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

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.

• Authors: 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
• Journal: European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V (Eur J Pharm Biopharm) Vol. 88 Issue 3 Pg. 746-58 (Nov 2014) ISSN: 1873-3441 [Electronic] Netherlands
• PMID: 25445304 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents, Phytogenic
• Drug Carriers
• Lipids
• Paclitaxel

Topics

• Antineoplastic Agents, Phytogenic (administration & dosage, pharmacokinetics, therapeutic use)
• Blood-Brain Barrier (cytology, drug effects, metabolism)
• Brain Neoplasms (drug therapy, pathology)
• Cell Line, Tumor
• Cell Membrane Permeability
• Cell Survival (drug effects)
• Dose-Response Relationship, Drug
• Drug Carriers (chemistry)
• Drug Delivery Systems
• Drug Liberation
• Drug Stability
• Glioblastoma (drug therapy, pathology)
• Humans
• Lipids (chemistry)
• Nanoparticles (chemistry)
• Paclitaxel (administration & dosage, pharmacokinetics, therapeutic use)
• Particle Size
• Surface Properties