Doxorubicin

Doxorubicin (Adriamycin®), a member of the anthracycline antibiotics family, is currently employed for treatment of many types of cancer because of its broad anti-tumor spectrum. It is approved, either alone or in combination with other chemotherapeutic drugs, for treatment of breast, ovarian, bladder, lung, thyroid, and gastric cancer as well as malignant lymphoma, acute forms of leukemia, and sarcomas.74 The cytotoxic effect of doxorubicin is said to result from a combination of cell damage mechanisms, some that have not been conclusively identified. One of the effects of doxorubicin that is known to contribute to its anti-tumor activity is the inhibition of cellular replication and DNA transcription as a result of an irreversible change in the DNA tertiary structure.75 This non-cell type specific cytotoxic effect of doxorubicin is mainly attributed to its ability to intercalate between DNA base pairs with its planar structure (Figure 17.3a). Indeed, the planar moiety of doxorubicin has been shown to improve the stability of micelles when loaded in the micelle core.76 Doxorubicin has been successfully loaded into micelles formed from PEG-b-poly(s-caprolactone) (PEG-b-PCL),41 PEG-b-poly(D,L-lactide-co-glycolide) (PEG-b-PLGA),77,78 PEG-b-poly(propylene oxide)-b-PEG (PEG-b-PPO-b-PEG; Pluronic®),26,79-81 and PEG-b-poly

16 32 82 83

(aspartic acid) (PEG-b-PAsp).16,32,82,83 Currently, two doxorubicin-loaded micelle formulations, NK911 (i.e., PEG-b-PAsp) and SP1049C (i.e., Pluronic®) are being investigated in clinical trials.

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