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  • Positive-charged solid lipid nanoparticles as paclitaxel drug delivery system in glioblastoma treatment.

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

European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V (2014-12-03)
Daniela Chirio, Marina Gallarate, Elena Peira, Luigi Battaglia, Elisabetta Muntoni, Chiara Riganti, Elena Biasibetti, Maria Teresa Capucchio, Alberto Valazza, Pierpaolo Panciani, Michele Lanotte, Laura Annovazzi, Valentina Caldera, Marta Mellai, Gaetano Filice, Silvia Corona, Davide Schiffer
ABSTRACT

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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Octadecylamine, technical grade, 90%
Supelco
Hydrogen chloride – 2-propanol solution, ~1.25 M HCl (T), for GC derivatization, LiChropur
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Sodium dodecyl sulfate, BioUltra, for molecular biology, ≥99.0% (GC)
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Hydrochloric acid solution, ~6 M in H2O, for amino acid analysis
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Hydrogen chloride – methanol solution, ~1.25 m HCl (T), for GC derivatization, LiChropur
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L-Ascorbic acid, puriss. p.a., ACS reagent, reag. ISO, Ph. Eur., 99.7-100.5% (oxidimetric)
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Methanol, analytical standard
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Sodium dodecyl sulfate, suitable for ion pair chromatography, LiChropur, ≥99.0%
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SyntheChol® NS0 Supplement, 500 ×, synthetic cholesterol, animal component-free, aqueous solution, sterile-filtered, suitable for cell culture
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Cholesterol solution, certified reference material, 10 mg/mL in chloroform
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Sodium phosphate monobasic-16O4, 99.9 atom % 16O
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Ethanol solution, certified reference material, 2000 μg/mL in methanol
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Sodium dodecyl sulfate, ACS reagent, ≥99.0%
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L-Ascorbic acid, ACS reagent, ≥99%
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L-Ascorbic acid, BioUltra, ≥99.5% (RT)
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Octadecylamine, ≥99.0% (GC)
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Sodium hydroxide, BioUltra, for luminescence, ≥98.0% (T), pellets
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Sodium hydroxide solution, BioUltra, for molecular biology, 10 M in H2O
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L-Ascorbic acid, 99%
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Hydrogen chloride – ethanol solution, ~1.25 M HCl, for GC derivatization, LiChropur
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Methanol, anhydrous, 99.8%
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3-Ethyl-2,4-pentanedione, mixture of tautomers, 98%
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Octadecylamine, ≥99% (GC)
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Trypan Blue, Dye content 60 %, ≥80% (HPLC)
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L-Ascorbic acid, meets USP testing specifications
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