Dual drug-loaded self-wearable electrospun nanofibers for synergistic pharmacological intervention through tertiary hemostasis in prehospital trauma care.

Abstract

Uncontrolled bleeding is a critical concern in both wartime and civilian trauma emergencies. Current mechanical hemostatic patches do not always suffice to control bleeding while also not addressing rebleeding, which is often observed during patient transportation. The unmet clinical need has led to exploration of drug-loaded hemostat dressings, providing mechanical hemostasis as well as drug delivery at the bleeding site to stabilize the clots. In the present study, hemostatic nanofiber patches of poly(vinyl alcohol)/chitosan/tranexamic acid-ethamsylate (PVA/CS/TXA-E) were prepared by taking a combination of chitosan, PVA, with two different hemostatic drugs, namely TXA, and ethamsylate to exert a synergistic pharmacological augmentation of hemostat performance of the nanofibers. The PVA/CS/TXA-E nanofiber patches comprised fiber strands with a 400 nm average diameter and showed a swelling ratio of 459%. The nanofiber possessed intermittent hydrophilicity (water contact angle 32). Drug release through the nanofiber followed a non-Fickian diffusion model. Dual-drug loaded nanofibers showed a decrease in the clotting time by 24%, while activated partial thromboplastin time, prothrombin time, and platelet recalcination time decreased by 6%, 20% & 15% over the single-drug loaded nanofibers. Cytocompatibility (80% and above) and hemocompatibility (less than 8%) of the patches were established. The hemorrhage control capacity was studiedin vitroand ex vivo on rabbit skin.In vivoresults corroborated the hemostat performance and evidence of the presence of granularity indicative of wound healing progression. Our results suggest PVA/CS/TXA-E potential as an effective hemostatic nanofiber with biocompatibility for managing hemorrhage and facilitating wound healing post-surgery.