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

• Published in: European journal of pharmaceutics and biopharmaceutics 2014-11, Vol.88 (3), p.746-758
• Main Authors: Chirio, Daniela, Gallarate, Marina, Peira, Elena, Battaglia, Luigi, Muntoni, Elisabetta, Riganti, Chiara, Biasibetti, Elena, Capucchio, Maria Teresa, Valazza, Alberto, Panciani, Pierpaolo, Lanotte, Michele, Annovazzi, Laura, Caldera, Valentina, Mellai, Marta, Filice, Gaetano, Corona, Silvia, Schiffer, Davide
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents, Phytogenic - administration & dosage; Antineoplastic Agents, Phytogenic - pharmacokinetics; Antineoplastic Agents, Phytogenic - therapeutic use; BBB permeability; Blood-Brain Barrier - cytology; Blood-Brain Barrier - drug effects; Blood-Brain Barrier - metabolism; Brain Neoplasms - drug therapy; Brain Neoplasms - pathology; Cell Line, Tumor; Cell Membrane Permeability; Cell Survival - drug effects; Coacervation; Cytotoxicity; Dose-Response Relationship, Drug; Drug Carriers - chemistry; Drug Delivery Systems; Drug Liberation; Drug Stability; Glioblastoma; Glioblastoma - drug therapy; Glioblastoma - pathology; Humans; Lipids - chemistry; Nanoparticles - chemistry; Paclitaxel; Paclitaxel - administration & dosage; Paclitaxel - pharmacokinetics; Paclitaxel - therapeutic use; Particle Size; SLN; Surface Properties
• ISSN: 0939-6411; 1873-3441
• DOI: 10.1016/j.ejpb.2014.10.017

[Display omitted] 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 300–600nm 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 8–20mV 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 24h. 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.