Original ArticleOptimizing particle size of docetaxel-loaded micelles for enhanced treatment of oral epidermoid carcinoma

Understanding how the size of nanocarriers affects their fate in biological systems in vivo is of fundamental importance for rational design of drug delivery systems. In this study, five docetaxel (DTX)-loaded methoxy poly(ethylene glycol)-poly(lactide) micelles of different sizes (30-230 nm) were prepared. It was observed that the permeation of micelles within both the multicellular tumor spheroids and tumor xenografts in mice was dependent on the size of the micelle. In addition, the size of micelles influenced their pharmacokinetic behavior. DTX-loaded pH-sensitive micelle based on poly(ethylene glycol)-poly(lactide)-poly(β-amino ester) (DTX-pHPM) was constructed to further illustrate the effect of particle size. As expected, DTX-pHPM improved tumor penetration, uptake by tumor cells, and prolonged circulation time, consequently demonstrating the highest inhibition of in vivo tumor growth (84.4%) in oral epidermoid carcinoma. Taken together, our findings can aid in designing nano-scale drug delivery systems for cancer therapy by optimizing the particle size.

Graphical AbstractFive micelles (30-230 nm) based on methoxy poly(ethylene glycol)-poly(lactide) copolymers and one size/charge-changing micelle based on amphiphilic poly(β-amino ester) derivates were prepared for the investigation of size effects. Through rational design of the particle size, an optimal micellar formulation of docetaxel with prolonged circulation time, improved intratumoral penetration, and enhanced cellular uptake was obtained to impede the tumor growth effectively.90