In vivo anti-tumor efficacy of docetaxel-loaded thermally responsive nanohydrogel.
Thermally responsive poly(N-isopropylacrylamide-co-acrylamide) (P(NIPA-co-AAm)) nanohydrogel (NHG) with a diameter of about 50 nm and a lower critical solution temperature (LCST) of about 40 degrees C was synthesized by a previously reported precipitation polymerization method. The physical properties including LCST, diameter and morphology were characterized. Four hydrophobic model drugs (5-fluorouracil (5-FU), fluorescein, docetaxel (DTX) and near-infrared dye-12 (NIRD-12)) with different hydrophilicities were respectively entrapped into the nanoparticles and their in vitro release kinetics from NHG was investigated. DTX was ultimately chosen as the goal anti-tumor drug and optimally entrapped into NHG with a drug loading content (DLC) of 7.38% and encapsulation efficiency (EE) of 73.8%. An in vitro drug release test indicated that DTX-loaded NHG had zero-order release kinetics at 43 degrees C. The respective anti-tumor efficacy of DTX-loaded NHG with or without hyperthermia on tumor tissue was evaluated in Kunming mice-bearing S180 sarcoma. The inhibition rates of DTX-loaded NHG with or without hyperthermia were 78.15% and 48.78%, respectively. DTX-loaded NHG also showed much lower toxicity during the therapeutic procedure. Results indicated that this kind of thermally responsive, drug-loaded NHG could be used as a promising strategy for tumor therapy with the help of local hyperthermia treatment.
Zhang
Jian
J
Department of Biomedical Engineering, School of Life Science and Technology, China Pharmaceutical University, Tongjia Lane No. 24, Nanjing 210009, People's Republic of China.
Qian
Zhiyu
Z
Gu
Yueqing
Y
D000180:Acrylic Resins / Q000737:chemistry; D000818:Animals; D000077143:Docetaxel; D016503:Drug Delivery Systems; D019793:Fluorescein / Q000378:metabolism; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry*; D007700:Kinetics; D051379:Mice; D049329:Nanostructures / Q000737:chemistry*; D010316:Particle Size; D043823:Taxoids / Q000008:administration & dosage* / Q000494:pharmacology*; D013696:Temperature; D013997:Time Factors; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays
D000180:Acrylic Resins; D043823:Taxoids; C469412:poly(N-isopropylacrylamide-co-acrylamide); D000077143:Docetaxel; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D019793:Fluorescein