The Oral Delivery of Proteins Using Interpolymer Polyelectrolyte Complexes

Abstract

In spite of the numerous barriers inherent in the oral delivery of therapeutically active proteins, research into the development of functional protein-delivery systems is still intense. The effectiveness of such oral protein-delivery systems depend on their ability to protect the incorporated protein from proteolytic degradation in the GI tract and enhance its intestinal absorption without significantly compromising the bioactivity of the protein. Among these delivery systems are polyelectrolyte complexes (PECs) which are composed of polyelectrolyte polymers complexed with a protein via coulombic and other interactions. This review will focus on the current status of PECs with a particular emphasis on the potential and limitations of multi- or inter-polymer PECs used to facilitate oral protein delivery.

The design of pH-sensitive chitosan-based formulations for gastrointestinal delivery

“…Generally, the pH-responsive properties of chitosanbased polyelectrolyte complexes (PECs) are mainly dependent on the choice of anionic molecule for PEC formation and the charge ratio of two polyelectrolytes [29]. Different anionic molecules possess different charge intensity and the pH of the environmental media modulates ionic interactions between chitosan and anionic molecules and, consequently, PEC properties.…”

Wheat germ agglutinin-functionalised crosslinked polyelectrolyte microparticles for local colon delivery of 5-FU:in vitroefficacy andin vivogastrointestinal distribution

“…Probably, higher zeta potential and the presence of CTS and WGA onto particles surface are acceptable reasons for the observed phenomenon. We could speculate that the slight decrease in the transepithelial electric resistance, but still in range of 200-400 /cm 2 , could be explained by the influence of positive surface charge of the particles as well as the presence of CTS and WGA, resulting in structural reorganisations of tight junction associated proteins (Simon et al, 2007;Pellegrina et al, 2009;Thompson and Ibie, 2011). The calculated apparent permeability coefficients, P app , are reported in Table 1.…”

Oral Delivery of Glucagon-like Peptide-1 and Analogs: Alternatives for Diabetes Control?

“…Moreover, in long-term therapy, the use of enzyme inhibitors can be a problem because it can influence normal absorption of protein nutrients and can also affect the absorption of other peptides/proteins. 37,38,53,55 Thus different approaches should be considered to increase oral bioavailability of GLP-1 and its analogs.…”

“…This variation induces several modifications on peptides that can lead to the loss of their conformation or even to their partial destruction before reaching the intestine. 30,36,37 Another main risk for GLP-1 and its analogs absorption is their rapid degradation by enzymes secreted throughout the GI lumen, like pepsine, pancreatic enzymes, and peptidases and enzymes from the intestinal flora. 30,38,39 Any peptide that survives passage through the chemical and enzymatic degradation must then face the absorption barriers, such as intestinal epithelial cells and the mucus layer.…”