Journal
JOURNAL OF MATERIALS CHEMISTRY B
Volume 2, Issue 38, Pages 6534-6548Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/C4TB00499J
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Funding
- National Natural Science Foundation of China [51373142]
- Scientific and Technical Project of Fujian Province of China [2009J1009]
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In the present study we have investigated novel MTX prodrug-targeted and MMC-loaded PLA-lipid-PEG hybrid NPs. These employ a double emulsion solvent evaporation method for the introduction of an anticancer drugs moiety of the MMC-soybean phosphatidylcholine complex or DSPE-PEG-MTX, in which the MTX prodrug can be exploited as a targeting ligand. The prepared drug delivery systems present a spherical shape, a small particle size (219.6 +/- 2.1 nm) with narrow particle size distribution, high MMC encapsulation efficiency (90.5 +/- 3.0%) and a sustained and pH-controlled MMC release. The advantage of the new drug delivery systems is that the two-anticancer drug moiety can coordinate the early-phase targeting effect with the later-phase anticancer effect. In vivo pharmacokinetics, following intravenous administration of the drug delivery systems, indicates a prolonged systemic circulation time of MMC. More importantly, the drug delivery systems exhibited a significant accumulation of MMC in the nuclei as the site of MMC action, which was indicative of the enhancement of anticancer activity. Such a design of drug delivery systems may open up a new horizon for targeted delivery and sustained and controlled release of MMC.
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