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.

Chemically Precise Glycoengineering Improves Human Insulin

“…If insulin is to be absorbed in the small intestine, it must survive the stomach and conditions in the small intestine. 13 Fortunately, a number of pH sensitive materials have been recently developed that are capable of protecting insulin from the environment of the stomach and selectively releasing insulin when encountering the neutral pH conditions of the small intestine. 14 Currently, this leaves insulin’s low absorption in the small intestine (Figure 1B) as the major barrier standing in the way of developing oral insulin.…”

Functionalized Polymers for Enhance Oral Bioavailability of Sensitive Molecules

“…Some of the most exposed problems in several reviews are related to permeation [5,13,20,110]. The physicochemical properties of sensitive molecules and conditions of absorption of FP systems have also limited their function [111,112].…”

“…In addition, other results have showed that FP nano carriers can reduce the transepithelial resistance [60]; therefore, their potential use for clinical applications is still uncertain [20]. Consequently, some FP systems still cannot be used in oral formats due to their low efficacy.…”

“…Figure 1 shows the most studied FP systems for sensitive molecules delivery. Several FP are used as base materials to fulfill the purpose; such as, polysaccharides (chitosan, starch and cellulose derivatives); proteins (gelatin, soy, casein and whey), poly(acrylic acid) (PAAc), glycerol, PEG and various gums such as guar, xanthan, PVP and PVA [19,20]. Hydrophilic polymers like poly(vinyl pyrrolidone) (PVP) or PEG provided stability and solubility properties to sensitive molecules, since they act as solubility enhancement.…”

What is the Future of Noninvasive Routes for protein- and peptide-based drugs?

“…A successful oral protein formulation in the future can also utilize the smart polymeric nanoparticles which can protect and target the proteins to the specific site and release when required [6,7].…”