a comparison of hepatocyte cytotoxic mechanisms for docetaxel and plga-docetaxel nanoparticls
نویسندگان
چکیده
docetaxel (dtx) is one of the most widely used drugs in oncology due to its high efficacy against several cancers. though, its routine clinical administration, formulated in tween 80, causes serious side effects. polylactide-co-glycolide (plga), biodegradable polyester synthesized and approved for human use, is employed to overcome this problem. in this investigation, we compare the cytotoxic mechanisms of dtx and plga-dtx in isolated rat hepatocytes. cytotoxicity of dtx and plga-dtx were associated with reactive oxygen species formation, activation of caspases cascade, collapse of mitochondrial membrane potential (mmp), lysosomal membrane leakiness and atp depletion. our results also showed that cyp2e1 is involved in the oxidative stress cytotoxicity mechanism and both drugs are detoxified via phase ii metabolic methylation. furthermore, we concluded that plga-dtx is bioactivated by gsh. it could also potentiate hepatocyte toxicity through a mitochondrial/lysosomal toxic cross-talk. in addition to these observed differences, it is likely that mode of hepatocyte membrane penetration is different between these compounds.
منابع مشابه
A Comparison of Hepatocyte Cytotoxic Mechanisms for Docetaxel and PLGA-Docetaxel Nanoparticls
Docetaxel (DTX) is one of the most widely used drugs in oncology due to its high efficacy against several cancers. Though, its routine clinical administration, formulated in tween 80, causes serious side effects. Polylactide-co-glycolide (PLGA), biodegradable polyester synthesized and approved for human use, is employed to overcome this problem. In this investigation, we compare the cytotoxic m...
متن کاملA Comparison of Hepatocyte Cytotoxic Mechanisms for Docetaxel and PLGA-Docetaxel Nanoparticls
Docetaxel (DTX) is one of the most widely used drugs in oncology due to its high efficacy against several cancers. Though, its routine clinical administration, formulated in tween 80, causes serious side effects. Polylactide-co-glycolide (PLGA), biodegradable polyester synthesized and approved for human use, is employed to overcome this problem. In this investigation, we compare the cytotoxic m...
متن کاملA Comparison of Hepatocyte Cytotoxic Mechanisms for Docetaxel and PLGA-Docetaxel Nanoparticls
Docetaxel (DTX) is one of the most widely used drugs in oncology due to its high efficacy against several cancers. Though, its routine clinical administration, formulated in tween 80, causes serious side effects. Polylactide-co-glycolide (PLGA), biodegradable polyester synthesized and approved for human use, is employed to overcome these problems. In this investigation, we compare the cytotoxic...
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Docetaxel-loaded PLGA and PLGA-PEG nanoparticles for intravenous application: pharmacokinetics and biodistribution profile
Docetaxel is a highly potent anticancer agent being used in a wide spectrum of cancer types. There are important matters of concern regarding the drug's pharmacokinetics related to the conventional formulation. Poly(lactide-co-glycolide) (PLGA) is a biocompatible/biodegradable polymer with variable physicochemical characteristics, and its application in human has been approved by the United Sta...
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عنوان ژورنال:
iranian journal of pharmaceutical researchجلد ۱۶، شماره ۱، صفحات ۲۴۹-۲۶۵
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