title: In vivo drug delivery of gemcitabine with PEGylated single-walled carbon nanotubes.
abstract: Gemcitabine (GEM) is an anticancer agent widely used in non-small cell lung and pancreatic cancers. The clinical use of GEM has been limited by its rapid metabolism and short plasma half-life. These restrictions lead to frequent administration of high drug doses which can cause severe side effects. Therefore, new delivery strategies are needed aiming toward improved therapeutic effects. Single-walled carbon nanotubes (SWCNTs) are emerging as promising carriers for drug delivery due to their unique properties including high drug loading capacities, notable cell membrane penetrability and prolonged circulation times. In this work, pristine SWCNTs were functionalized through carboxylation, acylation, amination, PEGylation and finally GEM conjugation. The prepared SWCNT-GEM and SWCNT-PEG-GEM conjugates were characterized by FTIR, NMR, DSC and TEM to confirm the successful functionalization. The amount of GEM bound to the conjugates was 43.14% (w/w) for the SWCNT-GEM and 37.32% for the SWCNT-PEG-GEM, indicating high loading capacity. MTT assay on the human lung carcinoma cell line (A549) and the human pancreatic carcinoma cell line (MIA PaCa-2) demonstrated that the SWCNT-GEM was more cytotoxic than SWCNT-PEG-GEM and GEM. The SWCNT-PEG-GEM conjugates afford higher efficacy in suppressing tumor growth than SWCNT-GEM and GEM in B6 nude mice. The results demonstrate that the new formulation of GEM is useful strategy for improving the antitumor efficacy of GEM.
authors.affiliation: Department of Medical Physics and Biomedical Engineering, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Ali
authors.initials: A
authors.lastname: Razzazan
authors.affiliation: Department of Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: atyabifa@tums.ac.ir.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Atyabi
authors.affiliation: Department of Biotechnology, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Bahram
authors.initials: B
authors.lastname: Kazemi
authors.affiliation: Department of Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Rassoul
authors.initials: R
authors.lastname: Dinarvand
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000737:chemistry* / Q000627:therapeutic use / Q000633:toxicity; D002152:Calorimetry, Differential Scanning; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000627:therapeutic use / Q000633:toxicity; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry*; D065546:Drug Liberation; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008819:Mice, Nude; D046529:Microscopy, Electron, Transmission; D037742:Nanotubes, Carbon / Q000737:chemistry*; D009369:Neoplasms / Q000188:drug therapy; D011092:Polyethylene Glycols / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared; D014183:Transplantation, Heterologous; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D004337:Drug Carriers; D037742:Nanotubes, Carbon; D003841:Deoxycytidine; D011092:Polyethylene Glycols; D000093542:Gemcitabine
keywords: A549; MIA PaCa-2; Single-walled carbon nanotubes; gemcitabine; intracellular drug delivery; polyethylene glycol