polymers such as the gonadotrophin-releasing hormone (e.g., goserelin acetate [Zoladex, AstraZeneca]).
Today, the most important drawback in translating peptides into clinically useful therapies is the lack of adequate oral bioavailability. As the preferred route of administration for medicines is the oral route, and given the lack of patient compliance with therapeutics that require chronic self-intravenous administration, the pharmaceutical industry originally opted to focus its efforts on the development of oral alternatives for peptide-based drugs.
Due to the increasing cost of R&D and the decreasing number of approved drugs, new alternative approaches are needed to boost the productivity of the pharmaceutical industry (3). Parenteral administration of peptides is usually painful, and requires sterile manufacturing or aseptic processing of thermally unstable biomacromolecules. Technologies that enable the delivery of biologicals across mucosal barriers such as the gastrointestinal tract (GIT), the nasal mucosa, and the blood-brain barrier (BBB), therefore, offer potential for the development of effective and safe noninvasive biologicals, and can enhance the commercial success of peptide therapeutics.
Aikaterini Lalatsa, PhD