Abstract
Several antithrombotic drugs are available to treat cardiovascular diseases due to its high mortality and morbidity worldwide. Despite these, severe adverse effects that can lead to treatment withdrawal have been described, highlighting the importance of new therapies. Thus, this work describes the development of fucoidan microparticles containing acetylsalicylic acid (MP/F4M) for pulmonary delivery and in vitro, ex vivo, and in vivo evaluation. Microparticles were prepared via spray-drying and characterized in vitro (mucoadhesive properties, coagulation time, platelet aggregation, adhesion, and hemolysis) followed by ex vivo platelet aggregation, in vivo arterial thrombosis, and hemorrhagic profile. The formulation physicochemical characterization showed suitable characteristics along with delayed drug release, increased breathable particle fraction, and high washability resistance as well as antiplatelet activity and enhanced platelet adhesion in vitro. In in vivo assays, MP/F4M protected against arterial thrombosis, without changes in the hemorrhagic profile. Finally, no lung changes were observed after prolonged pulmonary administration, whereas isolated ASA led to an inflammatory response. In conclusion, pulmonary administration of fucoidan microparticles with an antiplatelet drug may be an alternative therapy to treat cardiovascular diseases, opening the field for different formulations.