Nanoscale polymeric
micelles have promising applications as drug delivery systems (DDS). In this work, to improve the anti-
tumor activity and eliminate toxicity of the commercial formulation (
cremophor EL and
ethanol) of
paclitaxel (PTX), we developed biodegradable poly(
ethylene glycol)-poly(ε-
caprolactone) (
MPEG-PCL)
micelles entrapping PTX by a simple one-step solid dispersion method, which is without any
surfactants or additives and is easy to scale up. In addition, the PTX
micelles could be lyophilized into
powder without any adjuvant and the re-dissolved PTX
micelles are stable and homogeneous. The prepared PTX
micelles have a mean particle size of 38.06 ± 2.30 nm, a polydispersity index of 0.168 ± 0.014, a
drug loading of 14.89 ± 0.06% and an encapsulation efficiency of 99.25 ± 0.38%. A molecular modeling study implied that PTX interacted with PCL as a core, which was embraced by PEG as a shell. The encapsulation of PTX in polymeric
micelles enhanced its cytotoxicity by increasing the uptake by LL/2 cells. A sustained in vitro release behavior and slow extravasation behavior from blood vessels in a transgenic zebrafish model were observed in the PTX
micelles. Furthermore, compared with Taxol®, the PTX
micelles were more effective in suppressing
tumor growth in the subcutaneous LL/2
tumor model. The PTX
micelles also inhibited
metastases in the pulmonary metastatic LL/2
tumor model and prolonged survival in both mouse models. Pharmacokinetic and tissue distribution studies showed that after PTX was encapsulated in polymeric
micelles, the biodistribution pattern of PTX was altered and the PTX concentration in
tumors was increased compared with Taxol® after
intravenous injection. In conclusion, we have developed a polymeric
micelles entrapping PTX that enhanced cytotoxicity in vitro and improved anti-
tumor activity in vivo with low systemic toxicity on pulmonary
carcinoma. The biodegradable
MPEG-PCL micelles entrapping PTX may have promising applications in pulmonary
carcinoma therapy.