title: Synthesis and evaluation of poly(styrene-co-maleic acid) micellar nanocarriers for the delivery of tanespimycin.
abstract: Polymeric micelles carrying the heat shock protein 90 inhibitor tanespimycin (17-N-allylamino-17-demethoxygeldanamycin) were synthesized using poly(styrene-co-maleic acid) (SMA) copolymers and evaluated in vitro and in vivo. SMA-tanespimycin micelles were prepared with a loading efficiency of 93%. The micelles incorporated 25.6% tanespimycin by weight, exhibited a mean diameter of 74 ± 7 nm by dynamic light scattering and a zeta potential of -35 ± 3 mV. Tanespimycin was released from the micelles in a controlled manner in vitro, with 62% released in 24h from a pH 7.4 buffer containing bovine serum albumin. The micellar drug delivery systems for tanespimycin showed potent activity against DU145 human prostate cancer cells, with an IC(50) of 230 nM. They further exhibited potent anti-cancer activity in vivo in nu/nu mice bearing subcutaneous DU145 human prostate cancer tumor xenografts, with significantly higher anticancer efficacy as measured by tumor regression when compared to free tanespimycin at an equivalent single dose of 10mg/kg. These data suggest further investigation of SMA-tanespimycin as a promising agent in the treatment of prostate cancer.
authors.affiliation: Department of Pharmaceutics and Pharmaceutical Chemistry, Salt Lake City, UT 84108, USA.
authors.forename: Nate
authors.initials: N
authors.lastname: Larson
authors.forename: Khaled
authors.initials: K
authors.lastname: Greish
authors.forename: Hillevi
authors.initials: H
authors.lastname: Bauer
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Maeda
authors.forename: Hamidreza
authors.initials: H
authors.lastname: Ghandehari
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry; D016227:Benzoquinones / Q000008:administration & dosage* / Q000737:chemistry; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D004339:Drug Compounding; D006801:Humans; D006863:Hydrogen-Ion Concentration; D020128:Inhibitory Concentration 50; D007279:Injections, Subcutaneous; D007700:Kinetics; D047029:Lactams, Macrocyclic / Q000008:administration & dosage* / Q000737:chemistry; D008027:Light; D008297:Male; D008298:Maleates / Q000138:chemical synthesis*; D051379:Mice; D008819:Mice, Nude; D008823:Micelles; D053758:Nanoparticles; D036103:Nanotechnology; D011137:Polystyrenes / Q000138:chemical synthesis*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D012542:Scattering, Radiation; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D016227:Benzoquinones; D004337:Drug Carriers; D047029:Lactams, Macrocyclic; D008298:Maleates; D008823:Micelles; D011137:Polystyrenes; C521900:poly(styrene-co-maleic anhydride); C112765:tanespimycin