Profiling in vivo release kinetics of drug nanocarriers is of high translational significance. However, this has remained unrealized due to the lack of direct methodologies to quantify either the total released or residual drugs. This study employed an indirect strategy, comparing pharmacokinetics and particokinetics, to estimate the in vivo release kinetics of paclitaxel (PTX) from intravenously administered mPEG-PDLLA polymeric micelles (PMs). Blood pharmacokinetics were profiled by chromatographically quantifying PTX, while particokinetics were determined following labeling PM particles by near-infrared fluorophores with aggregation-caused quenching properties. By monitoring the dynamic change in the PTX-to-copolymer ratio, the in vivo release of PTX from the PMs was estimated. The results revealed surprisingly rapid release, with over 88.2% and 99.0% of PTX released by 15 s and 5 min post-administration, respectively. It is concluded that PTX is released rapidly from PMs in vivo, and PMs may merely work as “solvents” to solubilize PTX rather than as carriers for targeted delivery.

Polymeric micelles  /  mPEG-PDLLA  /  Paclitaxel  /  Drug delivery  /  In vivo release  /  In vivo fate  /  Particokinetics  /  Pharmacokinetics