P51 PREPARATION OF ASIATIC ACID LOADED NANOPARTICLES FOR DELIVERY ACROSS THE BLOOD BRAIN BARRIER AND ITS EFFECTS ON GLIOBLASTOMA CELLS IN VITRO

• Published in: Neuro-oncology (Charlottesville, Va.) Vol. 16; no. suppl 6; p. vi8
• Main Authors: Thakor, Flourina, Welsby, Philip J, Wan, Ka-Wai, Welsby, Gail
• Format: Journal Article
• Language: English
• Published: 01.10.2014
• ISSN: 1522-8517
• DOI: 10.1093/neuonc/nou249.39

INTRODUCTION: Drug delivery across tight junctions of the blood brain barrier poses a significant challenge to glioma treatment. Biodegradable nanoparticles (NPs) formulated with poly- epsilon -caprolactone were prepared to investigate sustained delivery of asiatic acid (AA). METHOD: Blank & drug-loaded NPs were prepared by the solvent displacement method using a two-phase system consisting of acetone & water; drug (AA or cisplatin) was dissolved in the organic phase. NPs were characterised for stability, encapsulation efficiency, biodegradation & rate of drug release. The IC50 values for AA & cisplatin in SVGP12 and U87-MG cell lines were also established. RESULTS: Blank NPs were produced in the range of 131-148nm ( Day 0: 133 plus or minus 2; Day 60: 142 plus or minus 5), with AA- loaded particles in the range of 150-151nm ( Day 0: 153 plus or minus 3; Day 60: 150 plus or minus 1). NPs had a negative surface charge of -17 plus or minus 1 mV to -31 plus or minus 3 mV and -20 plus or minus 1 mV to -30 plus or minus 1 mV for blank & AA-loaded NPs, respectively. Polydispersity index was <1 demonstrating a monodisperse, uniform polymer was created. NPs were stable for a minimum of 60 days. AA-loaded NPs had a drug loading efficiency of 28 plus or minus 1.2%, showing a sustained drug release in phosphate buffered saline at pH 7.4 & pH 5.5 over 24hrs. An enhanced drug release of 65 plus or minus 4% at the end of 24hrs along with NP degradation was observed in the presence of lipase. The IC50 values for AA & cisplatin at 48hrs were 67mM & 10mM for SVGP12 and 50mM & 7mM for U87-MG cells respectively. CONCLUSION: This study provides a method for the preparation of stable, monodispersed NPs containing AA, showing a sustained drug release. Future work will examine the ability of the NPs to cross the blood brain barrier using an in vitro model system.