Proteins and peptides, which are known as the “building blocks of life,” have become a significant base for treating a wide range of disorders. Over the previous three decades, and more significantly, the past decade, there has been a rapid expansion in therapeutic proteins, with a notable increase in the quantity of protein-based medications that are now accessible on the market.
Peptides have an advantage over small-molecule medications in that they are incredibly selective. As a result, they exhibit fewer off-target responses owing to the large number of interactions they have with their target. This is in contrast to the situation with small-molecule therapies. In addition, most peptides are typically well tolerated, have lower overall systemic toxicity, and usually have minimal immunogenicity.
Insulin, calcitonin, cyclosporine, leucine encephalin, HIV protease, and a wide variety of other peptides have all been the subject of research by pharmaceutical companies over several years.
The oral administration of biologics such as peptides continues to be a complex problem. Peptides tend to be hydrophilic, which is one source of difficulty. Due to the poor water solubility of these molecules, it isn’t easy to achieve the levels of absorption necessary to provide any desired therapeutic effect.
Peptides are prone to modification and degradation at the hands of digestive enzymes in the gastrointestinal (GI) tract. In addition, peptides tend to display short half-lives due to the quick clearance of proteolytic enzymes in the liver and other organs. Peptides must first migrate past the thick mucosal layer that protects the GI tract and then pass the tight junction gap in the epithelium to reach circulation. This is one method by which peptides may enter the body. The vast majority of hydrophilic molecules are unable to complete the journey. Because of this, complicated post-translational changes are often required to ensure good bioactivity and resistance characteristics, which results in higher production costs.
Getting around the problems associated with oral peptide administration
The use of excipients intended to impede enzyme degradation and promote permeability is one of the most common tactics for overcoming the problems of oral peptides for sale. This strategy is one of the most often employed strategies. Methods such as encapsulation and applying protective layers are also often used.
The use of mucoadhesive polymeric systems, specifically designed emulsions, polysaccharides, inorganic nanoparticles, microspheres, and liposomes, as well as derivatization with polyethylene glycol, hybridization with cell-permeating peptides, and the conversion of peptides into prodrugs, is also receiving a significant amount of attention.
Because lipids have excellent biocompatibility and the ability to migrate across the intestinal mucosal barrier, solutions based on lipids are very useful. In addition to liposomes, researchers are looking at multi-emulsions, self-emulsifying drug delivery systems (SEDDS), self-nano emulsifying drug delivery systems (SNEDDS), and self-emulsifying solid lipid particles (SLPs).
Compared to traditional organic small molecules, therapeutic peptides tend to have a lower incidence of unwanted side effects due to their exact targets on cell surfaces, enhanced potency and efficiency, and propensity to demonstrate less unfavorable responses. Despite this, the vast majority of the agents that are now available are designed to be administered through injection. Why is it the case? Few businesses are willing to accept the financial and scientific risk of developing a novel peptide and a non-injected method of administration in the same formulation due to expensive investments in the 1990s that did not provide desirable returns. This is a direct result of such investments. Pharmaceutical companies are far more likely to think about developing non-injected formulations for an already known peptide or protein solely on the market. Because of this strategy, scientists working on oral peptide formulation can only deal with a small number of peptides already on the market. These peptides were first developed for injection by medicinal chemists.