Abstract
For oral delivery, the physicochemical properties of nanocarriers are decisive factors for permeation through the intestinal epithelium. These properties are determined by the composition of the nanocarriers as well as by the process parameters during their self-assembly. For macromolecular drugs, there is still little understanding of the drug-polymer interactions during nanocarrier self-assembly and the effects on carrier properties. In this study, the effect of drug molecular weight on nanocarrier self-assembly, physicochemical properties of nanocarriers as well as their permeation across the intestinal epithelium was investigated. Our results show that the drug molecular weight impacts the physicochemical properties of nanocarriers. Further, the physicochemical properties of the nanocarriers, governed by the molecular weight of the drug, determine their permeation properties across the intestinal epithelium. Comparative in vitro and ex vivo studies revealed that intestinal absorption is dependent on both, the properties of the tissue as well as properties of the carrier system. In conclusion, the molecular weight of drug payload is a key factor determining the physiochemical properties of polymeric nanocarriers and is closely linked to their oral absorption. Using different preclinical models to evaluate intestinal permeation of nanocarriers allows for novel insights into key formulation properties governing oral bioavailability.
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