The combination of carvacrol and albendazole enhanced the efficacy of monotherapy in experimental alveolar echinococcosis

Lopez, Lurdes Milagros; Pensel, Patricia Eugenia; Fabbri, Julia; Albani, Clara; Elissondo, Natalia; Gambino, Guillermo; Elissondo, Marı́a Celina

doi:10.1016/j.actatropica.2021.106198

Cited by 12 publications

(4 citation statements)

References 46 publications

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“…A metacestode was scored as dead when its germinal layer was collapsed and clearly peeled off from the laminated layer. 20 , 21 …”

Section: Methodsmentioning

confidence: 99%

Oral Delivery of Anti-Parasitic Agent-Loaded PLGA Nanoparticles: Enhanced Liver Targeting and Improved Therapeutic Effect on Hepatic Alveolar Echinococcosis

Li¹,

Yang²,

Han³

et al. 2023

IJN

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Background Alveolar echinococcosis (AE) is a lethal parasitic disease caused by infection with the metacestode of the dog/fox tapeworm Echinococcus multilocularis , which primarily affects the liver. Although continued efforts have been made to find new drugs against this orphan and neglected disease, the current treatment options remain limited, with drug delivery considered a likely barrier for successful treatment. Methods Nanoparticles (NPs) have gained much attention in the field of drug delivery due to their potential to improve delivery efficiency and targetability. In this study, biocompatible PLGA nanoparticles encapsulating a novel carbazole aminoalcohol anti-AE agent (H1402) were prepared to promote the delivery of the parent drug to liver tissue for treating hepatic AE. Results H1402-loaded nanoparticles (H1402-NPs) had a uniform spherical shape and a mean particle size of 55 nm. Compound H1402 was efficiently encapsulated into PLGA NPs with a maximal encapsulation efficiency of 82.1% and drug loading content of 8.2%. An in vitro uptake assay demonstrated that H1402-NPs rapidly penetrated the in vitro cultured pre-cyst wall and extensively accumulated in the pre-cysts of E. multilocularis within only 1 h. The biodistribution profile of H1402-NPs determined through ex vivo fluorescence imaging revealed significantly enhanced liver distribution compared to unencapsulated H1402, which translated to improved therapeutic efficacy and reduced systemic toxicity (especially hepatotoxicity and cytotoxicity) in a hepatic AE murine model. Following a 30-day oral regimen (100 mg/kg/day), H1402-NPs significantly reduced the parasitic burden in both the parasite mass (liver and metacestode total weight, 8.8%) and average metacestode size (89.9%) compared to unmedicated infected mice (both p -values < 0.05); the treatment outcome was more effective than those of albendazole- and free H1402-treated individuals. Conclusion Our findings demonstrate the advantages of encapsulating H1402 into PLGA nanoparticles and highlight the potential of H1402-NPs as a promising liver-targeting therapeutic strategy for hepatic AE.

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“…A metacestode was scored as dead when its germinal layer was collapsed and clearly peeled off from the laminated layer. 20 , 21 …”

Section: Methodsmentioning

confidence: 99%

Oral Delivery of Anti-Parasitic Agent-Loaded PLGA Nanoparticles: Enhanced Liver Targeting and Improved Therapeutic Effect on Hepatic Alveolar Echinococcosis

Li¹,

Yang²,

Han³

et al. 2023

IJN

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“…Another study showed that compound 25 in combination with ABZ was more effective against E. multilocularis metacestodes in vitro and infected mice. The combination reduced the weight of metacestodes by 83% (Albani et al., 2023; Lopez et al., 2022).…”

Section: Terpene Combination Therapy Against Echinococcosismentioning

confidence: 99%

Could natural terpenes be an alternative for the treatment of neglected tropical diseases?

