Proapoptotic miltefosine nanovesicles show synergism with paclitaxel: Implications for glioblastoma multiforme therapy

Highlights • Miltefosine based proapoptotic lipid nanovesicles encapsulate paclitaxel with high efficiency. • Nanovesicles while exhibiting sustained release of paclitaxel in nasal fluid, show triggered release profile in cerebrospinal fluid. • Nanovesicles result in synergistic cytotoxic effect of...

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Veröffentlicht in:	Cancer letters 2013-07, Vol.334 (2), p.274-283
Hauptverfasser:	Thakur, Ankita, Joshi, Nitin, Shanmugam, Thanigaivel, Banerjee, Rinti
Format:	Artikel
Sprache:	eng
Schlagworte:	Animals anticarcinogenic activity Antineoplastic Combined Chemotherapy Protocols - pharmacokinetics Antineoplastic Combined Chemotherapy Protocols - pharmacology apoptosis Blood brain barrier Blood-Brain Barrier - metabolism brain Brain Neoplasms - drug therapy Brain Neoplasms - pathology Cancer Cell Line, Tumor cerebrospinal fluid clathrin Drug delivery systems Drug Synergism Drug therapy encapsulation Female gene overexpression genes Glioblastoma - drug therapy Glioblastoma - metabolism Glioblastoma - pathology Glioblastoma multiforme Hematology, Oncology and Palliative Medicine Humans Intranasal intranasal administration Kinases Lipid nanovesicles Male Miltefosine multiple drug resistance Nanostructures - administration & dosage Nanostructures - chemistry Nose Paclitaxel Paclitaxel - administration & dosage Paclitaxel - chemistry Paclitaxel - pharmacokinetics Paclitaxel - pharmacology Phosphorylcholine - administration & dosage Phosphorylcholine - analogs & derivatives Phosphorylcholine - chemistry Phosphorylcholine - pharmacokinetics Phosphorylcholine - pharmacology Rats Rats, Wistar synergism therapeutics zeta potential
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Zusammenfassung:	Highlights • Miltefosine based proapoptotic lipid nanovesicles encapsulate paclitaxel with high efficiency. • Nanovesicles while exhibiting sustained release of paclitaxel in nasal fluid, show triggered release profile in cerebrospinal fluid. • Nanovesicles result in synergistic cytotoxic effect of paclitaxel and miltefosine and overcome drug resistance in glioblastoma cells, U-87 MG. • ATP dependent endocytosis of nanovesicles by U-87 MG cells via clathrin mediated pathway. • Upon intranasal administration, nanovesicles reach brain and are also able to cross blood brain barrier upon intravenous administration.
ISSN:	0304-3835 1872-7980
DOI:	10.1016/j.canlet.2012.08.022