In vitro efficacy of albendazole-loaded β-cyclodextrin against protoscoleces of Echinococcus granulosus sensu stricto

Nayer Mehdizad Bakhtiar; Abolfazl Akbarzadeh; Ehsan Ahmadpour; Mahmoud Mahami-Oskouei; Adriano Casulli; Roghayeh Norouzi; Milad Asadi; Mina Ebrahimi; Nahideh Asadi; Sonia M Rodrigues Oliveira; Maria de Lourdes Pereira; Adel Spotin

doi:10.1016/j.exppara.2022.108428

In vitro efficacy of albendazole-loaded β-cyclodextrin against protoscoleces of Echinococcus granulosus sensu stricto

Exp Parasitol. 2022 Dec:243:108428. doi: 10.1016/j.exppara.2022.108428. Epub 2022 Nov 13.

Affiliations

¹ Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Parasitology and Mycology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
² Health Research Center, Chamran Hospital, Tehran, Iran; Department of Medical Nanotechnology, Faculty of Advanced Medical Science, Tabriz University of Medical Sciences, Tabriz, Iran.
³ Infectious and Tropical Disease Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
⁴ Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
⁵ WHO Collaborating Centre for the Epidemiology, Detection and Control of Cystic and Alveolar Echinococcosis, Department of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy; European Reference Laboratory for Parasites, Department of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy.
⁶ Department of Pathobiology, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran.
⁷ Department of Basic Oncology, Health Institute of Ege University, Izmir, Turkey.
⁸ Department of Parasitology and Mycology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
⁹ Department of Medical Nanotechnology, Faculty of Advanced Medical Science, Tabriz University of Medical Sciences, Tabriz, Iran.
¹⁰ CICECO - Aveiro Institute of Materials, University of Aveiro, 3810-193, Aveiro, Portugal.
¹¹ Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Parasitology and Mycology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address: Adelespotin@gmail.com.

PMID: 36384195
DOI: 10.1016/j.exppara.2022.108428

Abstract

Background: Cystic echinococcosis (CE), a widespread helminthic disease caused by the larval stage of the dog tapeworm Echinococcus granulosus represents a public health concern in humans. Albendazole (ABZ) is the first-line treatment for CE; however therapeutic failure of ABZ against CE occurs because of size and location of formed cysts as well its low aqueous solubility and consequently its erratic bioavailability in plasma. Serious adverse effects have also been observed following the long-term use of ABZ in vivo.

Methods: We evaluated the apoptotic effects of ABZ-loaded β-cyclodextrin (ABZ-β-CD) against protoscoleces (PSCs) versus ABZ alone. After 15 h of exposure, Caspase-3 enzymatic activity was determined by fluorometric assay in PSCs treated with ABZ and ABZ-β-CD groups. To assess the treatment efficacy of ABZ-β-CD against PSCs, mRNA expression of Arginase (EgArg) and Thioredoxin peroxidase (EgTPx) were quantified by Real-time PCR.

Results: A significant scolicidal activity of ABZ was observed only at a concentration of 800 μg/mL (100% PSCs mortality rate after 4 days of exposure), while the 200 and 400 μg/mL ABZ reached 100% PSCs mortality rate after 9 sequential days. The 400 μg/mL ABZ-β-CD had 100% scolicidal rate after 5 days of exposure. Morphological alterations using scanning electron microscopy in treated PSCs revealed that 400 μg/mL ABZ-β-CD induced higher Caspase-3 activity than their controls, indicating a more potent apoptotic outcome on the PSCs. Also, we showed that the 400 μg/mL ABZ-β-CD can down-regulate the mRNA expression of EgArg and EgTPx, indicating more potent interference with growth and antioxidant properties of PSCs.

Conclusions: In the present study, a significant scolicidal rate, apoptosis intensity and treatment efficacy was observed in PSCs treated with 400 μg/mL ABZ-β-CD compared to ABZ alone. This provides new insights into the use of nanostructured β-CD carriers with ABZ as a promising candidate to improve the treatment of CE in in vivo models.

Keywords: Albendazole; Apoptosis; Arginase; Echinococcus granulosus; Protoscoleces; Thioredoxin peroxidase; β-Cyclodextrin.

MeSH terms

Albendazole / pharmacology
Animals
Caspase 3
Dogs
Echinococcosis* / drug therapy
Echinococcus granulosus*
Humans
RNA, Messenger
beta-Cyclodextrins* / pharmacology

Substances

Albendazole
Caspase 3
beta-Cyclodextrins
RNA, Messenger