ArticleDrug design, development and therapy2025
A Dual-Targeted Therapy with Fucoidan-Functionalized Thrombolytic Discoidal Microparticles for Pulmonary Thromboembolism.
Article in Drug design, development and therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Pulmonary thromboembolism, a pathological condition characterized by the occlusion of pulmonary vasculature by free-circulating thrombus, constitutes the third leading cause of cardiovascular-related mortality. Among conventional therapeutic approaches to manage the disease, systemic intravenous thrombolysis is hindered by inherent pharmacokinetic and pharmacodynamic limitations, including a short biological half-life, high requisite dosages, and an increased risk of hemorrhagic transformation. Given the critical need for prompt pulmonary reperfusion, this study introduces a dual-targeted therapeutic strategy employing fucoidan-functionalized, thrombolytic discoidal polymeric microparticles. This dual-targeted approach leverages the physicochemical properties of disc-shaped particles, which exhibit shape-dependent accumulation in the lungs, together with the biological binding affinity provided by the marine-derived component, fucoidan. Methods: A top-down lithographic fabrication technique was employed to synthesize discoidal microparticle systems for physicochemical targeting to the pulmonary vasculature, providing precise control over the system's geometry and uniform drug encapsulation efficiency. Furthermore, a PLGA polymeric matrix was positively modified to incorporate fucoidan onto its matrix surface, which is a sulfated polysaccharide with high-affinity interactions for P-selectin expressed on activated platelets in the nanomolar range. In vitro and in vivo thrombolysis assays were conducted to assess the therapeutic efficacy of microparticles. Results: The proposed discoidal systems coupled with the fucoidan showed rapid accumulation due to their shape and selective interaction with activated platelets. Approximately 50% of the injected microparticles exhibited preferential accumulation within 15 minutes post-injection, and a significant portion remained over assay times. The fucoidan functionalization enhanced the targeting potential, yielding a 4.65- and 1.48-fold increase under static and dynamic flow assays, respectively (all Conclusion: The proposed systems may offer an alternative to conventional systemic thrombolysis coupled with adjunctive pharmacological interventions.
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