Impact of Peptide Structure on Colonic Stability and Tissue Permeability.

Most marketed peptide drugs are administered parenterally due to their inherent gastrointestinal (GI) instability and poor permeability across the GI epithelium. Several molecular design techniques, such as cyclisation and D-amino acid (D-AA) substitution, have been proposed to improve oral peptide drug bioavailability. However, very few of these techniques have been translated to the clinic.

A Non-Nutritive Feeding Intervention Alters the Expression of Efflux Transporters in the Gastrointestinal Tract.

Intestinal interactions with nutrients, xenobiotics and endogenous hormones can influence the expression of clinically relevant membrane transporters. These changes in the gastrointestinal (GI) physiology can in turn affect the absorption of numerous drug substrates. Several studies have examined the effect of food on intestinal transporters in male and female humans and animal models.

Quantification of P-Glycoprotein in the Gastrointestinal Tract of Humans and Rodents: Methodology, Gut Region, Sex, and Species Matter.

Intestinal efflux transporters affect the gastrointestinal processing of many drugs but further data on their intestinal expression levels are required. Relative mRNA expression and relative and absolute protein expression data of transporters are commonly measured by real-time polymerase chain reaction (RT-PCR), Western blot and mass spectrometry-based targeted proteomics techniques. All of these methods, however, have their own strengths and limitations, and therefore, validation for optimized quantification methods is needed.

Boosting drug bioavailability in men but not women through the action of an excipient.

Active pharmaceutical ingredients are routinely formulated with a range of excipients in the manufacture of drug products. Excipients are considered to be inert components of the formulations, although recent research has contested its inactive behaviour. This study investigated the effect of the excipient polyethylene glycol 400 (PEG 400) on the oral bioavailability and intestinal permeability of cimetidine in male and female human volunteers.

Effect of Food and an Animal's Sex on P-Glycoprotein Expression and Luminal Fluids in the Gastrointestinal Tract of Wistar Rats.

The rat is one of the most commonly used animal models in pre-clinical studies. Limited information between the sexes and the effect of food consumption on the gastrointestinal (GI) physiology, however, is acknowledged or understood. This study aimed to investigate the potential sex differences and effect of food intake on the intestinal luminal fluid and the efflux membrane transporter P-glycoprotein (P-gp) along the intestinal tract of male and female Wistar rats.

Automated therapy preparation of isoleucine formulations using 3D printing for the treatment of MSUD: First single-centre, prospective, crossover study in patients.

Maple syrup urine disease (MSUD) is a rare metabolic disorder with a worldwide prevalence of 1 in every 185,000 live births. However, certain populations display a significant overexpression of the disorder where incidence is reported to be 1 in every 52,541 new-borns. The first-line therapy for MSUD involves a strict dietary leucine restriction and oral supplementation of isoleucine and valine.

A slippery slope: On the origin, role and physiology of mucus.

The mucosa of the gastrointestinal tract, eyes, nose, lungs, cervix and vagina is lined by epithelium interspersed with mucus-secreting goblet cells, all of which contribute to their unique functions. This mucus provides an integral defence to the epithelium against noxious agents and pathogens. However, it can equally act as a barrier to drugs and delivery systems targeting epithelial passive and active transport mechanisms.