Soto‐Sánchez

2024

Chem Biol Drug Des

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Existing chemotherapy for neglected tropical diseases (NTDs) can often be toxic and ineffective, highlighting the necessity for new treatments. Terpenes are secondary metabolites with pharmacological potential. This aim of this mini‐review is to explore the most promising natural terpenes with anti‐leishmanicidal, anti‐schistosomicidal, and anti‐echinococcal activity, their mechanisms of action, and their efficacy as combination therapy. The study identified a tetracyclic diterpenoid, a sesquiterpene lactone, and a triterpene with the highest biological activity against leishmaniasis. Additionally, a triterpenoid and a tetraterpene showed potent activity against schistosomiasis and echinococcosis, respectively. Compounds have antiparasitic effects by inducing cell death, inhibiting cell stress‐related proteins, degrading extracellular matrix, and modulating immune and inflammatory responses. The employment of combination therapy and terpene nanotransporters appears to enhance the antiparasitic activity of these compounds. Although identifying specific molecular targets is necessary, the use of terpenes in combination therapy presents a safe and highly promising approach for the rational development of more potent and selective antiparasitic drugs.

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“…Other methods were applied combining the drug into lipid-based drug delivery systems (Will Castro et al, 2021); and complexing the drug with cyclodextrin (Kalaiselvan et al, 2007 andEid et al, 2020). Essential oils are natural and complex mixtures of compounds from aromatic plant parts, in a study by Lopez et. al., (2022), carvacrol (a phenolic monoterpenoid in lots of essential oils) and albendazole combination were used to enhance the efficacy of albendazole.…”

Section: Conventional Treatment Of Trichinellosismentioning

confidence: 99%

A mini Review of New Potential Therapeutic Strategies Against Trichinellosis

Ebrahim,

Elkhawass,

Nabil

et al. 2024

Egyptian Academic Journal of Biological Sciences, B. Zoology

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Trichinella spiralis is a parasitic nematode transmitted through the consumption of contaminated meat. The study aims to provide comprehensive information on various aspects of trichinellosis, including its manifestations, conventional treatment methods, and emerging antitrichinellosis strategies using nanoparticles is a promising approach to overcoming the challenges posed by conventional trichinellosis treatments. The infection begins when a host ingests meat containing infective larvae of T. spiralis. The adult worms release newborn larvae (NBL) that enter the bloodstream. These NBL invade striated skeletal muscle cells and establish nurse cell-parasite complexes within the muscle tissue. Trichinella causes a public health impact and economic costs related to pig husbandry and food safety. As the prevalence of trichinellosis remains a concern, continued research, surveillance, and public awareness efforts are essential to mitigate the impact of this parasitic infection on human health and the food industry. Pursuing new and effective treatments for trichinellosis remains imperative, and ongoing research efforts are exploring innovative strategies to address the limitations of existing drugs and enhance their therapeutic outcomes. Several studies highlight the potential of specific antigens for developing vaccines that could offer protective immunity against T. spiralis infection, providing valuable insights for future research in parasitology and vaccine development. In conclusion, the integration of nanotechnology and nanoparticles holds promise for revolutionizing drug delivery systems, improving therapeutic outcomes, and offering novel approaches to treat various diseases, including parasitic infections like trichinellosis. Ongoing research in this field is likely to unveil more innovative applications and solutions in the future.

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The combination of carvacrol and albendazole enhanced the efficacy of monotherapy in experimental alveolar echinococcosis

Cited by 12 publications

References 46 publications

Oral Delivery of Anti-Parasitic Agent-Loaded PLGA Nanoparticles: Enhanced Liver Targeting and Improved Therapeutic Effect on Hepatic Alveolar Echinococcosis

Oral Delivery of Anti-Parasitic Agent-Loaded PLGA Nanoparticles: Enhanced Liver Targeting and Improved Therapeutic Effect on Hepatic Alveolar Echinococcosis

Could natural terpenes be an alternative for the treatment of neglected tropical diseases?

A mini Review of New Potential Therapeutic Strategies Against Trichinellosis

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