Fabrication and Evaluation of Rapidly Dissolving Microneedles Loaded with Organophosphorus Hydrolase for the Treatment of Transdermal Ethyl Paraoxon Poisoning

Background: Given the severe toxicity of organophosphates and the efficient catalytic hydrolysis of organophosphates by organophosphorus hydrolase (OPH) against them, a rapidly dissolving microneedle patch loaded with OPH offers a promising therapeutic strategy to provide timely detoxification conveniently. Methods: The microneedles were prepared with sulfobutylether-β-cyclodextrin (SCD) matrix to load OPHDS5, one of the mutants of OPH, and were characterized in vitro and in vivo to determine tip loading capacity, skin insertion efficiency, and protective efficacy against ethyl paraoxon poisoning. Results: Microneedles prepared with 60% w/v SCD displayed well-defined square-pyramidal tips and a mechanical strength of 4 N/needle at 1200 μm. When containing 1.2 mg OPHDS5, the microneedles enabled SD rats to completely survive a lethal challenge of ethyl paraoxon, achieving a 100% survival rate, significantly alleviating the symptoms resulting from transdermal exposure and markedly attenuating the symptoms resulting from transdermal exposure. Conclusions: A rapidly dissolving microneedle patch encapsulating OPH was successfully developed. The patch effectively penetrated the skin and exhibited robust prophylactic and therapeutic activity against ethyl paraoxon poisoning.