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Merck
  • 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
초록

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
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Sigma-Aldrich
Octadecylamine, technical grade, 90%
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Octadecylamine, ≥99.0% (GC)
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L-Ascorbic acid, tested according to Ph. Eur.
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L-Ascorbic acid, puriss. p.a., ≥99.0% (RT)
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Hydrogen chloride – methanol solution, ~1.25 m HCl (T), for GC derivatization, LiChropur
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L-Ascorbic acid, BioUltra, ≥99.5% (RT)
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Trypan Blue, Dye content 60 %, ≥80% (HPLC)
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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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Hydrogen chloride – ethanol solution, ~1.25 M HCl, for GC derivatization, LiChropur
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L-Ascorbic acid, ACS reagent, ≥99%
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Octadecylamine, ≥99% (GC)
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L-Ascorbic acid, 99%
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Cholesterol, tested according to Ph. Eur.
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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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Cholesterol, powder, BioReagent, suitable for cell culture, ≥99%
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Hydrocortisone, γ-irradiated, powder, BioXtra, suitable for cell culture
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Hydrocortisone, ≥98% (HPLC)
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Cholesterol, from sheep wool, ≥92.5% (GC), powder
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Hydrocortisone, BioReagent, suitable for cell culture
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Cholesterol, Sigma Grade, ≥99%
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L-Ascorbic acid, powder, suitable for cell culture, γ-irradiated
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L-Ascorbic acid, meets USP testing specifications
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Hydrochloric acid, 36.5-38.0%, BioReagent, for molecular biology
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L-Ascorbic acid, reagent grade, crystalline
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L-Ascorbic acid, reagent grade
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Trypan Blue, powder, BioReagent, suitable for cell culture
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Hydrochloric acid solution, volumetric, 0.1 M HCl (0.1N), endotoxin free
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Hydrochloric acid solution, 1.0 N, BioReagent, suitable for cell culture
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L-Ascorbic acid, BioXtra, ≥99.0%, crystalline