Positive-charged solid lipid nanoparticles as paclitaxel drug delivery system in gliohlastoma treatment

被引:73
作者
Chirio, Daniela [1 ]
Gallarate, Marina [1 ]
Peira, Elena [1 ]
Battaglia, Luigi [1 ]
Muntoni, Elisabetta [1 ]
Riganti, Chiara [2 ]
Biasibetti, Elena [3 ]
Capucchio, Maria Teresa [3 ]
Valazza, Alberto [3 ]
Panciani, Pierpaolo [4 ]
Lanotte, Michele [4 ]
Annovazzi, Laura [5 ]
Caldera, Valentina [5 ]
Mellai, Marta [5 ]
Filice, Gaetano [6 ]
Corona, Silvia [6 ]
Schiffer, Davide [5 ]
机构
[1] Univ Turin, Dipartimento Sci & Tecnol Farmaco, I-10125 Turin, Italy
[2] Univ Turin, Dipartimento Oncol, Orbassano, TO, Italy
[3] Univ Turin, Dipartimento Sci Vet, Grugliasco, TO, Italy
[4] Univ Turin, Dipartimento Neurosci, I-10125 Turin, Italy
[5] Policlin Monza, Ctr NeuroBioOncol, Vercelli, Italy
[6] Univ Pavia, IRCCS Policlin San Matteo, Dipartimento Malattie Infett, I-27100 Pavia, Italy
关键词
Paclitaxel; SLN; Coacervation; BBB permeability; Cytotoxicity; Glioblastoma; BLOOD-BRAIN-BARRIER; STEM-LIKE CELLS; IN-VITRO; P-GLYCOPROTEIN; DOXORUBICIN; RESISTANCE; PERMEABILITY; FORMULATION; TRANSPORT; TUMORS;
D O I
10.1016/j.ejpb.2014.10.017
中图分类号
R9 [药学];
学科分类号
100702 [药剂学];
摘要
Paclitaxel loaded solid lipid nanoparticles (SLN) of behenic acid were prepared with the coacervation technique. Generally, spherical shaped SLN with mean diameters in the range 300-600 nm were obtained. The introduction of charged molecules, such as stearylamine and glycol chitosan into the formulation allowed to obtain positive SLN with Zeta potential in the 8-20 mV range and encapsulation efficiency in the 25-90% range. Blood-brain barrier (BBB) permeability, tested in vitro through hCMEC/D3 cells monolayer, showed a significantly increase in the permeation of Coumarin-6, used as model drug, when vehicled in SLN. Positive-charged SLN do not seem to enhance permeation although stearylamine-positive SLN resulted the best permeable formulation after 24 h. Cytotoxicity studies on NO3 glioblastoma cell line demonstrated the maintenance of cytotoxic activity of all paclitaxel-loaded SLN that was always unmodified or greater compared with free drug. No difference in cytotoxicity was noted between neutral and charged SLN. Co-culture experiments with hCMEC/D3 and different glioblastoma cells evidenced that, when delivered in SLN, paclitaxel increased its cytotoxicity towards glioblastoma cells. (C) 2014 Elsevier B.V. All rights reserved.
引用
收藏
页码:746 / 758
页数:13
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