Search Results (57)

This study aimed to analyze whether the enhancement of the biopharmaceutical efficiency of mebendazole, a poorly water-soluble anthelmintic drug, significantly improves its antiparasitic activity in a murine model of trichinellosis. Objectives: Two advanced oral formulations were developed, polyvinyl alcohol-derived nanoparticles (NP) and β-cyclodextrin citrate inclusion complexes (Comp), both employing mebendazole as an anthelmintic agent. The primary objective of this work is to treat trichinellosis, an infection with severe chronic effects. Methods: The physicochemical characteristics as well as the in vivo performance of the NP and Comp formulations were assessed. The in vivo studies involved the bioavailability analysis, comparing drug absorption between the pure drug and the novel formulations, as well as the in vitro anthelmintic activity and in vivo therapeutic efficacy against Trichinella spiralis encysted muscle larvae. The in vivo efficacy was evaluated during the parenteral stage of T. spiralis infection in male and female mice from two genetically distinct lines differing in mebendazole pharmacokinetic parameters and susceptibility to the parasite. Results: The formulations exhibited smaller particle sizes and improved dissolution properties compared to pure MBZ. The pharmacokinetics studies indicate that NP and Comp significantly improved MBZ bioavailability. Both NP and Comp significantly increased mebendazole’s anthelmintic activity against the encysted parasites, which would be attributed to the improved MBZ absorption. The formulations overcome the drug’s poor solubility and low bioavailability limitations, resulting in a higher plasma concentration of the active drug, even at low doses. Conclusions: These findings suggest that the newly designed mebendazole formulations are suitable for treating T. spiralis chronic infection and highlight a potential improvement in the pharmacological treatment of trichinellosis. Full article

Ulcerative colitis (UC) is a chronic inflammatory bowel disease associated with disrupted lipid metabolism. This study aimed to uncover novel molecular subtypes and biomarkers by integrating sphingolipid metabolism-related genes (SMGs) with machine learning approaches. Using data from the GEO and GeneCards databases, 29 UC-related SMGs were identified. Consensus clustering was employed to define distinct molecular subtypes of UC, and a diagnostic model was developed through various machine learning algorithms. Further analyses—including functional enrichment, transcription factor prediction, single-cell localization, potential drug screening, molecular docking, and molecular dynamics simulations—were conducted to investigate the underlying mechanisms and therapeutic prospects of the identified genes in UC. The analysis revealed two molecular subtypes of UC: C1 (metabolically dysregulated) and C2 (immune-enriched). A diagnostic model based on three key genes demonstrated high accuracy in both the training and validation cohorts. Moreover, the transcription factor FOXA2 was predicted to regulate the expression of all three genes simultaneously. Notably, mebendazole and NVP-TAE226 emerged as promising therapeutic agents for UC. In conclusion, SMGs are integral to UC molecular subtyping and immune microenvironment modulation, presenting a novel framework for precision diagnosis and targeted treatment of UC. Full article

Sparganosis is a neglected food- and water-borne zoonotic disease caused by members of the tapeworm genus Spirometra. More than 1600 human cases have been reported in the literature, primarily in Korea and China; however, the clinical significance of sparganosis is likely underestimated. The control of this disease is challenging in endemic regions because of the complexity of its lifecycle and the involvement of many animal host species, and treatment of clinical disease in humans and animals with selected drugs (e.g., mebendazole and/or praziquantel), even at elevated doses, is often ineffective, such that novel interventions are needed. It is anticipated that the use of molecular technologies should allow the identification of new intervention targets in crucial biological processes and/or pathways of Spirometra spp. While some draft genomes of Spirometra have been produced, their assemblies are incomplete. Here, we employed an advanced DNA sequencing–informatic approach to assemble and annotate the first high-quality genome of an isolate of Spirometra from Australia, with chromosome-level contiguity and a curated gene set. This improved genome provides a useful resource to support fundamental and applied molecular investigations of Spirometra species and should assist in the design of new tools for the intervention against sparganosis of companion animals (including dogs and cats) and humans. Full article

