Protein and peptide drug delivery: Oral approaches

Abstract

Till recent, injections remained the most common means for administering therapeutic proteins and peptides because of their poor oral bioavailability. However, oral route would be preferred to any other route because of its high levels of patient acceptance and long term compliance, which increases the therapeutic value of the drug. Designing and formulating a polypeptide drug delivery through the gastro intestinal tract has been a persistent challenge because of their unfavorable physicochemical properties, which includes enzymatic degradation, poor membrane permeability and large molecular size. The main challenge is to improve the oral bioavailability from less than 1% to at least 30-50%. Consequently, efforts have intensified over the past few decades, where every oral dosage form used for the conventional small molecule drugs has been used to explore oral protein and peptide delivery. Various strategies currently under investigation include chemical modification, formulation vehicles and use of enzyme inhibitors, absorption enhancers and mucoadhesive polymers. This review summarizes different pharmaceutical approaches which overcome various physiological barriers that help to improve oral bioavailability that ultimately achieve formulation goals for oral delivery.

Electrodeposited conductive polymers for controlled drug release: polypyrrole

“…Through this route, the drugs can break down by the acid environment of the stomach and by the intestine enzymes. Drug absorption in the digestive system is difficult and most macromolecules cannot be absorbed, which limits the effectiveness of the drug before reaching its target location [27][28][29].…”

Antihypertensive Properties of Plant Protein Derived Peptides

“…The improvement of limited absorption and stability of peptides has been a goal when evaluating their effectiveness. For example, some carriers interact with the peptide molecule to create an insoluble entity at low pH, which later dissolves and facilitates intestinal uptake, by enhancing peptide transport over the non-polar biological membrane [169]. Bioavailability of bioactive tri-peptides (Val-Pro-Pro, Ile-Pro-Pro, Leu-Pro-Pro) was improved by administering them with a meal containing fibre, as compared to a meal containing no fibre.…”

“…High methylated citrus pectin was used as a fibre [170]. Among drug delivery systems, emulsions have been used to enhance oral bioavailability or promoting absorption through mucosal surfaces of peptides and proteins [169]. Individually, various components of emulsions have been considered as candidates for improving bioavailability of peptides.…”

Lactic Fermentation and Bioactive Peptides

“…For example, some carriers interact with the peptide molecule to create an insoluble entity at low pH which later dissolves and facilitates intestinal uptake, by enhancing peptide transport over the non-polar biological membrane [118]. Bioavailability of bioactive tripeptides (VPP, IPP, LPP) was improved by administering them with a meal containing fiber, as compared to a meal containing no fiber.…”

“…In this case, phospholipids were identified as responsible for enhancing the antihypertensive effect, particularly phosphatidylcholine, that could improve intestinal absorption or by protecting ovokinin of peptidases. Among drug delivery systems, emulsions have been used to enhance oral bioavailability or promoting absorption through mucosal surfaces of peptides and proteins [118]. Individually, various components of emulsions have been considered as candidates for improving bioavailability of peptides.…”