Controlled delivery of drugs through smart pH-sensitivenanohydrogels for anti-cancer therapies: synthesis, drug release and cellular studies

被引:16
作者
Alvarez-Bautista, A. [1 ,2 ,3 ]
Duarte, C. M. M. [2 ,3 ]
Mendizabal, E. [4 ]
Katime, I. [1 ]
机构
[1] Univ Basque Country, Dept Phys Chem, New Mat & Supramol Spect Grp, UPV EHU, Bilbao, Spain
[2] Univ Nova Lisboa, Inst Tecnol Quim & Biol, Oeiras, Portugal
[3] Inst Biol Expt & Tecnol, Nutraceut & Controlled Delivery Lab, Oeiras, Portugal
[4] Univ Guadalajara, CUCEI, Guadalajara 44430, Jalisco, Mexico
关键词
Delivery; cancer cells; nanohydrogels; nanoparticles; smart nanocarriers; POLY(DIVINYLBENZENE) MICROSPHERES; MICROGELS; POLYMERIZATION; ACID;
D O I
10.1080/15685551.2016.1152542
中图分类号
O63 [高分子化学(高聚物)];
学科分类号
070305 ; 080501 ; 081704 ;
摘要
Nanohydrogels were synthesized by microemulsion polymerization. These nanohydrogels were pre-designed to be pH and temperature stimuli-response materials, using N-isopropylacrilamide as a base monomer and 1-vinyl imidazole as ionizable comonomer. The pH sensitivity was confirmed by measuring the increase or decrease in volume in the nanoparticles by changing the pH of the medium. Nanoparticles were properly characterized by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), nuclear magnetic resonance (NMR) and transmission electron microscopy (TEM). Glass-transition temperature increased with vinyl imidazole content, and nanoparticles with average diameter of 68nm were obtained. Particle size decreases with the increase in pH. After characterization, nanohydrogels were functionalized with folic acid to take advantage that the folate receptor is overexpressed in different types of cancer cells. The nanoparticles were loaded with the drugs: metformin, terfenadine, and 5-fluorouracil. The amount of drug loaded and released by nanoparticles was measured by UV-vis spectroscopy. Then, cellular viability and internalization studies were performed obtaining promising results.
引用
收藏
页码:319 / 329
页数:11
相关论文
共 25 条
[1]   Synthesis and characterization of novel pH-responsive microgels based on tertiary amine methacrylates [J].
Amalvy, JI ;
Wanless, EJ ;
Li, Y ;
Michailidou, V ;
Armes, SP ;
Duccini, Y .
LANGMUIR, 2004, 20 (21) :8992-8999
[2]   Folate-targeted PEG as a potential carrier for carboplatin analogs. Synthesis and in vitro studies [J].
Aronov, O ;
Horowitz, AT ;
Gabizon, A ;
Gibson, D .
BIOCONJUGATE CHEMISTRY, 2003, 14 (03) :563-574
[3]   Design and release characteristics of sustained release tablet containing metformin HCl [J].
Basak, Subal Chandra ;
Kumar, Kesevan Senthil ;
Ramalingam, Murugesan .
REVISTA BRASILEIRA DE CIENCIAS FARMACEUTICAS, 2008, 44 (03) :477-483
[4]  
Blanco MD, 2008, METHOD FIND EXP CLIN, V30, P121
[5]  
Boggs LJ, 1996, J COATING TECHNOL, V68, P63
[6]  
Choi HS, 1998, J APPL POLYM SCI, V69, P799, DOI 10.1002/(SICI)1097-4628(19980725)69:4<799::AID-APP19>3.0.CO
[7]  
2-K
[8]   Growth mechanism of poly(divinylbenzene) microspheres in precipitation polymerization [J].
Downey, JS ;
Frank, RS ;
Li, WH ;
Stöver, HDH .
MACROMOLECULES, 1999, 32 (09) :2838-2844
[9]   Influence of reaction conditions on the synthesis of self-cross-linked N-isopropylacrylamide microgels [J].
Gao, J ;
Frisken, BJ .
LANGMUIR, 2003, 19 (13) :5217-5222
[10]   Smart copolymeric nanohydrogels: Synthesis, characterization and properties [J].
Guerrero-Ramirez, L. G. ;
Nuno-Donlucas, S. M. ;
Cesteros, L. C. ;
Katime, I. .
MATERIALS CHEMISTRY AND PHYSICS, 2008, 112 (03) :1088-1092