Cutaneous larva migrans (CLM) is attributed to zoonotic infection with animal hookworm larvae penetrating the human skin, usually the feet and legs. There is, however, a broad range of differential diagnoses, with the implicated hookworm species usually remaining speculative. Single-dose ivermectin is the most recommended current therapy, with repeat ivermectin doses sometimes required. With the massive global expansion of macrocytic lactone use in both livestock and companion animals, ivermectin resistance is being increasingly described in both helminths and ectoparasites. A case of CLM involving the foot of a healthy 37-year-old is described, with the failure of two doses of ivermectin 15 mg (240 μg/kg) a week apart. This occurred in the context of a remote work environment in tropical Australia with both companion animals (dogs and cats) and wildlife exposed to antiparasitic agents including ivermectin. A combination regimen of multiple doses of albendazole and ivermectin was curative. Parasites with multidrug resistance being described from animals now include hookworms in dogs which are resistant to pyrantel, benzimidazoles such as mebendazole and ivermectin. For relapsed CLM we now recommend a combination of ivermectin and albendazole therapy. This report supports the critical role for a One Health/Planetary Health approach to surveillance and response for emerging zoonoses and antimicrobial resistance in human and animal pathogens. This requires support for systematic approaches to foster and normalize communications and collaborations between human and animal health professionals, environmental scientists and ecologists and First Nations scientists who are the holders of Indigenous knowledge. Full article

Background: The COVID-19 pandemic necessitated the urgent exploration of therapeutic options, including drug repurposing. Anthelmintic drugs such as ivermectin and mebendazole have garnered interest due to their potential antiviral and immunomodulatory properties. However, conflicting evidence from randomized clinical trials (RCTs) necessitates a comprehensive meta-analysis to determine their efficacy and safety in COVID-19 management. Objective: This meta-analysis evaluates the clinical efficacy of ivermectin and mebendazole in treating COVID-19 by analyzing their impact on viral clearance, symptom resolution, hospitalization duration, and safety profiles. Methods: A systematic search of Scopus, PubMed, Embase, and the Cochrane Library was conducted following PRISMA guidelines to identify RCTs published up to February 2025. Eligible studies included adult patients with confirmed COVID-19 who received ivermectin or mebendazole compared with a placebo or standard of care. Data extraction and risk of bias assessment were performed using the Cochrane Risk of Bias Tool. Statistical heterogeneity was evaluated using the I² statistic, and pooled effect sizes were calculated for primary clinical outcomes. Results: Twenty-three RCTs (n = 12,345) were included, with twenty-one studies on ivermectin and two on mebendazole. The pooled analysis suggested no statistically significant improvement in viral clearance (p = 0.39), hospitalization duration (p = 0.15), or symptom resolution (p = 0.08) with ivermectin or mebendazole. However, individual studies indicated potential benefits, particularly for mebendazole, in reducing viral load and inflammation. Both drugs exhibited favorable safety profiles, with no significant increase in adverse events. Conclusions: The promising propensities observed in selected studies underscore the potential of ivermectin and mebendazole as adjunct therapies for COVID-19. With well-established safety profiles, immunomodulatory effects, and affordability, these drugs present strong candidates for further exploration. Advancing research through well-designed, large-scale RCTs will help unlock their full therapeutic potential and expand treatment options in the fight against COVID-19. Full article

Infections from the protozoa Entamoeba histolytica (E. histolytica), Giardia lamblia (G. lamblia), and Trichomonas vaginalis (T. vaginalis) pose a public health issue, with albendazole and mebendazole serving as the second-line medications for treating these parasitic infections. However, the low aqueous solubility of these compounds has led to the exploration of new strategies to enhance their solubility, with the formation of salts being a commonly employed strategy. The sulfonates A1, A2, and A3 of albendazole, along with M1, M2, and M3 of mebendazole, were synthesized. The antiparasitic activity in vitro was assessed against the trophozoites of E. histolytica, G. lamblia, and T. vaginalis. The salts A2, A3, M2, and M3 demonstrated a greater antiparasitic effect (IC₅₀ 37.95–125.53 µM) compared to the positive controls albendazole and mebendazole. The salts A1, A3, M2, and M3 do not exhibit cytotoxic effects at concentrations of 500 µM on the Vero cell line. Taken together, these findings indicate that the formation of these new solid saline phases enhances the antiparasitic effects in vitro, which is crucial in the current search for improved, safe, and effective antiparasitic agents. Full article

