title: Temperature- and pH-responsive nanoparticles of biocompatible polyurethanes for doxorubicin delivery.
abstract: A series of temperature- and pH-responsive polyurethanes based on hexamethylene diisocyanate (HDI) and 4,4'-diphenylmethane diisocyanate (MDI) were synthesized by a coupling reaction with bis-1,4-(hydroxyethyl) piperazine (HEP), N-methyldiethanolamine (MDEA) and N-butyldiethanolamine (BDEA), respectively. The chemical structure, molecular weight, thermal property and crystallization properties were characterized by Fourier transform infrared (FT-IR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, gel permeation chromatography (GPC), differential scanning calorimetry (DSC) and X-ray diffraction (XRD) spectroscopy. The resulting polyurethanes were then used to prepare nanoparticles either by direct dispersion method or dialysis method. Their pH and temperature responsibilities were evaluated by optical transmittance and size measurement in aqueous media. Interestingly, HDI-based and MDI-based polyurethanes exhibited different pH and temperature responsive properties. Nanoparticles based on HDI-HEP and HDI-MDEA were temperature-responsive, while MDI-based biomaterials were not. All of them showed pH-sensitive behavior. The possible responsive mechanism was investigated by (1)H NMR spectroscopy. The cytotoxicity of the polyurethanes was evaluated using methylthiazoletetrazolium (MTT) assay in vitro. It was shown that the HDI-based polyurethanes were non-toxic, and could be applied to doxorubicin (DOX) encapsulation. The experimental results indicated that DOX could be efficiently encapsulated into polyurethane nanoparticles and uptaken by Huh-7 cells. The loaded DOX molecules could be released from the drug-loaded polyurethane nanoparticles upon pH and temperature changes, responsively.
authors.affiliation: School of Chemistry and Chemical Engineering, Tianjin University of Technology, Tianjin 300384, China.
authors.forename: Anning
authors.initials: A
authors.lastname: Wang
authors.forename: Hui
authors.initials: H
authors.lastname: Gao
authors.forename: Yanfang
authors.initials: Y
authors.lastname: Sun
authors.forename: Yu-long
authors.initials: YL
authors.lastname: Sun
authors.forename: Ying-Wei
authors.initials: YW
authors.lastname: Yang
authors.forename: Guolin
authors.initials: G
authors.lastname: Wu
authors.forename: Yinong
authors.initials: Y
authors.lastname: Wang
authors.forename: Yunge
authors.initials: Y
authors.lastname: Fan
authors.forename: Jianbiao
authors.initials: J
authors.lastname: Ma
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000473:pathology; D045744:Cell Line, Tumor; D003460:Crystallization; D003485:Cyanates / Q000737:chemistry; D004317:Doxorubicin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D017953:Isocyanates / Q000737:chemistry; D008113:Liver Neoplasms / Q000188:drug therapy / Q000473:pathology; D008970:Molecular Weight; D053758:Nanoparticles; D010316:Particle Size; D011140:Polyurethanes / Q000737:chemistry*; D013696:Temperature; D001559:Benzhydryl Compounds
chemical_list: D000903:Antibiotics, Antineoplastic; D003485:Cyanates; D004317:Doxorubicin; D004337:Drug Carriers; D017953:Isocyanates; D011140:Polyurethanes; C015262:1,6-hexamethylene diisocyanate; C005969:4,4'-diphenylmethane diisocyanate; D001559:Benzhydryl Compounds