دورية أكاديمية
أعرض في EDS

Probing the Biosafety of Implantable Artificial Secretory Granules for the Sustained Release of Bioactive Proteins.

التفاصيل البيبلوغرافية
العنوان: Probing the Biosafety of Implantable Artificial Secretory Granules for the Sustained Release of Bioactive Proteins.
المؤلفون: Álamo P; Institut d'Investigació Biomèdica Sant Pau (IIB SANT PAU), 08041 Barcelona, Spain.; Josep Carreras Leukaemia Research Institute (IJC), 08916 Badalona, Spain.; CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN, ISCIII), Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain., Parladé E; CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN, ISCIII), Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain.; Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain., Favaro MTP; Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain.; Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo 05508-000, Brazil., Gallardo A; Institut d'Investigació Biomèdica Sant Pau (IIB SANT PAU), 08041 Barcelona, Spain.; Department of Pathology, Hospital de la Santa Creu i Sant Pau, 08025 Barcelona, Spain., Mendoza R; CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN, ISCIII), Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain.; Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain., Ferreira LCS; Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo 05508-000, Brazil., Roher N; CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN, ISCIII), Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain.; Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain.; Department of Cell Biology, Animal Physiology and Immunology, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain., Mangues R; Institut d'Investigació Biomèdica Sant Pau (IIB SANT PAU), 08041 Barcelona, Spain.; Josep Carreras Leukaemia Research Institute (IJC), 08916 Badalona, Spain.; CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN, ISCIII), Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain., Villaverde A; CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN, ISCIII), Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain.; Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain.; Departament de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain., Vázquez E; CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN, ISCIII), Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain.; Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain.; Departament de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain.
المصدر: ACS applied materials & interfaces [ACS Appl Mater Interfaces] 2023 Aug 23; Vol. 15 (33), pp. 39167-39175. Date of Electronic Publication: 2023 Aug 10.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: American Chemical Society Country of Publication: United States NLM ID: 101504991 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1944-8252 (Electronic) Linking ISSN: 19448244 NLM ISO Abbreviation: ACS Appl Mater Interfaces Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Washington, D.C. : American Chemical Society
مواضيع طبية MeSH: Containment of Biohazards* , COVID-19*, Animals ; Humans ; Delayed-Action Preparations/pharmacology ; SARS-CoV-2 ; Prostheses and Implants ; Disease Models, Animal
مستخلص: Among bio-inspired protein materials, secretory protein microparticles are of clinical interest as self-contained, slow protein delivery platforms that mimic secretory granules of the human endocrine system, in which the protein is both the drug and the scaffold. Upon subcutaneous injection, their progressive disintegration results in the sustained release of the building block polypeptides, which reach the bloodstream for systemic distribution and subsequent biological effects. Such entities are easily fabricated in vitro by Zn-assisted cross-molecular coordination of histidine residues. Using cationic Zn for the assembly of selected pure protein species and in the absence of any heterologous holding material, these granules are expected to be nontoxic and therefore adequate for different clinical uses. However, such presumed biosafety has not been so far confirmed and the potential protein dosage threshold not probed yet. By selecting the receptor binding domain (RBD) from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein as a model protein and using a mouse lab model, we have explored the toxicity of RBD-made secretory granules at increasing doses up to ∼100 mg/kg of animal weight. By monitoring body weight and biochemical blood markers and through the histological scrutiny of main tissues and organs, we have not observed systemic toxicity. Otherwise, the bioavailability of the material was demonstrated by the induction of specific antibody responses. The presented data confirm the intrinsic biosafety of artificial secretory granules made by recombinant proteins and prompt their further clinical development as self-contained and dynamic protein reservoirs.
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فهرسة مساهمة: Keywords: drug delivery; protein engineering; protein materials; recombinant protein; self-assembling
المشرفين على المادة: 0 (Delayed-Action Preparations)
تواريخ الأحداث: Date Created: 20230824 Date Completed: 20230825 Latest Revision: 20230828
رمز التحديث: 20230828
مُعرف محوري في PubMed: PMC10450642
DOI: 10.1021/acsami.3c08643
PMID: 37614001
قاعدة البيانات: MEDLINE
الوصف
تدمد:1944-8252
DOI:10.1021/acsami.3c08643