RT Journal Article
T1 Bioinspired orthogonal-shaped protein–biometal nanocrystals enable oral protein absorption
A1 Durán Lobato, Matilde
A1 Tovar Carro, Sulay A.
A1 Cuñarro, Juan
A1 Chenlo Miranda, Miguel Ángel
A1 Álvarez Villamarín, María Clara
A1 Alonso Fernández, María José
K1 Peptide delivery
K1 Protein delivery
K1 Oral delivery
K1 Transmucosal
K1 Biologicals
K1 Nanocomplexes
AB With the growing number of marketed biological drugs, the development of technological strategies for their oral systemic absorption, becomes increasingly important. The harsh gastrointestinal environment and low permeability of the intestinal epithelium, represent a huge challenge for their systemic delivery. Herein, bioinspired in the physiological insulin-Zn interaction, the design of orthogonal-shaped protein-biometal hybrid nanocrystals, further enveloped by a bilayer of functional biomaterials, is reported. The nanocrystals exhibited a size of 80 nm, a neutral surface charge and a high insulin loading. In vitro studies showed the capacity of the nanocomplexes to control the release of the associated insulin, while preserving its stability. In vivo evaluation showed sustained blood glucose reductions in both healthy and diabetic rats (up to 40 % and 80 %, respectively), while chronic immunotoxicity studies in mice indicated no toxicity effect. Preliminary efficacy studies in healthy awake pigs following oral capsule administration showed over 20 % absolute bioavailability.
PB Elsevier
SN 0168-3659
YR 2024
FD 2024-11-17
LK https://hdl.handle.net/10347/42376
UL https://hdl.handle.net/10347/42376
LA eng
NO Matilde Durán-Lobato, Sulay Tovar, Juan Cuñarro, Rocío Ramos-Membrive, Iván Peñuelas, Ilaria Marigo, Federico Benetti, Miguel Chenlo, Clara V. Álvarez, Vashegyi Ildikó, Rudolf Urbanics, János Szebeni, María José Alonso, Bioinspired orthogonal-shaped protein–biometal nanocrystals enable oral protein absorption, Journal of Controlled Release, Volume 377, 2025, Pages 17-36, ISSN 0168-3659, https://doi.org/10.1016/j.jconrel.2024.11.016
NO This work was supported by the European TRANS-INT Consortium, which received funding from the European Union’s Seventh Framework Programme for research, technological development and demonstration under grant agreement NO. 281035. M. Duran-Lobato' acknowledges a postdoctoral fellowship (Contrato de Acceso al Sistema Espanol ˜ de Ciencia, Tecnología e Innovacion ´ (grant number USE-19533-Y)) granted by “VI Plan Propio” from the University of Seville.
DS Minerva
RD 23 abr 2026