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Evaluation Of Toxicity And Antitumour Effects Of A Hydroxypropyl ?-Cyclodextrin Inclusion Complex Of Quercetin

Author(s): M. A Indap, Sunita C Bhosle, P. T Tayade, P. R Vavia

The general toxicity and antineoplastic activity of a hydroxypropyl beta cyclodextrin complex were investigated recently by us. Complexed quercetin at the large lethal dose of 400 mg/kg was not found to be toxic. (Free quercetin can be administered only at smaller doses because of its poor aqueous solubility). The maximum tolerated dose corresponding to the LD10 was > 400 mg/kg for hydroxypropyl beta cyclodextrin complex of quercetin obtained after a single intraperitoneal application which proved to be less toxic than quercetin. In vitro experiments have shown that hydroxypropyl beta cyclodextrin complex of quercetin induces apoptosis in both K-562 and B16F10 melanoma cells. Therapeutic experiments in C3H/J mice implanted with mammary adenocarcinoma cells resulted in significantly increased effectiveness of hydroxypropyl beta cyclodextrin complex of quercetin compared to free quercetin. We observed no apparent toxicity to bone marrow of irradiated Swiss mice previously administered hydroxypropyl beta cyclodextrin complex of quercetin for a week. This suggest that hydroxypropyl beta cyclodextrin complex was able to protect bone marrow cells from lethal effect of radiation. When the cytotoxicities of quercetin and its complexes were compared on erythrocytes of rat and rabbits, no significant differences were observed. The ability to selectively target quercetin via its cyclodextrin inclusion complex against cancer growth could improve the therapeutic effectiveness of cyclodextrin preparations as well as reduce adverse side effects associated with quercetin. The new cyclodextrin inclusion complex appears to have high potential for the treatment of leukemias and possibly also for solid tumors.


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