Pushing the Limits on the Intestinal Crossing of Metal–Organic Frameworks: An <i>Ex Vivo</i> and <i>In Vivo</i> Detailed Study

  1. Rojas, Sara 3
  2. Hidalgo, Tania 3
  3. Luo, Zhongrui 2
  4. Ávila, David 1
  5. Laromaine, Anna 2
  6. Horcajada, Patricia 3
  1. 1 Department of Inorganic Chemistry, Chemical Sciences Faculty, Complutense University of Madrid, 28040 Madrid, Spain
  2. 2 Institut de Ciència de Materials de Barcelona (ICMAB-CSIC), Campus UAB, 08193 Bellaterra, Spain
  3. 3 Advanced Porous Materials Unit (APMU), IMDEA Energy Institute, Av. Ramón de la Sagra 3, 28935 Móstoles-Madrid, Spain
Mostrar afiliaciones +
Revista:
ACS Nano

ISSN: 1936-0851,  1936-086X

Año de publicación: 2022

Volumen: 16

Número: 4

Páginas: 5830-5838

Tipo: Artículo

DOI: 10.1021/ACSNANO.1C10942 GOOGLE SCHOLAR lock_openAcceso abierto editor

Otras publicaciones en: ACS Nano

Resumen

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

€ Ver financiación

Información de financiación

Financiadores

Referencias bibliográficas

  • 10.1002/anie.200601878
  • 10.1038/46248
  • 10.1016/j.ccr.2020.213651
  • 10.1021/acsami.0c07356
  • 10.3390/pharmaceutics12050437
  • 10.1039/C6TB01652A
  • 10.1021/acsami.8b20222
  • 10.3390/nano10122296
  • 10.1021/acs.molpharmaceut.7b00168
  • 10.1002/adfm.201904828
  • 10.1021/acsami.0c04303
  • 10.1039/D0TB02804E
  • 10.3389/fphar.2020.00524
  • McGhee J. D., (2007), WormBook
  • 10.1016/j.actbio.2017.01.080
  • 10.1039/C2CY00376G
  • 10.1039/C3TB20832J
  • 10.1021/acsomega.8b00185
  • 10.1021/cm400798p
  • 10.1039/C5CE01864A
  • Patel J., (2015), Biointeractions of Nanomaterials, pp. 286
  • 10.1016/j.ijbiomac.2020.03.148
  • 10.1016/j.jddst.2020.101813
  • 10.1007/978-3-319-16104-4_24
  • 10.1039/C5CE01864A
  • 10.1038/srep43099
  • 10.1016/j.reactfunctpolym.2019.104459
  • 10.1021/cr2000916
  • 10.1021/acsnano.0c08913
  • 10.3389/fmicb.2018.03158
  • 10.3390/ijms19010092
  • 10.1016/S0016-5085(89)80072-1
  • 10.1016/j.cis.2015.02.001
  • 10.1002/smll.201801900
  • 10.1038/srep07925
  • 10.1002/adhm.201400755
  • Hall D. H., (2008), C. elegans Atlas
  • 10.1021/jacs.8b04435
  • 10.1021/acsami.9b06472
  • 10.1152/ajpgi.90649.2008
  • 10.1074/jbc.275.2.1023
  • 10.1152/ajpgi.00348.2013
  • 10.1002/bdd.751
  • 10.1016/j.addr.2008.09.012
  • 10.1016/j.jconrel.2012.08.005