Peptides have been traditionally considered bad candidates for the development of drugs due to some of their pharmacokinetic properties. However, using peptides in drug development is an increasingly popular option. Thanks to recent developments in formulation strategies that solve some of those issues, peptides are carving themselves a spot in the drug development sector.

Sadly, some of these formulation techniques aren’t widely known to researchers all over the world. This makes a compound that combines the advantages of antibodies and small molecules, widely overlooked.

What is a peptide?

In the chemical field, a peptide is a polyamide polymer that contains up to 50 non-canonical amino acids. However, this definition often gets simplified to any short chain of amino acids capable of being artificially synthesized.

Advantages of using peptides in drug development

Peptides have been used in drug development since 1920 when the use of animal-produced Insulin turned upside down diabetes treatment. During the last century, we have identified several advantages to the use of peptides in drug development, as well as in its production method.

When compared with other biological agents, peptides have a longer shelf life and astounding stability at room temperature. Additionally, the absence of a superstructure makes it impossible for them to denaturalize.

Peptides are obtained through chemical synthesis, not depending on cellular activity, as is the case with complete proteins. This makes their production easy and cheap.

Additionally, chemical synthesis allows the introduction of specific modifications to the chain, as well as the creation of cyclic peptides. This increases the amount of versatility at the researcher’s reach.

Custom made peptides

Peptides have limits

Despite the multiple advantages of using peptides in drug development, they also present a series of limitations that researchers should keep in mind.

One of the most considered ones is the problem of absorption in the digestive tract, which is especially limited in peptides. That, and the numerous chemical and enzymatic barriers the peptide must go through in the case of oral intake. The low PH of the gastric juices and even the bacterial flora can cause peptides to degrade.

Another of the pharmacologic limitations peptides face is their limited circulation-half life, due to the presence of proteases in the bloodstream that can reduce them to inactive metabolites. Even stable and hard-to-break peptides are filtered by the kidneys minutes after their absorption.

This short circulation half-life is an obstacle when is time to treat chronic diseases. However, it turns peptides into the ideal substances for emergency situations where the plasma levels can be modified easily.

How can I avoid these limitations?

Since we have been giving peptides more attention as therapeutic agents, the scientific community has developed different strategies that look to overcome the limits of this molecule. Some of these strategies optimize the therapeutic properties of the compound, while others focus on the delivery method, trying to solve the problem without changing the structure of the peptide.

This is the case of chemical modifications, like cyclation or N-metilation, that look to increase the passive permeability of the peptide.

To achieve an active transport, peptides can be conjugated with membrane receptors like lipoprotein receptors or with receptors associated with cellular adhesion.

In the other department, the use of acetylation techniques sharply reduces the activity of proteases and peptides, making so the circulation half-life of the peptide increase considerably. Another way of increasing the proteic stability is adding non-canonical amino acids, that human proteases cannot detect.

The oral intake of peptides tries to bypass some of the barriers it faces with permeability enhancers, which are no more than a group of chemicals that increase the absorption rate by opening pores or changing the fluidity of the membrane.

In other cases, a combination of detoxification and formulation strategies is put in place to get an efficient distribution of the molecule, like in the case of tablets covered in an acid-resistant coat.

Another delivery technology that has been recently developed to improve the absorption of peptides is the use of mucoadhesive polymeric systems. These systems contain polymers like polyacrylic acid, polyethylene oxide or methyl cellulose, that easily adhere to the intestinal epithelium.

The peptide conjugation with big molecules is also used to avoid small and hydrophilic peptides to be filtered by the kidneys. This conjugation technique is often used to produce antibodies that use the peptides as immunogens.

Custom made peptides

Conclusion

Peptides are incredibly potent and selective, making them therapeutic agents with a lot of promise. However, they are limited by their pharmacokinetic properties.

This has brought researchers all over the world to develop a series of strategies to increase their permeability, extend their circulation half-life, increase their stability and resilience to proteases, and make their oral intake a viable option.

Once these techniques are applied, peptides turn into a molecule type full of untapped potential.

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