Systemic peptide amphiphile nanofiber delivery following subcutaneous injection

Biomaterials. 2023 Nov 18;303:122401. doi: 10.1016/j.biomaterials.2023.122401. Online ahead of print.ABSTRACTPeptide 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.PMID:38006645 | DOI:10.1016/j.b...

Source: Biomaterials - November 25, 2023 Category: Materials Science Authors: Mark H Barlek David C Gillis Simon A Egner Sophia L Maragos Mark R Karver Samuel I Stupp Nick D Tsihlis Melina R Kibbe Source Type: research