Nano copper-organic framework as a delivery system to improve the efficiency of commercially available drugs for cryptosporidiosis: In vivo experimental study

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Background: Considering low efficacy, and high toxicity of the commonly used drugs in cryptosporidiosis,in addition to the development of drug resistance, trial for a novel approach is required.Objective: To evaluate the efficacy of Nifuroxazide (Antinal), Trimethoprim-Sulfamethoxazole (Septrin),Nitazoxanide (NTZ), loaded-on copper-benzene tricarboxylate (Cu-BTC) metal organic frameworks(MOH) for treatment of Cryptosporidium-experimentally infected mice.Material and Methods: Ninety male Swiss albino mice were divided into nine groups. Except for the 1stgroup (control negative), all mice were infected with 103 Cryptosporidium oocysts. Except for 2nd group < br />(infected non treated), the remaining groups of infected mice were administered the tested drugs 2ndday post infection (PI) for 7 days. Daily stool examination for oocyst shedding from day 3 to 18 PI wasconducted to evaluate drugs’ efficacy. Furthermore, to confirm Cryptosporidium complete eradication, realtime PCR (RT-PCR) was performed on stool samples collected after 3 weeks PI. Survival rate was alsocalculated for 3 weeks PI (at 7th, 14th and 21st d) to detect drugs’ efficacy. Besides, physical characterizationand toxicity of Cu-BTC were performed before mice treatment.Results: Electron micrographs revealed 300-500 nm pyramidal crystals of Cu-BTC. Non-loaded Antinal,Septrin, and NTZ showed 67.2%, 62.2% and 76.6% reduction in oocyst shedding, while loaded drugsshowed 88.4%, 66.7%, and 98.3% reduction, respectively. Additionally, RT-PCR revealed that the besttreatment for cryptosporidiosis was NTZ@Cu-BTC, followed by antinal@Cu-BTC. Interestingly, using Cu-BTC alone had a relative positive therapeutic effect. Concerning the survival rate, Cu-BTC alone had 90%total survival that increased to100% when Cu-BTC was incorporated with studied drugs in all treatedgroups.Conclusion: The results indicated that Cu-BTC is an efficient delivery system that improved the efficacyof the commonly used drugs.