Institute of Pharmaceutical Technology and Buchmann Institute for Molecular Life Sciences, Goethe-University Frankfurt, 60438 Frankfurt am Main, Germany.
Institute of Pharmaceutical Technology and Buchmann Institute for Molecular Life Sciences, Goethe-University Frankfurt, 60438 Frankfurt am Main, Germany.
Int J Pharm. 2023 Nov 5;646:123483. doi: 10.1016/j.ijpharm.2023.123483. Epub 2023 Oct 5.
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.
对于口服给药，纳米载体的物理化学性质是穿透肠上皮的决定性因素。这些性质取决于纳米载体的组成以及自组装过程中的工艺参数。对于大分子药物，对于药物-聚合物相互作用在纳米载体自组装过程中的影响及其对载体性质的影响，仍知之甚少。在这项研究中，研究了药物分子量对纳米载体自组装、纳米载体的物理化学性质以及它们穿过肠上皮的渗透作用的影响。我们的结果表明，药物分子量会影响纳米载体的物理化学性质。此外，由药物分子量决定的纳米载体的物理化学性质决定了它们穿过肠上皮的渗透性能。体外和体内比较研究表明，肠吸收既取决于组织的性质，也取决于载体系统的性质。总之，药物有效载荷的分子量是决定聚合物纳米载体物理化学性质的关键因素，并且与它们的口服吸收密切相关。使用不同的临床前模型来评估纳米载体的肠道渗透，为控制口服生物利用度的关键配方特性提供了新的见解。
