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Preparation, in vitro and in vivo evaluation of polymeric nanoparticles bas hyaluronic acid-poly(but
閱讀：238 發(fā)布時(shí)間：2015-4-13| 提 供 商 | 美國(guó)布魯克海文儀器公司 | 資料大小 | 227.5KB |
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Herein, we describe the preparation of a targeted cellular delivery system for morin hydrate (MH),
-molecular-weight hyaluronic acid-poly(butyl cyanoacrylate) (HA-PBCA) block copolymer. In ord
the therapeutic effect of MH, D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) was
HA-PBCA during the preparation process. The MH-loaded HA-PBCA “plain” nanoparticle (MH-P
PBCA/TPGS “mixed” nanoparticles (MH-MNs) were concomitantly characterized in terms of load
particle size, zeta potential, critical aggregation concentration, and morphology. The obtained MHMNs
exhibited a spherical morphology with a negative zeta potential and a particle size less than 2
favorable for drug targeting. Remarkably, the addition of TPGS resulted in about 1.6-fold increase
loading. The in vitro cell viability experiment revealed that MH-MNs enhanced the cytotoxicity of
cells compared with MH solution and MH-PNs. Furthermore, blank MNs containing TPGS exhibit
cytotoxic effects against cancer cells without diminishing the viability of normal cells. In addition,
uptake study indicated that MNs resulted in 2.28-fold higher cellular uptake than that of PNs, in A5
CD44 receptor competitive inhibition and the internalization pathway studies suggested that the int
mechanism of the nanoparticles was mediated mainly by the CD44 receptors through a clathrin-dep
endocytic pathway. More importantly, MH-MNs exhibited a higher in vivo antitumor potency and
tumor cell apoptosis than did MH-PNs, following intravenous administration to S180 tumor-bearin
Overall, the results imply that the developed nanoparticles are promising vehicles for the targeted d
lipophilic anticancer drugs.
Keywords: anti-tumor effect, hyaluronic acid, TPGS, morin hydrate, nanoparticles