Bioinspired orthogonal-shaped protein-biometal nanocrystals enable oral protein absorption.

Autor: Durán-Lobato M; Center for Research in Molecular Medicine & Chronic Diseases (CIMUS), University of Santiago de Compostela, Campus Vida, 15782 Santiago de Compostela, Spain; Health Research Institute of Santiago de Compostela (IDIS), University of Santiago de Compostela, Campus Vida, 15782 Santiago de Compostela, Spain; Department of Pharmacology, Pharmaceutics and Pharmaceutical Technology, School of Pharmacy, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain; Departamento de Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Universidad de Sevilla, Prof. García González, 2, 41012 Seville, Spain., Tovar S; Center for Research in Molecular Medicine & Chronic Diseases (CIMUS), University of Santiago de Compostela, Campus Vida, 15782 Santiago de Compostela, Spain; Health Research Institute of Santiago de Compostela (IDIS), University of Santiago de Compostela, Campus Vida, 15782 Santiago de Compostela, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Madrid, Spain., Cuñarro J; Center for Research in Molecular Medicine & Chronic Diseases (CIMUS), University of Santiago de Compostela, Campus Vida, 15782 Santiago de Compostela, Spain; Health Research Institute of Santiago de Compostela (IDIS), University of Santiago de Compostela, Campus Vida, 15782 Santiago de Compostela, Spain., Ramos-Membrive R; Radiopharmacy Unit, Department of Nuclear Medicine, Clínica Universidad de Navarra, Instituto de Investigación Sanitaria de Navarra (IdiSNA), Av. Pío XII 36, 31008 Pamplona, Spain; Translational Molecular Imaging Unit, Department of Nuclear Medicine, Clínica Universidad de Navarra, Instituto de Investigación Sanitaria de Navarra (IdiSNA), Av. Pío XII 36, 31008 Pamplona, Spain., Peñuelas I; Radiopharmacy Unit, Department of Nuclear Medicine, Clínica Universidad de Navarra, Instituto de Investigación Sanitaria de Navarra (IdiSNA), Av. Pío XII 36, 31008 Pamplona, Spain; Translational Molecular Imaging Unit, Department of Nuclear Medicine, Clínica Universidad de Navarra, Instituto de Investigación Sanitaria de Navarra (IdiSNA), Av. Pío XII 36, 31008 Pamplona, Spain., Marigo I; Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy; Veneto Institute of Oncology IOV-IRCCS, Padova, Italy., Benetti F; ECSIN-European Center for the Sustainable Impact of Nanotechnology, ECAMRICERT SRL, Padova, Italy., Chenlo M; Neoplasia & Endocrine Differentiation P0L5, Centre for research in Molecular Medicine and Chronic Disease (CIMUS), Av Barcelona s/n, 15782 Santiago de Compostela, Spain., Álvarez CV; Neoplasia & Endocrine Differentiation P0L5, Centre for research in Molecular Medicine and Chronic Disease (CIMUS), Av Barcelona s/n, 15782 Santiago de Compostela, Spain., Ildikó V; SeroScience Ltd, Budapest, Hungary., Urbanics R; SeroScience Ltd, Budapest, Hungary; Nanomedicine Research and Education Center, Department of Pathophysiology, Semmelweis University, Budapest, Hungary., Szebeni J; Nanomedicine Research and Education Center, Department of Translational Medicine, Semmelweis University, Budapest 1089, Hungary; Department of Nanobiotechnology and Regenerative Medicine, Faculty of Health Sciences, Miskolc University, Miskolc 2880, Hungary; School of Chemical Engineering and Translational Nanobioscience Research Center, Sungkyunkwan University, Suwon 16419, Republic of Korea., Alonso MJ; Center for Research in Molecular Medicine & Chronic Diseases (CIMUS), University of Santiago de Compostela, Campus Vida, 15782 Santiago de Compostela, Spain; Health Research Institute of Santiago de Compostela (IDIS), University of Santiago de Compostela, Campus Vida, 15782 Santiago de Compostela, Spain; Department of Pharmacology, Pharmaceutics and Pharmaceutical Technology, School of Pharmacy, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain. Electronic address: mariaj.alonso@usc.es.
Jazyk: angličtina
Zdroj: Journal of controlled release : official journal of the Controlled Release Society [J Control Release] 2025 Jan 10; Vol. 377, pp. 17-36. Date of Electronic Publication: 2024 Nov 17.
DOI: 10.1016/j.jconrel.2024.11.016
Abstrakt: 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.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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