Background: Schistosomiasis (SCH) and soil transmitted helminthiasis (STH) have been targeted for elimination as a public health problem (EPHP) within the World Health Organization (WHO)’s Roadmap for Neglected Tropical Diseases (NTDs) 2021–2030. One of the global strategies for the control and elimination of these diseases is the mass administration of praziquantel and albendazole/mebendazole without prior individual diagnosis. To measure the progress towards the 2030 target, we conducted an assessment to determine the impact of the 3–5 rounds of annual mass drug administration among school age children in Ekiti State. Such scientific insights into the impact of these treatments will facilitate improved planning and targeting of resources towards reaching the last mile. Methodology: This assessment was conducted in 16 local government areas (LGAs) of Ekiti State between October and November 2023. Samples were collected from pupils in 166 primary and junior secondary schools across 166 wards of the State. Urine and stool samples were collected from 7670 pupils of ages 5 to 14 years, following standard laboratory procedures. Urine membrane filtration techniques were used for urine preparation while the Kato–Katz technique was used for stool preparation. A novel AiDx digital microscope was used to examine the presence of any ova in the prepared specimen. Parasite ova in urine were reported as the number of ova/10 mL of urine, and were categorized as light infection (˂50 ova/10 mL of urine) or heavy infection (>50 ova/10 mL of urine) while ova of parasites in stool samples were reported as eggs per gram of stool (EPG) and categorized into light, moderate and heavy infection. Results: Overall, 0.76% (0.56–0.95) at 95% CI of the 7670 respondents were infected with Schistosomia haematobium. No Schistosoma mansoni infection was recorded in the study. Similarly, 3.9% (3.43–4.29) at 95% CI were infected with STHs. The overall prevalence of schistosomiasis had significantly reduced from 8.2% in 2008 to 0.8%, while the overall prevalence of STHs significantly reduced from 30.9% to 3.9% with Ascaris lumbricoides being the dominant species of STH. In the 16 LGAs assessed, Ekiti West had the highest S. haematobium prevalence of 4.26%. Ise/Orun and Oye ranked second and third with a prevalence of 3.48% and 2.40% respectively, while all other LGAs had <1% prevalence. The prevalence of STHs was highest in Ekiti-West with a prevalence of 10.45% while Emure and Ikole Local Governments had the lowest prevalence of 0.31% and 0.38%, respectively. There was no significant difference in the prevalence of schistosomiasis between male (0.76%) and female (0.75%) as p ≥ 0.05. Similarly, the difference in prevalence for STH among males (3.95%) was not significantly different from their female counterparts (3.77%), p ≥ 0.05. Conclusions: Based on the WHO guidelines, this study demonstrated that only three LGAs require continued MDA every 2/3 years, seven require only surveillance while six are now non-endemic for schistosomiasis. Similarly, two of the LGAs require one round of MDA yearly, eight LGAs need one round of MDA every two to three years and six LGAs are now below the treatment threshold and no longer require treatment for STH. Full article

Drug resistance is the main challenge in treating parasitic diseases, including cystic echinococcosis (CE). Hence, the current study aims to investigate the effect of nanocapsules containing albendazole (ABZ), mebendazole (MBZ), and praziquantel (PZQ) on treating hydatid cysts in mice using these high-potency drugs. A total of 78 female white laboratory mice (BALB/C mice), 8 weeks old and weighing 25 g, were intraperitoneally injected with 1500 live protoscoleces of Echinococcus granulosus. The first group received ABZ nanocapsules, group 2 received MBZ nanocapsules, group 3 received PZQ nanocapsules, group 4 received ABZ + MBZ nanocapsules, group 5 received ABZ + PZQ nanocapsules, and group 6 received MBZ + PZQ nanocapsules. Each group also had a control group, which received the non-nanocapsulated drugs (group 7–12). Group 13 received no treatment and served as the negative control, just receiving phosphate-buffered saline (PBS). A thorough examination of the cysts’ physical properties, including size, quantity, and weight, was carried out. According to our results, the polymeric nanocapsules are sphere-like and of different sizes. The total number of cysts in all nanocapsule groups significantly decreased compared to the control group. In the total weight of the cysts, ABZ + MBZ nanocapsules, ABZ + PZQ nanocapsules, and MBZ + PZQ nanocapsules had the least total cyst weight, showing that the use of the medicinal combination had a better effect on the penetration and weight reduction of the cysts. In conclusion, the findings showed that ABZ, MBZ, and PZQ significantly reduced the size, weight, and number of hydatid cysts in the mouse model used in this study. Full article

Mebendazole (MBZ), a benzimidazole anthelmintic and cytoskeleton-disrupting compound, exhibits antitumor properties; however, its action on ovarian cancer (OC) is not clearly understood. This study evaluates the effect of MBZ on OC cell lines OVCAR3 and OAW42, focusing on cell proliferation, migration, invasion, and cancer stemness. The underlying mechanisms, including cytoskeletal disruption, epithelial–mesenchymal transition (EMT), and signaling pathways, were explored. MBZ inhibited OVCAR3 and OAW42 cell proliferation in a dose- and time-dependent manner. Additionally, MBZ significantly impedes migration, spheroid invasion, colony formation, and stemness. In addition, it reduced actin polymerization and down-regulated CSC markers (e.g., CD24, CD44, EpCAM). Moreover, MBZ suppressed MMP-9 activity and inhibited the EMT marker as judged by decreased N-Cadherin and Vimentin and increased E-Cadherin. Furthermore, MBZ induced G2/M cell cycle arrest by modulating Cyclin B1, CDC25C, and WEE1. Also, it triggered apoptosis by disrupting mitochondrial membrane potential. Mechanistic studies revealed a significant downregulation of Girdin, an Akt modulator, along with reduced p-Akt, p-IKKα/β, and p-NF-κB, indicating MBZ’s novel mechanism of action through the Girdin-mediated Akt/IKKα/β/NF-κB signaling axis. Thus, by targeting Girdin, MBZ presents a promising repurposed therapeutic strategy to inhibit cancer cell proliferation and metastasis in ovarian cancer. Full article

