Purpose. Develop a Cremophor® and solvent free formulation of paclitaxel using amphiphilic block co-polymer micelles of poly(ethylene glycol)-b-poly(ε-caprolactone) (PEG-b-PCL) and characterize their release, solubility, cytotoxicity, tolerability, and disposition. Methods. Hydrophobic prodrugs of paclitaxel were synthesized via DCC/DMAP or anhydride chemistry to overcome the poor loading (<1% w/w) of paclitaxel in micelles of PEG-b-PCL. Micelles were prepared by a co-solvent extraction technique. A micellar formulation of paclitaxel prodrug (PAX7′C6) was dosed intravenously to rats (10 mg/kg) and compared to Taxol® (paclitaxel in CrEL:EtOH) and PAX7′C6 in CrEL:EtOH as controls at the same dose. Pharmacokinetic parameters and tissue distribution were assessed. Results. Paclitaxel prodrugs had solubilities >5 mg/ml in PEG-b-PCL micelles. Resulting PEG-b-PCL micelles contained 17-22% w/w prodrug and were less than 50 nm in diameter. PEG-b-PCL micelles released paclitaxel prodrugs over several days, t1/2>3 d. Only the 7′derivative of paclitaxel with the shortest acylchain 7′hexonoate (PAX7′C6) maintained cytotoxic activity similar to unmodified paclitaxel. PAX7′C6 micelles demonstrated an increase in area under the curve, half-life, and mean residence time while total clearance and volume of distribution decreased. Conclusions. Paclitaxel prodrugs in PEG-b-PCL micelle nanocarriers augment the disposition and increase tolerability making further studies on tumor efficacy warranted. © 2007 Springer Science+Business Media, LLC.