PLGA-PEG-Mal used in research on intestinal permeation for oral bioavailability research

 

Oral bioavailability references the ability of a drug taken orally (either as a tablet or as a drinkable liquid) to be successfully taken into the bloodstream and circulate throughout the patient’s body. One classic example of oral bioavailability is acetylsalicylic acid (Aspirin) which has roughly 50% bioavailability. In the case of aspirin, the drug is readily available and cheaply manufactured so the incredibly unimaginative and yet wildly effective manner of dealing with 50% bioavailability was to double the dose given to the patient, knowing that about 50% of the drug will simply be lost without any benefit. Not all bioavailability problems can be addressed in such a simplistic manner as some molecules have little to no bioavailability or require carefully controlled dosing. In this case, understanding the exact bioavailability is critical and one of the most important rate-limiting steps of bioavailability is the ability for drugs to cross the intestinal mucosa layer into the blood stream. The small intestine is, metaphorically, the ‘Suez Canal’ of the human body and understanding uptake across the intestine is critical to bioavailability. Recently, researchers at University of Porto (Portugal), University of Oslo (Norway), Harvard Medical School, Massachusetts Institute of Technology, and Universitário de Ciências da Saúde (Portugal) used PLGA-PEG-Mal (AI110) from PolySciTech (www.polyscitech.com) to create particles decorated with neonatal Fc receptor to test their intestinal permeation model of specially prepared porcine mucosa. This research holds promise to improve oral delivery of medicines. Read more: Azevedo, Cláudia, Jan Terje Andersen, Giovanni Traverso, and Bruno Sarmento. "The potential of porcine ex vivo platform for intestinal permeability screening of FcRn-targeted drugs." European Journal of Pharmaceutics and Biopharmaceutics (2021). https://www.sciencedirect.com/science/article/abs/pii/S0939641121000746

“Highlights: FcRn is expressed across the gastrointestinal tract. FcRn expression in ex vivo porcine tissue is maintained up to 7 days in culture. Free KP present higher permeability in porcine ex vivo platform. The porcine ex vivo platform was revealed to be a potential model for the screening of FcRn-targeted oral drug formulations. Abstract: Conventionally, the intestinal permeability of drugs is evaluated using cell monolayer models that lack morphological, physiological and architectural features, as well as realistic neonatal Fc receptor (FcRn) expression. In addition, it is time-consuming, expensive and excessive to use a large number of mice for large-scale screening of FcRn-targeted candidates. For preclinical validation, it is critical to use suitable models that mimic the human intestine; the porcine ex vivo model is widely used for intestinal permeability studies, due to its physiological and anatomical similarities to humans. This study intended to analyze the potential to measure the intestinal permeability of FcRn-targeted substances using a porcine ex vivo platform, which is able to analyze 96 samples at the same time. In addition, the platform allows the screening of FcRn-targeting substances for transmucosal delivery, taking into consideration (cross-species) receptor-ligand binding kinetics. After analyzing the morphology of the porcine tissue, the FcRn expression across the gastrointestinal tract was verified. By studying the stomach, duodenum and jejunum, it was demonstrated that FcRn expression is maintained for up to 7 days. When evaluating the duodenum permeability of free engineered human albumin variants, it was shown that the variant with the mutation K573P (KP) is more efficiently transported. Given this, the porcine ex vivo platform was revealed to be a potential model for the screening of FcRn-targeted oral drug formulations.”