Drug formulation by ligand conjugated nanoparticles of biodegradable polymers has
become one of the most important strategies in drug targeting. We have developed in
our previous work nanoparticles of a mixture of two vitamin E TPGS based copolymers
PLA-TPGS and TPGS-TOOH with the latter for Herceptin conjugation for targeted delivery
of anticancer drugs such as docetaxel to the cancer cells of human epidermal growth
factor receptor 2 (HER2) overexpression. In this research, we investigated the effects
of the PEG chain length in TPGS, which is in fact a PEGylated vitamin E, on the cellular
uptake and cytotoxicity of the drug formulated in the Herceptin-conjugated nanoparticles
of PLA-TPGS/TPGS-COOH blend (NPs). Such NPs of PEG1000, PEG2000, PEG3350 and PEG5000,
i.e. the PEG of molecule weight 1000, 2000, 3350 and 5000, were prepared by the nanoprecipitation
method and characterized for their size and size distribution, drug loading, surface
morphology, surface charge and surface chemistry as well as in vitro drug release
profile, cellular uptake and cytotoxicity. We found among such nanoparticles, those
of PEG1000, i.e. of the shortest PEG tethering chain length, could result in the best
therapeutic effects, which are 24.1%, 37.3%, 38.1% more efficient in cellular uptake
and 68.1%, 90%, 92.6% lower in IC50 (thus higher in cytotoxicity) than the Herceptin-conjugated
nanoparticles of PLA-TPGS/TPGS-COOH blend of PEG2000, PEG3350 and PEG5000 respectively
in treatment of SK-BR-3 cancer cells which are of high HER2 overexpression. We provided
a theoretical explanation from surface mechanics and thermodynamics for endocytosis
of nanoparticles.
Copyright © 2014 Elsevier Ltd. All rights reserved.