Pushing the Limits on the Intestinal Crossing of Metal−Organic Frameworks: An Ex Vivo and In Vivo Detailed Study
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AuthorRojas Macías, Sara
American Chemical Society
Metal-Organic FrameworksChitosanIntestinal permeabilityCaenorhabditis elegansBioavailability
ACS Nano 2022, 16, 5830−5838. [https://doi.org/10.1021/acsnano.1c10942]
SponsorshipRamon Areces Foundation project H+MOFs; M-ERA-NET CMOF.cell project - MCIN/AEI PCI2020-111998; European Union NextGenerationEU/PRTR); Comunidad de Madrid; European Regional Development Fund-FEDER 2014-2020-OE REACT-UE 1; MCIN/AEI/FEDER "Una manera de hacer Europa" RTI2018-096273-B-I00 MCIN/AEI PID2019-104228RB-I00 PID2020-112848RB-C21; Generalitat de Catalunya 2017SGR765; "Severo Ochoa" Programme for Centres of Excellence in RD SEV-2015-0496 CEX2019-000917-S; Regional Madrid funding 2017-T2/IND-5149; Juan de la Cierva incorporation JC2019-038894-I; European Union NextGenerationEU/PRTR, Multifunctional Metallodrugs in Diagnosis and Therapy Network (MICIU) RED2018-102471-T
Biocompatible nanoscaled metal−organic frameworks (nanoMOFs) have been widely studied as drug delivery systems (DDSs), through different administration routes, with rare examples in the convenient and commonly used oral administration. So far, the main objective of nanoMOFs as oral DDSs was to increase the bioavailability of the cargo, without considering the MOF intestinal crossing with potential advantages (e.g., increasing drug availability, direct transport to systemic circulation). Thus, we propose to address the direct quantification and visualization of MOFs’ intestinal bypass. For that purpose, we select the microporous Fe-based nanoMOF, MIL- 127, exhibiting interesting properties as a nanocarrier (great biocompatibility, large porosity accessible to different drugs, green and multigram scale synthesis, outstanding stability along the gastrointestinal tract). Additionally, the outer surface of MIL-127 was engineered with the biopolymer chitosan (CS@MIL-127) to improve the nanoMOF intestinal permeation. The biocompatibility and intestinal crossing of nanoMOFs is confirmed using a simple and relevant in vivo model, Caenorhabditis elegans; these worms are able to ingest enormous amounts of nanoMOFs (up to 35 g per kg of body weight). Finally, an ex vivo intestinal model (rat) is used to further support the nanoMOFs’ bypass across the intestinal barrier, demonstrating a fast crossing (only 2 h). To the best of our knowledge, this report on the intestinal crossing of intact nanoMOFs sheds light on the safe and efficient application of MOFs as oral DDSs.