Synthesis and Evaluation of Poly(Styrene-Co-Maleic Acid) Micellar Nanocarriers for the Delivery of Tanespimycin

Title
Synthesis and Evaluation of Poly(Styrene-Co-Maleic Acid) Micellar Nanocarriers for the Delivery of Tanespimycin
Authors
Nate LarsonKhaled GreishHillevi BauerHiroshi MaedaHamid Ghandehari
Keywords
Tanespimycin; 17-AAG; Polymeric micelle; Prostate cancer
Issue Date
2011-11
Publisher
International journal of pharmaceutics
Citation
VOL 420, NO 1, 111-117
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 24 h 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 IC50 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 10 mg/kg. These data suggest further investigation of SMA-tanespimycin as a promising agent in the treatment of prostate cancer.
URI
http://pubs.kist.re.kr/handle/201004/43789
ISSN
03785173
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KIST Publication > Article
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