title: Oral delivery of nanoparticles containing anticancer SN38 and hSET1 antisense for dual therapy of colon cancer.
abstract: An oral delivery system intended for treatment of colon cancer in HT29 cancerous cells was investigated by encapsulating hSET1 antisense and SN38 anticancer in nanoparticles based on cysteine trimethyl chitosan (cysTMC) and carboxymethyl dextran (CMD). Studies have shown hSET1 as the main type of histone methyltransferase (HMT) complex, is significantly overexpressed in malignant cells. In this study, hSET1 antisense was employed to inhibit gene expression. Additionally, SN38 was incorporated into nanoparticles to enhance the efficiency of the system by inhibition of topoisomerase 1. CysTMC was synthetized and characterized by (1)H NMR and FTIR. Nanoparticles were prepared through complexation of CMD and cysTMC. Particle size and surface charge was 100-150 nm and 17-21 mV respectively with drug content of around 2.6%. Gel electrophoresis assay proved the stability of antisense in simulated gastric and intestinal fluids. Nanoparticles showed high mucoadhesion and glutathione responsive release. Cellular uptake was observed by confocal microscopy and quantified by flow cytometry. Cytotoxicity of NPs was assessed using MTT assay. Results showed hSET1/SN38 nanoparticles had significantly higher cytotoxicity against HT29 cells compared with nanoparticles containing SN38, free SN38 or naked hSET1. Therefore, present system could be considered an effective combination therapy of highly hydrophobic SN38 and hSET1.
authors: Department of Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 1714614411, Iran.
authors: M
authors: M
authors: Dinarvand
authors: Department of Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 1714614411, Iran.
authors: M
authors: M
authors: Kiani
authors: Department of Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 1714614411, Iran.
authors: F
authors: F
authors: Mirzazadeh
authors: Department of Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 1714614411, Iran.
authors: A
authors: A
authors: Esmaeili
authors: Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors: Z
authors: Z
authors: Mirzaie
authors: Department of Hematology, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
authors: M
authors: M
authors: Soleimani
authors: Department of Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 1714614411, Iran; Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors: R
authors: R
authors: Dinarvand
authors: Department of Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 1714614411, Iran; Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: atyabifa@tums.ac.ir.
authors: F
authors: F
authors: Atyabi
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D045744:Cell Line, Tumor; D048271:Chitosan / Q000737:chemistry; D003110:Colonic Neoplasms / Q000473:pathology / Q000628:therapy; D004195:Disease Models, Animal; D004337:Drug Carriers / Q000737:chemistry; D065546:Drug Liberation; D004355:Drug Stability; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics*; D006801:Humans; D000077146:Irinotecan; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage*; D017550:Spectroscopy, Fourier Transform Infrared; D023041:Xenograft Model Antitumor Assays
chemical_list: D004337:Drug Carriers; D016376:Oligonucleotides, Antisense; D000077146:Irinotecan; D048271:Chitosan; D011495:Histone-Lysine N-Methyltransferase; C526068:Setd1A protein, human; D002166:Camptothecin
keywords: Chitosan; Nanoparticles; Oral drug delivery