Studies on anticancer activity of 17-AAG poly-butylcyanoacrylate nanoparticles

doi:10.3969/j.issn.1006-7795.2015.02.005

Journal of Capital Medical University ›› 2015, Vol. 36 ›› Issue (2): 178-184.doi: 10.3969/j.issn.1006-7795.2015.02.005

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Studies on anticancer activity of 17-AAG poly-butylcyanoacrylate nanoparticles

Yan Yan¹, Wang Yuji², Wu Jianhui², Cui Chunying¹

1. Department of Pharmaceutics, School of Chemical Biology and Pharmaceutical Sciences, Capital Medical University, Beijing 100069, China;
2. Department of Medicinal Chemistry, School of Chemical Biology and Pharmaceutical Sciences, Capital Medical University, Beijing 100069, China

Received:2014-12-08 Online:2015-04-21 Published:2015-04-16
Supported by:
This study was supported by Significant New Drugs Creation "Five-year" Plan Special Science and Technology Major(2011ZX09302-007-01).

Abstract

Abstract: Objective To prepare 17-allylamino-17-demethoxygeldana-mycin poly-butylcyanoacrylate nanoparticles(17-AAG-PBCA-NPs) and study the anticancer activity of 17-AAG poly-butylcyanoacrylate nanoparticles. Methods 17-AAG was encapsulated in PBCA-NPs by interfacial polymerization method. Using single factor analysis combined with orthogonal design to compare the effect factors on 17-AAG-PBCA-NPs, optimizing the preparation method of 17-AAG-PBCA-NPs. Nanoparticle size analyzer, TEM and SEM were used to identify and analyze the characteristics of 17-AAG-PBCA-NPs. The dynamic dialysis method was used to determine the in vitro release of 17-AAG-PBCA-NPs. Results Optimal dosage of drug mass ratio was 1∶10. The conditions of the reaction system were: pH 2, 1 200 r/min, F-68, 3% Dextran70. The time of polymerization was 3 hours. The optimal encapsulation efficiency was more than 90%. The morphology of 17-AAG-PBCA-NPs was spherical shape with (180.5±12.0) nm in diameter and the Zeta potential ranged from -20 to -30 mV. The release of 17-AAG-PBCA-NPs in vitro was determined by dynamic dialysis method and it has been shown that the release of drug from the PBCA-NPs exhibited a rapid burst release followed by a sustained release. 17-AAG-PBCA-NPs showed good stability in plasma. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT) assay of the 17-AAG-PBCA-NPs and 17-AAG using HepG2, A375, HeLa, MCF-7 and SHSY5Y cell line showed that the 17-AAG-PBCA-NPs and 17-AAG inhibited the growth of HepG2, A375, HeLa, MCF-7 and SHSY5Y cells, showing a time-dependent manner, respectively. Furthermore, in vivo anti-tumor activity of 17-AAG-PBCA-NPs was evaluated in sarcoma bearing mice following intraperitoneal injection. Compared with 17-AAG, 17-AAG-PBCA-NPs achieved superior sustained-release effect, and extended the dosing interval further, increased tolerated dose, reduced the side effect of the drug, and improved the compliance to medication, safety and medication. Conclusion 17-AAG-PBCA-NPs were prepared by using interfacial polymerization method. Further optimization of the preparation method is both beneficial to the characteristic and sustained release effect of 17-AAG-PBCA-NPs.

Key words: 17-allylamino-17-demethoxygeldanamycin(17-AAG), poly-butylcyanoacrylate, antitumor

CLC Number:

R965.1

Yan Yan, Wang Yuji, Wu Jianhui, Cui Chunying. Studies on anticancer activity of 17-AAG poly-butylcyanoacrylate nanoparticles[J]. Journal of Capital Medical University, 2015, 36(2): 178-184.

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References

[1] Whitesell L, Lindquist S L. HSP90 and the chaperoning of cancer[J]. Na Rev Cancer, 2005,5(10):761-772.
[2] Sauvageot C M, Weatherbee J L, Kesari S, et al. Efficacy of the HSP90 inhibitor 17-AAG in human glioma cell lines and tumorigenic glioma stem cells[J]. Neuro Oncol, 2009,11(2):109-121.
[3] Önyüksel H, Mohanty P S, Rubinstein I. VIP-grafted sterically stabilized phospholipid nanomicellar 17-allylamino-17-demethoxy geldanamycin:a novel targeted nanomedicine for breast cancer[J]. Int J Pharm, 2009,365(1):157-161.
[4] Yordanov G, Evangelatov A, Skrobanska R. Epirubicin loaded to pre-polymerized poly(butyl-cyanoacrylate) nanoparticles:Preparation and in vitro evaluation in human lung adenocarcinoma cells[J]. Colloids Surf B Biointerfaces, 2013,107:115-123.
[5] Reddy L H, Murthy R S R. Pharmacokinetics and biodistribution studies of doxorubicin loaded poly(butyl-cyanoacrylate) nanoparticles synthesized by two different techniques[J]. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub, 2004,148(2):161-166.
[6] Hu Y, Jiang X, Ding Y, et al. Preparation and drug release behaviors of nimodipine-loaded poly(caprolactone)-poly(ethylene oxide)-polylactide amphiphilic copolymer nanoparticles[J]. Biomaterials, 2003,24(13):2395-2404.
[7] Zhang Y, Zhang Y, Chen J, et al. Polybutylcyanoacrylate nanoparticles as novel vectors in cancer gene therapy[J]. Nanomedicine, 2007,3(2):144-153.
[8] Mulik R, Mahadik K, Paradkar A. Development of curcuminoids loaded poly(butyl) cyanoacrylate nanoparticles:physicochemical characterization and stability study[J]. Eur J Pharm Sci, 2009,37(3):395-404.
[9] Joshi S A, Chavhan S S, Sawant K K. Rivastigmine-loaded PLGA and PBCA nanoparticles:Preparation, optimization, characterization, in vitro and pharmacodynamic studies[J]. Eur J Pharm Biopharm, 2010,76(2):189-199.
[10] Nippe S, General S. Combination of injectable ethinyl estradiol and drospirenone drug-delivery systems and characterization of their in vitro release[J]. Eur J Pharm Sci, 2012,47(4):790-800.
[11] Huang C Y, Lee Y D. Core-shell type of nanoparticles composed of poly copolymers for drug delivery application:Synthesis, characterization and in vitro degradation[J]. Int J Pharm, 2006,325(1):132-139.
[12] Dunne M, Corrigan O I, Ramtoola Z. Influence of particle size and dissolution conditions on the degradation properties of polylactide-co-glycolide particles[J]. Biomaterials, 2000,21(16):1659-1668.
[13] 肖丽君,赵恩宏,赵爽,等.17-AAG对MCF-7细胞增殖的抑制作用及对STAT3和VEGF表达的影响[J].中国医科大学学报,2013,42(1):65-68.

Studies on anticancer activity of 17-AAG poly-butylcyanoacrylate nanoparticles

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