Background/Objectives: This study investigates the preparation of coamorphous systems composed entirely of active pharmaceutical ingredients (APIs), namely praziquantel, niclosamide, and mebendazole. The objective was to formulate and characterize binary and ternary coamorphous systems to evaluate their structural, thermal, and stability properties. Methods: Ten different mixtures (binary and ternary) were designed through a mixture design approach and prepared using a sustainable, one-step neat grinding process in a lab-scale vibrational mill. The systems were prepared reproducibly within 4 h across the entire experimental domain. Structural characterization was performed using PXRD and FTIR to confirm the absence of crystalline domains and the presence of molecular interactions. The glass transition temperature (T_g) was theoretically calculated using the Gordon–Taylor equation for three-component systems and determined experimentally via DSC. Stability studies were conducted on seven systems under different storage conditions (−30 °C, 5 °C, 25 °C, and 40 °C) for six months. Results: PXRD analysis confirmed the formation of coamorphous systems with no crystalline phases. DSC revealed a single T_g for most systems, indicating homogeneity. Stability studies demonstrated that five out of seven systems adhered to the “T_g—50 °C” stability rule, remaining physically stable over six months. Recrystallization studies indicated diverse pathways: some systems reverted to their original crystalline phases, while others formed new entities such as cocrystals. Conclusions: This study highlights the feasibility of coamorphous systems composed of multiple APIs using a simple, solvent-free grinding approach. The findings underscore the importance of molecular interactions in determining stability and recrystallization behavior, offering insights for designing robust coamorphous formulations. Full article

Drug repurposing is a strategy to discover new therapeutic uses for existing drugs, which have well-established toxicity profiles and are often more affordable. This approach has gained significant attention in recent years due to the high costs and low success rates associated with traditional drug development. Drug repositioning offers a more time- and cost-effective path for identifying new treatments. Several FDA-approved non-chemotherapy drugs have been investigated for their anticancer potential. Among these, anthelmintic benzimidazoles (such as albendazole, mebendazole, and flubendazole) have garnered interest due to their effects on microtubules and oncogenic signaling pathways. Blood cancers, which frequently develop resistance and have high mortality rates, present a critical need for effective therapies. This review highlights the recent advances in repurposing benzimidazoles for blood malignancies. These compounds induce cell cycle arrest, differentiation, tubulin depolymerization, loss of heterozygosity, proteasomal degradation, and inhibit oncogenic signaling to exert their anticancer effects. We also discuss current limitations and strategies to overcome them, emphasizing the potential of combining benzimidazoles with standard therapies for improved treatment of hematological cancers. Full article

Cystic echinococcosis still remains a serious health and economic problem worldwide. The etiologic agent is Echinococcus granulosus sensu lato, giving origin to a fluid-filled cystic lesion. Therapy faces several challenges. Nanodrugs have shown promise as chemotherapeutics against hydatid cysts. The present study evaluated a highly safe lipid nano-polymeric capsule for its superior efficacy and ability to overcome drug resistance. Nanocapsule drugs were formulated into six groups: Albendazole, mebendazole, praziquantel, albendazole + mebendazole, albendazole + praziquantel, and praziquantel + mebendazole. The protoscolicidal effects of these six groups were assessed at 10, 60, and 120 min in three concentrations (1, 0.5, and 0.25 mg/mL). Drug formulations were evaluated via zeta potential, droplet size, solubility, particle size analyzer (PSA), and scanning electron microscopy. According to the PSA results, the mean size of the albendazole nanocapsules was 193.01 nm, mebendazole was 170.40 nm, and praziquantel was 180.44 nm. Albendazole + mebendazole showed the greatest protoscolicidal activity at a concentration of 1 mg/mL after 120 min. In contrast, each drug’s 0.25 mg/mL single-dose times showed the least protoscolicidal activity after 120 min. With the right application of nanotechnology, it is possible to produce safe and effective drugs, such as the polymeric combination of albendazole and mebendazole, which has promising implications. Full article

