Similar to doxorubicin, paclitaxel is a chemotherapeutic drug that has been loaded into block copolymer micelles for investigation in clinical trials. Paclitaxel is an anti-neoplastic drug that was first extracted from the bark of Pacific yew trees (Figure 17.3b). The cytotoxic effect of paclitaxel is mainly attributed to its ability to promote the assembly as well as prevent the depo-lymerization of microtubules.87 Stabilization of the microtubule networks inhibits normal interphase and mitotic functions that, in turn, impedes cell division. Paclitaxel is approved for treatment of ovarian, breast, and non-small cell lung cancers as well as AIDS-related Kaposi's sarcoma.87 Paclitaxel is highly hydrophobic with a log P value of 3.96 and low aqueous solubility of 1 mg/mL.88,89 The commercialized formulation of paclitaxel, known as Taxol®, contains the drug dissolved in a mixture of Cremophor EL and ethanol that increases its solubility by more than 6000-fold. However, administration of Cremophor EL leads to severe dose-limiting toxicities such as hypersensitivity reactions and neuropathy.90 As a result, much effort has gone into the development of a novel formulation of paclitaxel using biocompatible and biodegradable polymeric micelles. Paclitaxel has been successfully loaded into PEG-b-poly(D,L-lactide) (PEG-b-PDLLA),35,37,90,91 poly(N-vinyl-pyrrolidone)-b-PDLLA (PVP-b-PDLLA),28,92 PEG-b-PCL,93-95 and PEG-b-poly(S-valerolactone) (PEG-b-PVL).95 Genexol-PM (i.e., PEG-b-PDLLA) and NK105 (i.e., PEG-b-PAsp) represent two paclitaxel-loaded polymeric micelle formulations that have entered clinical trial development.

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