Skip to main content

Self-Association of Endothelin-1 with Sterically Stabilized Phospholipid Nanomicelles Amplifies Its Hemodynamic Effects in Rats

Buy Article:

$113.00 plus tax (Refund Policy)

Abstract:

Endothelin-1 (ET-1) is a potent amphipathic vasoactive mammalian peptide. However, its hemodynamic effects in vivo are relatively short-lived most likely due to proteolytic degradation and inactivation. Accordingly, the purpose of this study was to determine whether self-association of ET-1 with long-circulating, biocompatible and biodegradable sterically stabilized phospholipid nanomicelles (SSM) composed distearoylphosphatidylethanolamine (DSPE-PEG2000) conjugated with poly(ethylene glycol) (molecular mass, 2,000) amplifies its systemic and regional hemodynamic effects in anesthetized rats. Solutions were infused at 0.1 ml/minute for 30 minutes. Infusion of SSM alone (0.1 ml/min for 30 min) had no significant effects of mean arterial pressure (MAP), heart rate, cardiac output (CO), total peripheral vascular resistance (TPR), and regional blood circulation. By contrast, infusion of ET-1 in SSM (50 ng/kg/min for 30 min) elicited a significant and prolonged increase in MAP and TPR, and a significant decrease in CO relative to infusion of ET-1 alone (P < 0.05). Likewise, ET-1 in SSM elicited a significant and prolonged decrease in blood flow coupled with a significant and prolonged increase in vascular resistance in the kidney and gastrointestinal tract relative to ET-1 alone (P < 0.05). By contrast, brain ET-1 in SSM-induced increase in vascular resistance in the brain which was significantly greater than that evoked by ET-1 in SSM (P < 0.05). Taken together, these data indicate that self-association of ET-1 with long-circulating, biocompatible and biodegradable SSM amplifies its hemodynamic effects in vivo and that these nanomicelles do not readily cross the intact blood-brain barrier. We suggest this new formulation of ET-1 could be used as a vasoconstrictor drug to treat hypovolemic shock and selectively reduce blood flow to cancer.

Keywords: BLOOD PRESSURE; DISTEAROYLPHOSPHATIDYLETHANOLAMINE; FORMULATION; NANOMEDICINE; NANOTECHNOLOGY; PEPTIDE; POLY(ETHYLENE GLYCOL); STABILITY; VASOMOTOR TONE

Document Type: Research Article

DOI: https://doi.org/10.1166/jbn.2007.033

Publication date: 2007-09-01

More about this publication?
  • Journal of Biomedical Nanotechnology (JBN) is a peer-reviewed multidisciplinary journal providing broad coverage in all research areas focused on the applications of nanotechnology in medicine, drug delivery systems, infectious disease, biomedical sciences, biotechnology, and all other related fields of life sciences.
  • Editorial Board
  • Information for Authors
  • Subscribe to this Title
  • Terms & Conditions
  • Ingenta Connect is not responsible for the content or availability of external websites
  • Access Key
  • Free content
  • Partial Free content
  • New content
  • Open access content
  • Partial Open access content
  • Subscribed content
  • Partial Subscribed content
  • Free trial content
Cookie Policy
X
Cookie Policy
Ingenta Connect website makes use of cookies so as to keep track of data that you have filled in. I am Happy with this Find out more