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Pharm Res. 2008 Aug;25(8):1925-35. doi: 10.1007/s11095-008-9611-6. Epub 2008 May 29.

In vitro and in vivo investigation on PLA-TPGS nanoparticles for controlled and sustained small molecule chemotherapy.

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Department of Chemical and Biomolecular Engineering, National University of Singapore, Block E5, 02-11, 4 Engineering Drive 4, Kent Ridge, 117576, Singapore.



The aim of this work was to evaluate in vivo poly(lactide)-D: -alpha-tocopheryl polyethylene glycol 1,000 succinate nanoparticles (PLA-TPGS NPs) for controlled and sustained small molecule drug chemotherapy.


The drug-loaded PLA-TPGS NPs were prepared by the dialysis method. Particle size, surface morphology and surface chemistry, in vitro drug release and cellular uptake of NPs were characterized. In vitro and in vivo therapeutic effects of the nanoparticle formulation were evaluated in comparison with Taxol.


The PLA-TPGS NP formulation exhibited significant advantages in in vivo pharmacokinetics and xenograft tumor model versus the PLGA NP formulation and the pristine drug. Compared with Taxol, the PLA-TPGS NP formulation achieved 27.4-fold longer half-life in circulation, 1.6-fold larger area-under-the-curve (AUC) with no portion located above the maximum tolerance concentration level. For the first time in the literature, one shot for 240 h chemotherapy was achieved in comparison with only 22 h chemotherapy for Taxol at the same 10 mg/kg paclitaxel dose. Xenograft tumor model further confirmed the advantages of the NP formulation versus Taxol.


The PLA-TPGS NP formulation can realize a way of controlled and sustained drug release for more than 10 days, which relieves one of the two major concerns on cancer nanotechnology, i.e. feasibility.

[Indexed for MEDLINE]

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