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Engineering of plasminogen activators for targeting to thrombus and heightening thrombolytic efficacy

S Absar1, N Gupta1, K Nahar1

  • 1Department of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, TX, USA.

Journal of Thrombosis and Haemostasis : JTH
|June 16, 2015
PubMed

Insights

Developing targeted plasminogen activators (PAs) aims to dissolve blood clots effectively while minimizing bleeding risks. This review explores strategies for safer, more specific thrombolytic therapies.

Area of Science:

  • Biotechnology
  • Cardiovascular Medicine
  • Pharmacology

Background:

  • Acute myocardial infarction, caused by coronary artery thrombosis, is a leading cause of death.
  • Current treatments use intravenous plasminogen activators (PAs) that lack specificity, leading to bleeding complications.
  • The indiscriminate action of PAs depletes clotting factors and induces a systemic lytic state.

Purpose of the Study:

  • To review strategies for developing thrombus-specific plasminogen activators (PAs).
  • To discuss methods for attenuating bleeding risks associated with thrombolytic therapy.
  • To explore advancements in drug delivery systems for thrombolytic agents.

Main Methods:

  • Review of biotechnological approaches including mutant and chimeric PAs.
  • Investigation of antibody-mediated targeting of thrombi.
  • Analysis of particulate carrier-based systems and triggered-release concepts.

Main Results:

  • Various strategies have been developed to enhance thrombus selectivity of PAs.
  • Biotechnological modifications and targeted delivery systems show promise in improving efficacy and safety.
  • Accomplishments in developing patient-friendly delivery systems for thrombolytic drugs are described.

Conclusions:

  • Continued research into targeted thrombolytic therapies is crucial for reducing bleeding complications.
  • Novel strategies and delivery systems are advancing the field of thrombolytic drug development.
  • The development of safer and more effective thrombolytic agents holds significant clinical potential.

Keywords:
bleedingfibrinolytic agentsmolecular targeted therapythrombolytic therapytissue plasminogen activator

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