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

Document Type : Original Article

Authors

1 Departments of Medical Parasitology, Faculty of Medicine, Benha University, Benha, Cairo, Egypt

2 Departments of Medical Parasitology ,Faculty of Medicine, Benha University, Benha ,Egypt

3 Departments of Animal Reproduction , Research Centre

4 Departments of Zoonotic Diseases

5 Departments of Applied Organic Chemistry, Research Centre, Chemical Industries Research Institute Egypt

6 Departments of Medical Parasitology, Faculty of Medicine, Benha University, Benha

Abstract

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 1st
group (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 2nd
day post infection (PI) for 7 days. Daily stool examination for oocyst shedding from day 3 to 18 PI was
conducted to evaluate drugs’ efficacy. Furthermore, to confirm Cryptosporidium complete eradication, real
time PCR (RT-PCR) was performed on stool samples collected after 3 weeks PI. Survival rate was also
calculated for 3 weeks PI (at 7th, 14th and 21st d) to detect drugs’ efficacy. Besides, physical characterization
and 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 drugs
showed 88.4%, 66.7%, and 98.3% reduction, respectively. Additionally, RT-PCR revealed that the best
treatment 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 treated
groups.
Conclusion: The results indicated that Cu-BTC is an efficient delivery system that improved the efficacy
of the commonly used drugs.

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