Application of Permeation Enhancers in Oral Delivery of Macromolecules: An Update

Abstract

The application of permeation enhancers (PEs) to improve transport of poorly absorbed active pharmaceutical ingredients across the intestinal epithelium is a widely tested approach. Several hundred compounds have been shown to alter the epithelial barrier, and although the research emphasis has broadened to encompass a role for nanoparticle approaches, PEs represent a key constituent of conventional oral formulations that have progressed to clinical testing. In this review, we highlight promising PEs in early development, summarize the current state of the art, and highlight challenges to the translation of PE-based delivery systems into safe and effective oral dosage forms for patients.

Influence of Bile Composition on Membrane Incorporation of Transient Permeability Enhancers

“…One approach to enhance the absorption of poorly permeable drugs through the intestinal epithelium is coadministration with transient permeability enhancers (PEs). 1 − 3 A number of formulations for oral peptide delivery based on transient PEs went into clinical trials. 4 − 9 Among the most efficient transient PEs for poorly permeable molecules are the medium-chain fatty acids (MCFAs) such as sodium caprate, caprylate, and MCFA-based enhancers such as salcaprozate sodium (SNAC; a derivative of caprylate).…”

Recent Advances in Encapsulation, Protection, and Oral Delivery of Bioactive Proteins and Peptides using Colloidal Systems

“…Moreover, efflux inhibitors are typically less effective for BPPs than for small hydrophobic molecules (with the exception of the peptide cyclosporine). [48,50,51]. Some CDSs naturally contain components (such as surfactants or medium chain fatty acids) that can increase the permeability of cell membranes, which may also be useful for increasing BPP absorption [50].…”

“…Incorporating protease inhibitors in CDS can help to reduce the hydrolysis of BPPs in the gut (but can also have adverse effects on normal digestion processes), whereas coating colloidal particles with mucoadhesive materials can increase their retention in the small intestine, thereby allowing more time for absorption to occur [11]. Because the absorption of many BPPs is inherently low, special strategies have to be developed to increase it e.g., permeation enhancers, mucoadhesive materials, or colloidal carriers can be utilized [11,48]. Permeation enhancers can increase the absorption of substances in the GIT by temporarily disrupting the intestinal barrier, by increasing membrane fluidity, or by opening the connections (tight junctions) separating the epithelium cells [11,49].…”

“…Other types of permeation enhancer are also used commercially to increase the absorption of BPPs within the human gut. For example, semaglutide (Rybelsus ® , Novo-Nordisk, Plainsboro Township, NJ, USA) is an orally administered drug designed to treat Type 2 diabetes, which contains a permeation enhancer (salcaprozate sodium) to increase the amount of a GLP-1 receptor agonist absorbed by the body [48,50,51]. Some CDSs naturally contain components (such as surfactants or medium chain fatty acids) that can increase the permeability of cell membranes, which may also be useful for increasing BPP absorption [50].…”

Aloe vera gel and whole leaf extract: functional and versatile excipients for drug delivery?

“…Unfortunately, the oral route of drug administration is plagued with low bioavailability and poor absorption of protein and peptide drugs, which can be attributed to enzymatic degradation and a large molecular structure of these drugs that causes low membrane permeability [6]. One approach that has been extensively investigated to overcome the low bioavailability of drugs after oral drug administration includes the utilization of chemical permeation enhancers [7].…”