RT Journal Article
T1 Nanoassemblies for oral protein delivery — The case of monoclonals for inflammatory bowel disease
A1 López Estévez, Ana M.
A1 Portela, María G.
A1 Piñeiro Alonso, Laura
A1 Castillo González, Raquel
A1 Sancho Temiño, Lucía
A1 Gómez Lado, Noemí
A1 Codesido, Jessica
A1 García Otero, Xurxo
A1 Medel, María
A1 Vicent, María J.
A1 Castellanos, Milagros
A1 Aguiar, Pablo
A1 Fernández Messina, Lola María
A1 Fernández Aceñero, María Jesús
A1 Cruz Adalia, Aranzazu
A1 Alonso, María José
AB 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.
PB Elsevier
SN 0168-3659
YR 2026
FD 2026-01
LK https://hdl.handle.net/20.500.14352/132316
UL https://hdl.handle.net/20.500.14352/132316
LA eng
NO 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
NO This work was supported by the government of Xunta de Galicia (Competitive Reference Groups, Consellería de Educación e Ordenación Universitaria, Xunta de Galicia, Ref: ED431C 2021/17); and by Xunta de Galicia (Centro singular de Investigación de Galicia Accreditation 2019-2022) and the European Union (European Regional Development Fund – ERDF, Ref: ED431G 2019/02). M.G.P. is a recipient of a predoctoral grant (ED481A - 2024-203) from Xunta de Galicia. L.P.A acknowledges a grant (ED481A 2022/237) from Xunta de Galicia “Axudas de apoio á etapa predoutoral 2021”. R.C.-G. is a recipient of a Juan de la Cierva grant (FJC2021-047282-I) from the Ministerio de Ciencia e Innovación and L.S.-T. is a recipient of a FPU grant (FPU22/02155) from the “Ministerio de Educación y Formación Profesional”. A.C.-A. was funded by the grants PID2021-122780OB-I00 and CNS2022-135365 from the “Ministerio de Ciencia e Innovación”.
NO Xunta de Galicia
NO Ministerio de Ciencia e Innovación (España)
NO European Commission
DS Docta Complutense
RD 30 jul 2026