Fucoidan-incorporated dissolving microneedles: A novel approach to anticoagulant transdermal delivery

Abstract

Cardiovascular disease (CVD) is the leading cause of global mortality, particularly in Indonesia. Vascular disorders, including thrombosis and atherosclerosis, have been implicated as potential contributors to the development and progression of CVDs. Anticoagulant agents, such as heparin, have been commonly used to treat vascular disorders. Nevertheless, this agent may result in a hazardous adverse effect. Bioactive substances like fucoidan (FC) have emerged as an alternative, with anticoagulant and antithrombotic properties similar to heparin. However, FC was often found in oral, injectable, and transdermal dosage forms, which has considerable limitations due to its low bioavailability alongside with poor patient comfort and compliance. To overcome these issues, FC was further incorporated into dissolving microneedles (DMN) that can facilitate transdermal delivery of FC by penetrating the stratum corneum. Fucoidan Dissolving Microneedle (FC-DMN) was fabricated using gelatin and polyvinyl pyrrolidone (PVP) as polymers with various concentrations. Following several evaluations, FC-DMN exhibited good stability, mechanical resistance, and penetration ability. Ex vivo permeation study revealed that 91.23 ± 0.12 % of FC was released from the optimum formula. Furthermore, the hemolytic activity demonstrated that FC-DMN did not induce notably hemolytic, confirming its safe applicability. The in vivo anticoagulant activity test showed increased aPTT and PT values following a 7-day regimen of FC-DMN application. Interestingly, there were no significant differences (p > 0.05) were observed between FC-DMN and heparin injection (dosage 200 IU/Kg). In contrast, significant differences (p < 0.05) were observed when comparing FC-DMN to healthy controls, negative controls, and heparin gel. These findings suggested that FC-DMN offers a promising alternative to conventional anticoagulant therapies and can effectively deliver FC into systemic circulation. This study successfully developed a safe, painless, and nonirritating FC-DMN with promising results for enhancing the efficacy of anticoagulant therapy through the transdermal route.