Multi-drug loaded microneedles for emergency treatment of snakebite envenomation

Abstract

Snakebite envenomation is a WHO classified priority neglected disease, which manifests multiple local and systemic toxic effects. Intravenous antivenom therapy is the treatment of choice in clinical settings but it cannot be employed for pre-hospital management of envenomation cases due to certain limitations. On-field first-aid measures presently include use of pressure bandage immobilization (PBI), which has sub-optimal efficacy in managing snakebite casualties. There is therefore an urgent need for developing non-immunological, therapeutic interventions that could be self-administered immediately after snakebite, alone or in tandem with PBI, to reduce the morbidity and mortality. Venom toxins enter into the bloodstream via lymphatic pathway [e.g., high molecular weight (HMw) toxins] or directly ingress into the vasculature due to cytotoxic endothelium disruption [e.g., low molecular weight (LMw) toxins]. Recent literature has identified some pharmacological targets, which when applied topically impede the systemic absorption of HMw venom toxins by modulating lymphatic transit time, whereas a few others act as direct inhibitors of LMw toxins, when injected parentally. Based on available evidences our hypothesis shall lead to deliver formulation containing combination of drugs applied topically through convenient, self-administrated microneedles, either to delay absorption and lymphatic transit of HMw venom toxins into the bloodstream or to inhibit the mechanistic pathway of LMw toxins, and could therefore be more useful for pre-hospital management following snakebite as compared to PBI alone.