In 2005, Kataoka and co-workers, in collaboration with NanoCarrier Co., Ltd. and Nippon Kayaku Co., Ltd., first reported on NK105, a paclitaxel-incorporated micelle formulation.99 The phase I clinical trial of NK105 first began in April 2004. Similar to NK911, the building block of NK105 is PEG-b-PAsp copolymers but with a slight modification to the aspartate blocks such that the carboxyl residues are converted into 4-phenyl-1-butanolate by an esterification reaction. The modification increases the hydrophobicity of the core-forming block that results in enhanced entrapment and retention of paclitaxel in the micelles. The resulting drug-loaded micelles contain 23% (w/w) paclitaxel with a weight-average diameter of approximately 85 nm.

With the improved micelle core stability, NK105 is predicted to act as a true drug carrier rather than a solubilizer. As indicated by the in vivo preclinical studies, NK105 is extremely stable in vivo with a 90-fold increase in the AUC and a 4-6-fold increase in the terminal phase half-life.99 In addition, the tumor AUC was found to be 25-times higher than that of Taxol®. The superior in vivo anti-tumor activity of NK105 in a human colorectal cancer xenograft model (HT-29) was a result of the enhanced drug accumulation in the tumor, allowing for more drug-loaded micelle-cell interactions. These results highlight the importance of polymer-drug compatibility and core stability in the design of effective micellar delivery systems. Therefore, the recent studies that focus on customizing copolymer compositions to accommodate the distinct properties of different drugs such as camptothecin,38,100 KRN 5500,60 and cisplatin101,102 may lead to the development of true polymeric micelle carriers for delivery to tumor tissues.

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