Encapsulation and controlled release of chemotherapeutic drugs by novel γ-cyclodextrin derived carriers.

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e13062 Background: Cyclodextrins (CDs) have the ability to carry drugs in their cavities. CD derivatives conjugated with a targeting moiety are expected to be drug carriers capable of targeting cancer cells with high specificity. In order to obtain effective drug carrier complexes, efficient methods for increasing the drug inclusion ability of the CD cavities are required. Methods: Nano-Carriers were prepared by chemical modification of γ-Cyclodextrin (γ-CD) and characterized using spectroscopic and chromatographic methods. We evaluated the effects of Doxorubicin (DOX) on cancer cell viability and drug uptake, under different in-vitro conditions: drug concentration, exposure time, exposure temperature, carrier types, drug/carrier ratio, and cell types. Human KB (ovarian carcinoma) or MCF-7 (breast carcinoma) cells were seeded into 96 well plates and treated with hyperthermia (41oC-55oC) for 2-10 minutes. Cell viability was determined by the MTT assay. To determine the intracellular drug uptake, tumor cells were seeded into 24 well plates and following incubation with DOX at different experimental conditions, we determined the DOX content of the exposed cells by HPLC and fluorimeter. Results: Chemical modifications of the native γCD's structure led to a more efficient encapsulation of DOX. γ-CD nano-carriers showed higher encapsulation ability than a-CD and b-CD based carriers. The cytotoxicity of DOX was significantly reduced by molecular encapsulation with our nano-carriers as indicated by the reduced intracellular DOX and the increased cell viability. The novel carriers induced a reduction of up to 97% in the uptake of DOX into KB and MCF-7 cells at 37oC. The degree of encapsulation and drug deactivation was dependent on drug concentration and carrier/drug molar ratio. Hyperthermia (41-45oC) clearly increased the intracellular drug uptake and therefore the potency of the encapsulated drug as compared to the effect at 37oC. Conclusions: This study indicates that γ-CD based nano-carriers may be a promising delivery system for specific targeting of chemotherapeutic drugs by their controlled release on the tumor site. This work is supported by an EU FP7 Industrial Academia Partnership Pathway IAPP.