Nitazoxanide 100mg/5ml oral suspension

Cryptosporidium spp. is a cause of diarrhea morbidity and mortality in children under 5 years of age. In addition, asymptomatic infections can have a negative impact on growth and development. In low- and middle-income countries where a greater number of infants may be malnourished, the results of treating cryptosporidiosis with the only Food and Drug Administration-approved drug nitazoxanide (NTZ) have been inconsistent. Malnutrition is both a risk factor for cryptosporidiosis and a consequence of infection with this parasite. Treatment with the probiotic Lactobacillus reuteri DSM 17938 has been shown to assist in nutritional recovery and the restoration of gut health. In this pilot randomized clinical trial, we examined whether combined probiotic and NTZ treatment could result in the reduction in parasitemia and infection-associated growth stunting in undernourished children. Cryptosporidium spp.-positive Bangladeshi children with a weight-for-length Z score between -1 and -3 were randomly assigned to one of three groups. Group 1 (n = 26) received NTZ and Lactobacillus, group 2 (n = 28) received NTZ along with a placebo, and the third control group (n = 10) received standard care. There was no difference in the duration of infection or improvement in child anthropometric measurements in any treatment group compared with control. Therefore, this pilot study does not provide support for treatment with NTZ, Lactobacillus, or the two in combination as an effective means of reducing the duration of Cryptosporidium spp. infection or improving growth in growth-stunted children.

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Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) poses a major threat to the global swine industry, yet effective prevention and control measures remain elusive. This study unveils Nitazoxanide (NTZ) as a potent inhibitor of PRRSV both in vitro and in vivo. Through High-Throughput Screening techniques, 16 potential anti-PRRSV compounds are identified from a library comprising FDA-approved and pharmacopeial drugs. We show that NTZ displays strong efficacy in reducing PRRSV proliferation and transmission in a swine model, alleviating viremia and lung damage. Additionally, Tizoxanide (TIZ), the primary metabolite of NTZ, has been identified as a facilitator of NMRAL1 dimerization. This finding potentially sheds light on the underlying mechanism contributing to TIZ's role in augmenting the sensitivity of the IFN-β pathway. These results indicate the promising potential of NTZ as a repurposed therapeutic agent for Porcine Reproductive and Respiratory Syndrome (PRRS). Additionally, they provide valuable insights into the antiviral mechanisms underlying NTZ's effectiveness.

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This paper presents potentially informative findings of the applicability of nitazoxanide in reducing viral load in patients with mild COVID-19. However, the reviewer raised concerns regarding the methods of analysis used in the study which may have had misleading implications

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PurposeAnti-leishmanial medications administered by oral and parenteral routes are less effective for treatment of cutaneous leishmaniasis (CL) and cause toxicity, hence targeted drug delivery is an efficient way to improve drug availability for CL with reduced toxicity. This study aimed to develop, characterize and evaluate nitazoxanide and quercetin co-loaded nanotransfersomal gel (NTZ-QUR-NTG) for the treatment of CL.MethodsNTZ-QUR-NT were prepared by thin film hydration method and were statistically optimized using Box-Behnken design. To ease the topical delivery and enhance the retention time, the NTZ-QUR-NT were dispersed in 2 % chitosan gel. Moreover, in-vitro drug release, ex-vivo permeation, macrophage uptake, cytotoxicity and anti-leishmanial assays were performed.ResultsThe optimized formulation indicated mean particle size 210 nm, poly dispersity index (PDI) 0.16, zeta potential (ZP) −15.1 mV and entrapment efficiency (EE) of NTZ and QUR was 88 % and 85 %, respectively. NTZ-QUR-NT and NTZ-QUR-NTG showed sustained release of the incorporated drugs as compared to the drug dispersions. Skin permeation of NTZ and QUR in NTZ-QUR-NTG was 4 times higher in comparison to the plain gels. The NTZ-QUR-NT cell internalization was almost 10-folds higher than NTZ-QUR dispersion. The cytotoxicity potential (CC50) of NTZ-QUR-NT (71.95 ± 3.32 μg/mL) was reduced as compared to NTZ-QUR dispersion (49.77 ± 2.15 μg/mL. A synergistic interaction was found between NTZ and QUR. Moreover, in-vitro anti-leishmanial assay presented a lower IC50 value of NTZ-QUR-NT as compared to NTZ-QUR dispersion. Additionally, a significantly reduced lesion size was observed in NTZ-QUR-NTG treated BALB/c mice, indicating its antileishmanial potential.ConclusionIt can be concluded that nanotransfersomal gel has the capability to retain and permeate the incorporated drugs through stratum corneum and induce synergetic anti-leishmanial effect of NTZ and QUR against cutaneous leishmaniasis.

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Abstract Background Castration-resistant prostate cancer often metastasizes to the bone, and such bone metastases eventually become resistant to available therapies, leading to the death of patients. Enriched in the bone, TGF-β plays a pivotal role in bone metastasis development. However, directly targeting TGF-β or its receptors has been challenging for the treatment of bone metastasis. We previously found that TGF-β induces and then depends on the acetylation of transcription factor KLF5 at K369 to regulate multiple biological processes, including the induction of EMT, cellular invasiveness, and bone metastasis. Acetylated KLF5 (Ac-KLF5) and its downstream effectors are thus potential therapeutic targets for treating TGF-β-induced bone metastasis in prostate cancer. Methods A spheroid invasion assay was applied to prostate cancer cells expressing KLF5 K369Q , which mimics Ac-KLF5, to screen 1987 FDA-approved drugs for invasion suppression. Luciferase- and KLF5 K369Q -expressing cells were injected into nude mice via the tail artery to model bone metastasis. Bioluminescence imaging, micro-CT), and histological analyses were applied to monitor and evaluate bone metastases. RNA-sequencing, bioinformatic, and biochemical analyses were used to understand nitazoxanide (NTZ)-regulated genes, signaling pathways, and the underlying mechanisms. The binding of NTZ to KLF5 proteins was evaluated using fluorescence titration, high-performance liquid chromatography (HPLC), and circular dichroism (CD) analysis. Results NTZ, an anthelmintic agent, was identified as a potent invasion inhibitor in the screening and validation assays. In KLF5 K369Q -induced bone metastasis, NTZ exerted a potent inhibitory effect in preventive and therapeutic modes. NTZ also inhibited osteoclast differentiation, a cellular process responsible for bone metastasis induced by KLF5 K369Q . NTZ attenuated the function of KLF5 K369Q in 127 genes’ upregulation and 114 genes’ downregulation. Some genes’ expression changes were significantly associated with worse overall survival in patients with prostate cancer. One such change was the upregulation of MYBL2 , which functionally promotes bone metastasis in prostate cancer. Additional analyses demonstrated that NTZ bound to the KLF5 protein, KLF5 K369Q bound to the promoter of MYBL2 to activate its transcription, and NTZ attenuated the binding of KLF5 K369Q to the MYBL2 promoter. Conclusions NTZ is a potential therapeutic agent for bone metastasis induced by the TGF-β/Ac-KLF5 signaling axis in prostate cancer and likely other cancers.

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