Emergency treatment of NRBC victims by needle-free percutaneous administration of antidotes: AGATE Project (Atropine Gun AntidoTE)

Introduction
Large organophosphate intoxication of populations following terrorist attacks, requires the provision of pre-filled syringes of atropine sulfate for rapid patient management in hospitals. However, the extemporaneous preparation of these filled syringes is time consuming and not adapted in emergency context. As a result, a feasibility study of needle-free administration of atropine sulfate was carried out using an automated and multi-dose device. The aim of this work was to evaluate the tissue impact of injecting a solution into and through human skin sample using a spring injector^[1]. This study was complemented by a study of the transcutaneous absorption of a solution of atropine sulfate (1 mg/mL) commonly used in the treatment of organophosphate intoxications.

Materials and Methods
The injection of an aqueous solution into and through the skin was studied by (i) visualizing the epidermal entry and hypodermal exit impact of a 0.01% Blue Brillant dye solution, (ii) the cutaneous and transcutaneous distribution of a 1 mL solution of atropine sulfate 1 mg/mL injected in 0.1 second through a human skin sample held on a Franz cell. The volume and concentration of atropine in the liquid of the Franz cell’s receptor compartment were detected using a high-performance liquid chromatography method.

Results/Discussion
Transcutaneous injection of a Blue Brillant solution results in the formation of an epidermal and hypodermal orifice of size 0.6 mm (23 G) and 1.7 mm (17 G) respectively. After injection of 1 mL of atropine sulfate solution, 0.9 mL of this solution was collected in the recipient compartment of Franz cells. The amount of atropine not detected in the recipient compartment was explained by adsorption of the active ingredient e.g. on the device walls and soluble proteins (between 14 and 44%).

Conclusion
Currently used in animals, the automated spring needleless injector is a suitable device for the immediate, rapid and effective treatment of patients intoxicated by organophosphates. In a medical emergency context, this device offers considerable advantages in terms of ease of use and rapid injection.

^[1] Phatale V, Vaiphei KK, Jha S, Patil D, Agrawal M, Alexander A. Overcoming skin barriers through advanced transdermal drug delivery approaches. J Controlled Release. nov 2022;351:361‑80.

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