Advanced Approaches of Bioactive Peptide Molecules and Protein Drug Delivery Systems

Abstract

Despite the fact that protein and peptide therapeutics are widely employed in the treatment of various diseases, their delivery is posing an unembellished challenge to the scientists. It was discovered that delivery of these therapeutic systems through oral route is easy with high patient compliance. However, proteolytic degradation and absorption through the mucosal epithelium are the barriers in this route. These issues can be minimized by the use of enzyme inhibitors, absorption enhancers, different carrier systems or either by direct modification. In the process of investigation, it was found that transdermal route is not posing any challenges of enzymatic degradation, but, still absorption is the limitation as the outer layer of skin acts as a barrier. To suppress the effect of the barrier and increase the rate of the absorption, various advanced technologies were developed, namely, microneedle technology, iontophoresis, electroporation, sonophoresis and biochemical enhancement. Indeed, even these molecules are targeted to the cells with the use of cell-penetrating peptides. In this review, delivery of the peptide and protein therapeutics using oral, transdermal and other routes is discussed in detail.

Bioactive Peptides: From Basic Research to Clinical Trials and Commercialization

“…Bioactive peptides are likely susceptible to degradation either during digestion in the gastrointestinal tract or during absorption in small intestinal epithelial cells. 110 Even though some peptides can exert their bioactivity locally, for example, by regulating nutrient absorption or gut mobility, most bioactive peptides are expected to be transported across the human intestinal barrier in an intact or active form into the bloodstream and then exert their bioactivity after reaching the target sites. 111 Only a few known peptides escape degradation and have been found intact in the blood circulation, including collagen peptides, 112 ACE inhibiting peptides, 113 and a dipeptide VY.…”

“…Second, most bioactive peptides have low bioavailability. Bioactive peptides are likely susceptible to degradation either during digestion in the gastrointestinal tract or during absorption in small intestinal epithelial cells . Even though some peptides can exert their bioactivity locally, for example, by regulating nutrient absorption or gut mobility, most bioactive peptides are expected to be transported across the human intestinal barrier in an intact or active form into the bloodstream and then exert their bioactivity after reaching the target sites .…”

“…Peptides entering blood circulation are reported to have a short half-life (between 15 min and 2 h). To ensure the effective delivery of bioactive peptides to the sites of action, there is a need to develop new strategies to protect the stability and the native structure of the peptides, including encapsulation and peptide mimetics, to name a few. , Thus, future research should focus on the bioavailability and the transportation of bioactive peptides to their targeted sites.…”

De novo fabrication of oral insulin-loaded chitosan/dextrin/pectin nanospheres and their antidiabetic efficacy in streptozotocin-induced diabetic rats

“…Dextrin has also been shown to decrease triglyceride levels and reduce the glycemic index of meals, which helps to maintain healthy blood sugar levels [12]. Furthermore, dextran can protect insulin against the GIT proteases via its chemical linkage to insulin [13].…”

Recent Progress of Rational Modified Nanocarriers for Cytosolic Protein Delivery

“…In recent years, specific proteins such as adrenocorticotrophic hormone, monoclonal antibodies, enzymes, cytokines, and peptides were developed as therapeutic agents for conditions such as anti-inflammation, cancer metastasis, indigestion diseases, and viral infections [ 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 ]. Notably, five out of the top ten best-selling drugs in 2021 were protein antibodies, according to statistics on top companies and drug sales [ 19 ]. Consequently, the demand for protein drugs steadily increased in the pharmaceutical market.…”