2026-07-30T06:03:18Zhttps://docta.ucm.es/rest/oai/request

oai:docta.ucm.es:20.500.14352/1323162026-02-14T01:13:46Zcom_20.500.14352_14col_20.500.14352_15

Nanoassemblies for oral protein delivery — The case of monoclonals for inflammatory bowel disease López Estévez, Ana M. Portela, María G. Piñeiro Alonso, Laura Castillo González, Raquel Sancho Temiño, Lucía Gómez Lado, Noemí Codesido, Jessica García Otero, Xurxo Medel, María Vicent, María J. Castellanos, Milagros Aguiar, Pablo Fernández Messina, Lola María Fernández Aceñero, María Jesús Cruz Adalia, Aranzazu Alonso, María José Biological drugs such as monoclonal antibodies (mAbs) or peptides are the preferred therapeutic approach for the treatment of chronic diseases such as inflammatory bowel disease (IBD) or diabetes. Unfortunately, the necessity of their parenteral administration and poor access to their targets have limited their full exploitation. Nanotechnology has been explored for the oral administration of biologicals, however, the nanocarriers reported so far have shown limited translational value. The objective of this work has been to design a new nanocarrier for the oral administration of therapeutic proteins with a translational potential. We chose as cargos, insulin and two clinically relevant mAbs, Bevacizumab (BVZ, anti-VEGF-A mAb) and Adalimumab (anti-Tumor Necrosis Factor (TNF) mAb). These macromolecules were assembled with amphiphilic biodegradable polymers, either positively charged (based on octaarginine-lauric r8C12) or negatively charged (polyglutamic acid derivatized with myristic acid, PGAC14) with the intention to assess their potential to facilitate the targeted delivery of the selected proteins. After a screening of a library of compositions, nanoformulations named as nanoassemblies (NAs) exhibiting singular features were selected, namely (i) a ultra-small and unimodal size of 50 nm and negative to neutral surface charge, (ii) a high drug loading capacity (>10 %, w/w), (iii) the ability to protect the cargo in simulated GI fluids, and (iv) the capacity to interact with the intestinal epithelium. In vivo PET/MRI biodistribution profile indicates that NAs consisting of BVZ-r8C12 are significantly retained in the colon as compared to free BVZ. The biodistribution analysis in a rat colitis model revealed that the inflamed conditions enhanced significantly the retention pattern of the NAs. On the other hand, a specific prototype containing anti-TNF (PEGylated NAs of anti-TNF mAb and PGAC14) were able to reduce the production of pro-inflammatory cytokines and decrease the colonic inflammation. Briefly, we present a new oral protein delivery platform and show the potential of specific prototypes for treating local inflammation in intestinal tissues. We also realize that to assess their potential further we need to fully understand their mechanism of action. 2026-02-13T12:31:34Z 2026-02-13T12:31:34Z 2026-02-13T12:31:34Z 2026-01 journal article https://hdl.handle.net/20.500.14352/132316 0168-3659 10.1016/j.jconrel.2025.114455 1873-4995 eng info:eu-repo/grantAgreement/Xunta de Galicia//ED431C 2021%2F17/ info:eu-repo/grantAgreement/Xunta de Galicia//ED431G 2019%2F02/ info:eu-repo/grantAgreement/MICINN//PID2021-122780OB-I00/ info:eu-repo/grantAgreement/MICINN//CNS2022-135365/ López-Estévez, A. M., Portela, M. G., Piñeiro-Alonso, L., Castillo-González, R., Sancho-Temiño, L., Gómez-Lado, N., Codesido, J., García-Otero, X., Medel, M., Vicent, M. J., Castellanos, M., Aguiar, P., Fernández-Messina, L., Fernández-Aceñero, M. J., Cruz-Adalia, A., & Alonso, M. J. (2026). Nanoassemblies for oral protein delivery—The case of monoclonals for inflammatory bowel disease. Journal of Controlled Release, 389, 114455. https://doi.org/10.1016/j.jconrel.2025.114455 http://creativecommons.org/licenses/by-nc-nd/4.0/ open access Attribution-NonCommercial-NoDerivatives 4.0 International Elsevier