title: Fully glutathione degradable waterborne polyurethane nanocarriers: Preparation, redox-sensitivity, and triggered intracellular drug release.
abstract: Polyurethanes are important class of biomaterials that are extensively used in medical devices. In spite of their easy synthesis, polyurethanes that are fully degradable in response to the intracellular reducing environment are less explored for controlled drug delivery. Herein, a novel glutathione degradable waterborne polyurethane (WPU) nanocarrier for redox triggered intracellular delivery of a model lipophilic anticancer drug, doxorubicin (DOX) is reported. The WPU was prepared from polyaddition reaction of isophorone diisocyanate (IPDI) and a novel linear polyester polyol involving disulfide linkage, disulfide labeled chain extender, dimethylolpropionic acid (DMPA) using dibutyltin dilaurate (DBTDL) as a catalyst. The resulting polyurethane self-assembles into nanocarrier in water. The dynamic light scattering (DLS) measurements and scanning electron microscope (SEM) revealed fast swelling and disruption of nanocarriers under an intracellular reduction-mimicking environment. The in vitro release studies showed that DOX was released in a controlled and redox-dependent manner. MTT assays showed that DOX-loaded WPU had a high in vitro antitumor activity in both HDF noncancer cells and MCF- 7 cancer cells. In addition, it is found that the blank WPU nanocarriers are nontoxic to HDF and MCF-7 cells even at a high concentration of 2mg/mL. Hence, nanocarriers based on disulfide labeled WPU have appeared as a new class of biocompatible and redox-degradable nanovehicle for efficient intracellular drug delivery.
authors: Department of polymer, Faculty of Chemistry, Shahid Beheshti University, G.C. 1983963411, Tehran, Iran.
authors: Ismail
authors: I
authors: Omrani
authors: Department of polymer, Faculty of Chemistry, Shahid Beheshti University, G.C. 1983963411, Tehran, Iran.
authors: Niloofar
authors: N
authors: Babanejad
authors: Department of polymer, Faculty of Chemistry, Shahid Beheshti University, G.C. 1983963411, Tehran, Iran.
authors: Hasan Kashef
authors: HK
authors: Shendi
authors: Department of polymer, Faculty of Chemistry, Shahid Beheshti University, G.C. 1983963411, Tehran, Iran. Electronic address: m-nabid@sbu.ac.ir.
authors: Mohammad Reza
authors: MR
authors: Nabid
mesh_terms: D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002850:Chromatography, Gel; D004220:Disulfides / Q000737:chemistry; D004317:Doxorubicin / Q000494:pharmacology*; D004337:Drug Carriers / Q000737:chemistry*; D065546:Drug Liberation; D000067493:Dynamic Light Scattering; D004705:Endocytosis / Q000187:drug effects; D005978:Glutathione / Q000737:chemistry*; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism*; D061986:MCF-7 Cells; D008823:Micelles; D008856:Microscopy, Fluorescence; D053758:Nanoparticles / Q000737:chemistry; D010084:Oxidation-Reduction; D010316:Particle Size; D011091:Polyesters / Q000737:chemistry; D011140:Polyurethanes / Q000138:chemical synthesis / Q000737:chemistry*; D066244:Proton Magnetic Resonance Spectroscopy; D017550:Spectroscopy, Fourier Transform Infrared; D014867:Water / Q000737:chemistry*
chemical_list: D004220:Disulfides; D004337:Drug Carriers; D008823:Micelles; D011091:Polyesters; D011140:Polyurethanes; D014867:Water; D004317:Doxorubicin; D005978:Glutathione
keywords: Intracellular drug release; Redox-responsive; Waterborne PU