title: Formulation and in vitro evaluation of 17-allyamino-17-demethoxygeldanamycin (17-AAG) loaded polymeric mixed micelles for glioblastoma multiforme.
abstract: Glioblastoma multiforme (GBM) is the most common and aggressive malignant primary brain tumor in human. 17-Allylamino-17-demethoxy geldanamycin (17-AAG) is an inhibitor of heat shock protein 90 (HSP90). The highly lipophilic nature and selective targeting of tumor cells makes 17-AAG a promising candidate for therapy of GBMs but poor water solubility, short biological half-life and hepatotoxicity limited its clinical use. Polymeric mixed micelles composed of Pluronic® P-123 and F-127 (2:1 (w/w)) containing 17-AAG were prepared and characterized. Cellular uptake and in vitro cytotoxicity of the prepared micelles were determined in U87MG human glioblastoma cells. The particle size of 17-AAG loaded Pluronic(®) P-123 and F-127 mixed micelles was 22.2 ± 0.1 nm; drug loading was about 4.0 ± 0.5% (w/w) with 88.2 ± 3.1% (w/w) encapsulation efficiency. About 90% of drug was released from the nanoparticles over 8 days. Cellular uptake studies showed intracellular uptake of mixed micelles. Cytotoxicity study showed 5-fold increase (P < 0.05, n = 3) in the cytotoxicity of 17-AAG-loaded mixed micelles to free 17-AAG. Due to their targeting ability, size, high drug loading and controlled release behavior, 17-AAG loaded Pluronic(®) P-123 and F-127 mixed micelles might be developed as a delivery system for GBM treatment.
authors.affiliation: Department of Pharmaceutical Sciences, Irma Lerma Rangel College of Pharmacy, Texas A&M Health Science Center, Kingsville, TX 78363, USA.
authors.forename: Vipin
authors.initials: V
authors.lastname: Saxena
authors.forename: Muhammad Delwar
authors.initials: MD
authors.lastname: Hussain
mesh_terms: D016227:Benzoquinones / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001693:Biological Transport, Active; D001812:Blood-Brain Barrier; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding; D016503:Drug Delivery Systems; D005909:Glioblastoma / Q000188:drug therapy* / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors; D006801:Humans; D047029:Lactams, Macrocyclic / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008823:Micelles; D053769:Nanocapsules / Q000737:chemistry; D010316:Particle Size; D011060:Poloxalene / Q000737:chemistry; D020442:Poloxamer / Q000737:chemistry
chemical_list: D016227:Benzoquinones; D004337:Drug Carriers; D018841:HSP90 Heat-Shock Proteins; D047029:Lactams, Macrocyclic; D008823:Micelles; D053769:Nanocapsules; D020442:Poloxamer; C464484:pluronic block copolymer P123; C112765:tanespimycin; D011060:Poloxalene
keywords: 17-AAG; Glioblastoma multiforme; HSP90, Pluronic(®) P-123; Mixed micelles; Pluronic(®) F-127