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Scolicidal and apoptotic activities of albendazole sulfoxide and albendazole sulfoxide-loaded PLGA-PEG as a novel nanopolymeric particle against Echinococcus granulosus protoscoleces.

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تاریخ
2016
نویسنده
Naseri, M
Akbarzadeh, A
Spotin, A
Akbari, NA
Mahami-Oskouei, M
Ahmadpour, E
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نمایش پرونده کامل آیتم
چکیده
Treatment failures of human cystic echinococcosis (CE) with albendazole (ABZ) have attributed to its low solubility and poor drug absorption rate, resulting in low drug level in plasma. The scolicidal effects of ABZ-loaded liposome nanoparticles have recently evaluated; however, these particles have several challenges due to their low encapsulated load. This investigation was designed to evaluate and compare in vitro apoptotic activities of ABZ sulfoxide (ABZs) and ABZs-loaded poly(lactic-co-glycolic acid) (PLGA)-PEG against protoscoleces (PSCs). ABZs-loaded PLGA-PEG was prepared by a double-emulsion method (W1/O/W2). Various concentrations of ABZs and ABZs-loaded PLGA-PEG (50, 100, 150, and 200آ ?g/ml) were experimentally tested against PSC of CE at different exposure times (5, 10, 20, 30, and 60آ min). ABZs-loaded PLGA-PEG at concentrations of 150 and 200آ ?g/ml was able to act at a 100آ % scolicidal rate in all exposure times (5 to 60آ min), while ABZs at a concentration of 200آ ?g/ml demonstrated 94, 100, and 100آ % mortality rates following 20, 30, and 60آ min of exposure times, respectively. The messenger RNA (mRNA) expression of caspase-3 was assessed by semi-quantitative RT-PCR after 15آ h of exposure. Caspase-3 mRNA expression was higher in both PSC treated with ABZs and PSC treated with ABZs-loaded PLGA-PEG than that in control groups (P?<?0.05). No significant difference was observed between the apoptotic intensity of PSC treated with ABZs and that of PSC treated with ABZs-loaded PLGA-PEG (P?>?0.05). DNA fragmentation assay and ultrastructural changes revealed that ABZs and ABZs-loaded PLGA-PEG induced the apoptosis of PSC by activation of caspase-3. The higher permeability and scolicidal rate of ABZs-loaded PLGA-PEG can be addressed as an effectual alternative strategy to improve the treatment of human CE.
URI
http://dspace.tbzmed.ac.ir:8080/xmlui/handle/123456789/39670
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