Mebendazole (MBZ) is a benzimidazole carbamate anthelmintic used worldwide for the treatment and prevention of parasitic disorders in animals and humans. A large number of in vivo and in vitro studies have demonstrated that MBZ also has anticancer activity in multiple types of cancers. After oral administration, the phenylketone moiety of MBZ is rapidly reduced to the hydroxyl group to form the chiral hydroxy metabolite (MBZ-OH). To the best of our knowledge, there is no information in the literature on the stereochemical course of transformation and the anthelmintic and antitumor activity of individual enantiomers of MBZ-OH. In the present study, we describe in detail the direct HPLC resolution of MBZ-OH on a 100 mm × 4.6 mm Chirapak IG-3 column packed with 3 μm silica particles containing amylose (3-chloro-5-methylphenylcarbamate) as a selector. At 25 °C and using pure methanol as the mobile phase, the enantioseparation and resolution factors were 2.38 and 6.13, respectively. These conditions were scaled up at a semi-preparative scale using a 250 mm × 10 mm Chiralpak IG column to isolate multi-milligram amounts of both enantiomeric forms of the chiral metabolite. The chiroptical properties of the collected enantiomers were determined and, through a theoretical study, were related to the more stable conformations of MBZ-OH. The first and second eluted enantiomers were dextrorotatory and levorotatory, respectively, in dimethylformamide solution. Finally, by recording the retention factors of the enantiomers as the water content in the water–acetonitrile mobile phases was progressively varied, U-shaped retention maps were generated, indicating a dual and competitive hydrophilic interaction liquid chromatography and reversed-phase liquid chromatography retention mechanism on the Chirapak IG-3 chiral stationary phase. Full article

The production of small ruminant autochthonous breeds in the Centre region of Portugal is practiced in a semi-extensive husbandry system, exposing animals to parasitic infections. The main objective of this study was to estimate the prevalence of lungworm infection and identify risk factors. Fecal samples of 203 goats and 208 sheep from 30 herds were collected per rectum and subjected to the modified Baermann test. The overall prevalence of infection was 57.7%, significantly higher in goats (95.6%) than in sheep (20.7%) (p < 0.001). According to the binary logistic regression model, sheep dewormed with albendazole, mebendazole plus closantel, or ivermectin plus clorsulon presented a risk of Protostrongylidae infection 29.702, 7.426, or 8.720 times higher, respectively, than those dewormed with eprinomectin. Additionally, the presence of gastrointestinal parasites was investigated in 307 fecal samples using Mini-FLOTAC^®. The overall prevalence of infection was 86.3%, also significantly higher in goats (93.2%) than in sheep (79.9%) (p < 0.001). Strongyle-type eggs were the most frequently identified, both in sheep (69.8%) and goats (87.8%), followed by Eimeria oocysts (40.3% in sheep and 68.9% in goats). Considering the high prevalence and the burden of lungworm parasitic infection, it is urgent to determine its economic impact and the repercussions in animal health in the Centre region of Portugal to establish appropriate therapeutic guidelines. Full article

An estimated 1.5 billion people are infected with soil-transmitted helminths (hookworms, Ascaris lumbricoides and Trichuris trichiura). These infections are targeted for elimination by the World Health Organization (WHO) by 2030, with the main interventions being mass drug administration using albendazole or mebendazole. Tanzania is one of the endemic countries; it has been implementing MDA to school-aged children for more than a decade and the infection prevalence and intensity of infection have declined. Thus, at this point, the monitoring and evaluation of infection prevalence and intensity of infections, and assessing drug efficacy is crucial and requires accurate diagnostic tests. The currently used standard diagnostic test, the Kato–Katz (KK) technique, has several limitations and the WHO is calling for the development and evaluation of new diagnostic tests. The Lab-on-a-disk (LOD) was developed and tested in the endemic areas of north-western Tanzania to evaluate its sensitivity and specificity using KK and the formol-ether concentration technique. The results showed that when using a duplicate KK slide, the LOD had a sensitivity and specificity of 37.2% (95% CI: 30.7–43.9) and 67.3% (95% CI: 63.1–71.3%). Using four KK slides as a standard technique, the overall sensitivity and specificity were 37.7% (95% CI: 33.1–42.6) and 70.7% (95% CI: 65.5–75.6). The LOD attained high specificity but low sensitivity especially in detecting eggs of Trichuris trichiura. The LOD technique has potential as a promising diagnostic test, but its sensitivity still requires improvement. Full article