Systemic peptide amphiphile nanofiber delivery following subcutaneous injection.

Autor: Barlek MH; Department of Surgery, University of Virginia, Charlottesville, VA, 22903, USA., Gillis DC; Department of Surgery, University of Virginia, Charlottesville, VA, 22903, USA., Egner SA; Department of Materials Science and Engineering, Northwestern University, Evanston, IL, 60208, USA., Maragos SL; Department of Surgery, University of Virginia, Charlottesville, VA, 22903, USA., Karver MR; Simpson Querrey Institute for BioNanotechnology, Northwestern University, Chicago, IL, 60611, USA; Department of Medicine, Northwestern University, Chicago, IL, 60611, USA., Stupp SI; Department of Materials Science and Engineering, Northwestern University, Evanston, IL, 60208, USA; Departments of Chemistry and Biomedical Engineering, Northwestern University, Evanston, IL, 60208, USA; Simpson Querrey Institute for BioNanotechnology, Northwestern University, Chicago, IL, 60611, USA; Department of Medicine, Northwestern University, Chicago, IL, 60611, USA., Tsihlis ND; Department of Surgery, University of Virginia, Charlottesville, VA, 22903, USA; Department of Biomedical Engineering, University of Virginia, Charlottesville, VA, 22904, USA., Kibbe MR; Department of Surgery, University of Virginia, Charlottesville, VA, 22903, USA; Department of Biomedical Engineering, University of Virginia, Charlottesville, VA, 22904, USA. Electronic address: melinakibbe@virginia.edu.
Jazyk: angličtina
Zdroj: Biomaterials [Biomaterials] 2023 Dec; Vol. 303, pp. 122401. Date of Electronic Publication: 2023 Nov 18.
DOI: 10.1016/j.biomaterials.2023.122401
Abstrakt: Peptide amphiphile (PA) nanofibers have been shown to target and deliver drugs when administered via an intravenous (IV) injection. Subcutaneous administration can broaden the applicability of PA nanofibers in the medical field. The ability of PA nanofibers to be absorbed into systemic circulation after subcutaneous administration was investigated. Four PA molecules with different amino acid sequences were designed to understand the effect of nanofiber cohesion and charge on uptake. Solution small-angle X-ray scattering confirmed nanostructure morphology and provided characteristic lengths for co-assemblies. Circular dichroism and solution wide-angle X-ray scattering confirmed PA secondary structure and molecular order. PAs were co-assembled in a 95 %:5 % molar ratio of unlabeled PA to fluorescently labeled PA. Male and female Sprague Dawley rats were injected in the nape of the neck with PA co-assemblies. In vivo normalized abdominal fluorescence was measured 1-72 h after injection. PA nanofibers with a negative charge and low internal order showed the highest amount of systemic absorption at 1, 6, and 24 h. At 24 h after injection, white blood cell count decreased and glucose was elevated. Glucose began to decrease at 48 h. These data indicate that PA nanofibers can be absorbed into the systemic circulation after subcutaneous injection.
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.
(Published by Elsevier Ltd.)
Databáze: MEDLINE
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