Stable and efficient delivery of docetaxel by micelle-encapsulation using a tripodal cyclotriphosphazene amphiphile

Docetaxel micelle-encapsulated by a tripodal cyclotriphosphazene amphiphilile [NP(PEG750)(GlyPheLeu) ₂Et] ₃ (CP750) exhibited outstanding drug-loaded micelle stability in aqueous solution compared with the polymeric micelles assembled from linear block copolymers. Furthermore, docetaxel micelle-encapsulated by CP750 is obtainable in solvent free powder form, which is immediately soluble in any aqueous media including saline and PBS and very stable to photo-degradation even in the room light at room temperature. Although docetaxel micelle-encapsulated by CP750 did not display highly improved pharmacokinetic profile compared with Taxotere® currently in clinical use, its in vivo xenograft trials exhibited excellent antitumor efficacy by showing complete tumor regression against the breast cancer cells (MDA-MB-231) at a lower dose of 5 mg/kg and better efficacy against gastric cancer cells (MKN-28) compared with Taxotere®. Furthermore, according to the comparative acute toxicity study, toxicities associated with Taxotere® may be remarkably reduced by micelle-encapsulation of docetaxel using CP750, which afforded a much higher LD ₅₀ value of 75 mg/kg compared with 28 mg/kg of docetaxel in Taxotere®. Thus docetaxel micelle-encapsulated by CP750 has entered the stage of preclinical studies.