Pharmacokinetics and biodistribution of a collagen-targeted peptide amphiphile for cardiovascular applications.

ABSTRACT: Atherosclerosis remains a leading cause of death and disability around the world and a major driver of health care spending. Nanomaterials have gained widespread attention due to their promising potential for clinical translation and use. We have developed a collagen-targeted peptide amphiphile (PA)-based nanofiber for the prevention of neointimal hyperplasia after arterial injury. Our goal was to characterize the pharmacokinetics and biodistribution of the collagen-targeted PA to further its advancement into clinical trials. Collagen-targeted PA was injected into the internal jugular vein of Sprague Dawley rats. PA concentrations in plasma collected at various times after injection (0 to 72 hours) were measured by liquid chromatography-tandem mass spectrometry. Pharmacokinetics of the collagen-targeted PA were characterized by a three-compartment model, with an extremely rapid apparent elimination clearance resulting in a plasma concentration decrease of more than two orders of magnitude within the first hour after injection. This rapid initial decline in plasma concentration was not due to degradation by plasma components, as collagen-targeted PA was stable in plasma ex vivo for up to 3 hours. Indeed, cellular blood components appear to be partly responsible, as only 15% of collagen-targeted PA were recovered following incubation with whole blood. Nanofibers in whole blood also adhered to red blood cells (RBCs) and were engulfed by mononuclear cells. This work highlights the unique pharmacokinetics of our collagen-targeted PA, which differ from pharmacokinetics of small molecules. Because of their targeted nature, these nanomaterials should not require sustained elevated plasma concentrations to achieve a therapeutic effect the way small molecules typically do.

SUBMITTER: Kassam HA 

PROVIDER: S-EPMC7580710 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature