Novel siRNA Delivery System Using a Ternary Polymer Complex with Strong Silencing Effect and No Cytotoxicity
スポンサーリンク
概要
- 論文の詳細を見る
We developed a novel small interfering RNA (siRNA) delivery system using a ternary complex with polyethyleneimine (PEI) and γ-polyglutamic acid (γ-PGA), which showed silencing effect and no cytotoxicity. The binary complexes of siRNA with PEI were approximately 73–102 nm in particle size and 45–52 mV in ζ-potential. The silencing effect of siRNA/PEI complexes increased with an increase of PEI, and siRNA/PEI complexes with a charge ratio greater than 16 showed significant luciferase knockdown in a mouse colon carcinoma cell line regularly expressing luciferase (Colon26/Luc cells). However, strong cytotoxicity and blood agglutination were observed in the siRNA/Lipofectamine complex and siRNA/PEI16 complex. Recharging cationic complexes with an anionic compound was reported to be a promising method for overcoming these toxicities. We therefore prepared ternary complexes of siRNA with PEI (charge ratio 16) by the addition of γ-PGA to reduce cytotoxicity and deliver siRNA. As expected, the cytotoxicity of the ternary complexes decreased with an increase of γ-PGA content, which decreased the ζ-potential of the complexes. A strong silencing effect comparable to siRNA/Lipofectamine complex was discovered in ternary complexes including γ-PGA with an anionic surface charge. The high incorporation of ternary complexes into Colon26/Luc cells was confirmed with fluorescence microcopy. Having achieved knockdown of an exogenously transfected gene, the ability of the complex to mediate knockdown of an endogenous housekeeping gene, glyceraldehyde 3-phosphate dehydrogenase (GAPDH), was assessed in B16-F10 cells. The ternary complex (siRNA/PEI16/γ-PGA12 complex) exhibited a significant GAPDH knockdown effect. Thus, we developed a useful siRNA delivery system.
- 公益社団法人 日本薬学会の論文
著者
-
Nakagawa Hiroo
Department Of Hospital Pharmacy Nagasaki University Hospital Of Medicine And Dentistry
-
KODAMA Yukinobu
Department of Clinical Pharmacy, Graduate School of Biomedical Sciences, Nagasaki University
-
Sasaki Hitoshi
Department Of Basic Pharmaceutics Faculty Of Pharmaceutical Sciences Kyoto University
-
Kitahara Takashi
Department Of Breast Oncology Cancer Institute Hospital Of Japanese Foundation For Cancer Research
-
Kitahara Takashi
Department of Hospital Pharmacy, Nagasaki University Hospital
-
Nakamura Tadahiro
Department of Hospital Pharmacy, Nagasaki University Hospital
-
Kurosaki Tomoaki
Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University
-
Higuchi Norihide
Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University
-
Muro Takahiro
Department of Hospital Pharmacy, Nagasaki University Hospital
-
Shiokawa Yumi
Department of Hospital Pharmacy, Nagasaki University Hospital
-
Aki Keisei
Department of Hospital Pharmacy, Nagasaki University Hospital
関連論文
- Change in Pharmacokinetics of Model Compounds with Different Elimination Processes in Rats during Hypothermia
- Highly stomach-selective gene transfer following gastric serosal surface instillation of naked plasmid DNA in rats.
- Ocular Pharmacokinetic/Pharmacodynamic Modeling for Multiple Anti-glaucoma Drugs
- Influence of murine hepatitis induced by D-(+)-galactosamine hydrochloride and lipopolysaccharide on gene expression of polyethylenimine/plasmid DNA polyplex
- Absorption and Distribution Characteristics of 5-Fluorouracil (5-FU) after an Application to the Liver Surface in Rats in Order to Reduce Systemic Side Effects
- Ocular Pharmacokinetic/Pharmacodynamic Modeling for Timolol in Rabbits Using a Telemetry System
- Electrophysiological Characterization of Tight Junctional Pathway of Rabbit Cornea Treated with Ophthalmic Ingredients
- Spleen-Selective Gene Transfer Following the Administration of Naked Plasmid DNA onto the Spleen Surface in Mice
- Unilateral Lung-Selective Gene Transfer Following the Administration of Naked Plasmid DNA onto the Pulmonary Pleural Surface in Mice
- Transport of Timolol and Tilisolol in Rabbit Corneal Epithelium
- Stomach-Selective Gene Transfer Following the Administration of Naked Plasmid DNA onto the Gastric Serosal Surface in Mice
- Partial Hepatectomy Enhances Polyethylenimine-Mediated Plasmid DNA Delivery
- PEGylated Liposomes Loading Palmitoyl Prednisolone for Prolonged Blood Concentration of Prednisolone
- Effect of Solution Composition of Plasmid DNA on Gene Transfection Following Liver Surface Administration in Mice
- Stomach- and Site-Selective Delivery of 5-Fluorouracil Following Its Application on the Gastric Serosal Surface in Rats
- Unilateral Kidney-Selective Gene Transfer Following the Administration of Naked Plasmid DNA to the Kidney Surface in Mice
- Liver Site-Specific Gene Transfer Following the Administration of Naked Plasmid DNA to the Liver Surface in Mice
- Antimicrobial Activity of Saturated Fatty Acids and Fatty Amines against Methicillin-Resistant Staphylococcus aureus
- Pharmacokinetics of Phenol Red in Rat Models of Liver Damage Prepared by Liver Targeting of Carbon Tetrachloride
- Biliary Excretion of Mitomycin C Dextran Conjugates in Relation of Physicochemical Characteristics of Carrier Dextran
- Transport of Acebutolol through Rabbit Corneal Epithelium
- Sensitive and Real-Time Method for Evaluating Corneal Barrier Considering Tear Flow
- In Vivo Ocular Pharmacokinetic Model for Designing Dosage Schedules and Formulations of Ophthalmic Drugs in Human
- Further Studies on the Kidney- and Site-Selective Delivery of 5-Fluorouracil Following Kidney Surface Application in Rats
- Effect of the Absorption Enhancer Saponin on the Intrarenal Distribution of 5-Fluorouracil Following Its Kidney Surface Application in Rats
- Kidney- and Site-Selective Delivery of 5-Fluorouracil Utilizing the Absorption on the Kidney Surface in Rats
- Change in Erythrocyte Shape Induced by Cyclosporine Administration
- Cellular Interaction and in Vitro Antitumor Activity of Lipophilic Mitomycin C Prodrugs(Pharmaceutical)
- Differences in Effects of Oncogenes on Sensitivity to Anticancer Drugs
- A Novel Method for Preparation of Animal Models of Liver Damage: Liver Targeting of Carbon Tetrachloride in Rats
- Biodistribution and Pharmacokinetics of O-Palmitoyl Tilisolol, a Lipophilic Prodrug of Tilisolol, after Intravenous Administration in Rats
- Continuous Microinstillation of Phenol Red on Liver Surface for Liver Site-Selective Delivery
- Modification of Ocular Permeability of Peptide Drugs by Absorption Promoters
- Pharmacokinetic Prediction of the Ocular Absorption of an Instilled Drug with Ophthalmic Viscous Vehicle
- Characterization of Ocular Pharmacokinetics of Tilisolol after Instillation into Anesthetized Rabbits
- Topical Delivery System of Ophthalimic Drugs by Periocular Injection with Viscous Solution
- Drug Absorption Behavior after Periocular Injections
- Induction of Micronuclei in CHO Cells by Bleomycin but not by X-irradiation is Decreased by Treatment with HMG-CoA Reductase Inhibitors
- Evaluation of Newly Developed Oxygen Meters with Multi-Channels and Disposable Oxygen Electrode Sensors for Antimicrobial Susceptibility Testing
- EFFECT OF SYNTHETIC SURFACTANTS ON DRUG ABSORPTION IN THE PRESENCE OF A PHYSIOLOGIC SURFACTANT, SODIUM TAUROCHOLATE, IN RATS
- AN ASSESSMENT OF GASTRIC ULCERS IN VIVO : ENHANCEMENT OF URINARY RECOVERY AFTER ORAL ADMINISTRATION OF PHENOLSULFONPHTHALEIN IN RATS
- DRUG ABSORPTION FROM THE GASTROINTESTINAL TRACT AND IMMUNITY : EFFECT OF ANAPHYLAXIS ON THE ABSORPTION OF SALICYLIC ACID FROM THE RAT SMALL INTESTINE
- ANTIGEN-INDUCED DECREASE OF SALICYLIC ACID ABSORPTION FROM THE SMALL INTESTINE IN ACTIVELY IMMUNIZED RATS
- Scintigraphic detection of recurrence of medullary thyroid cancer
- Influence of liver disease on phenolsulfonphthalein absorption from liver surface to examine possibility of direct liver surface application for drug targeting,
- Local Distribution into Brain Tumor and Pharmacokinetics of 4-Pyridoxate Diammine Hydroxy Platinum, a Novel Cisplatin Derivative, after Intracarotid Administration in Rats with 9L Malignant Glioma : Simultaneous Brain Microdialysis Study
- In Vitro Characteristics and in Vivo Plasma Disposition of Cisplatin Conjugated with Oxidized and Dicarboxymethylated Dextrans
- In Vivo Microdialysis to Determine the Relative Pharmacokinetics of Drugs
- Tissue Distribution of ^In-Labeled Uricase Conjugated with Charged Dextrans and Polyethylene Glycol
- CONTROL OF IN VIVO FATE OF PROTEIN DRUGS USING CHEMICAL MODIFICATION WITH SUGARS
- Design and Evaluation of Monoclonal Antibody-Antitumor Agent Conjugate
- Cellular Interaction and in Vitro Antitumor Effect of Various Mitomycin C Prodrugs in Mitomycin C-Resistant L1210 Leukemia Cell Lines(Pharmaceutical)
- CELLULAR INTERACTION AND ANTITUMOR ACTIVITY OF MITOMYCIN C PRODRUGS
- URINARY EXCRETION CHARACTERISTICS OF A POLYMERIC PRODRUG OF MITOMYCIN C, MITOMYCIN C-DEXTRAN CONJUGATE
- ENHANCED LYMPHATIC DELIVERY OF MIYOMYCIN C BY POLYMERIC MODIFICATION
- Mechanism of the Cardioprotective Effects of Docetaxel Pre-administration Against Adriamycin-Induced Cardiotoxicity
- ANTITUMOR ACTIVITY OF LIPOPHILIC PRODRUGS OF MITOMYCIN C ENTRAPPED IN LIPOSOME OR O/W EMULSION
- DEVELOPMENT OF LIPOPHILIC MITOMYCIN C PRODRUGS AND THEIR APPLICATION TO LIPID DISPERSION SYSTEMS
- Optimal Usage of Meropenem Based on Recommended Regimen Derived from Monte Carlo Simulation
- Hemispheric differences in color detection : a comparison of visual reaction times in human subjects
- ACUTE AND SUBACUTE TOXICITY STUDIES ON COLLAGEN WOUND DRESSING (CAS) IN MICE AND RATS
- Liver- and Lobe-Specific Gene Transfer Following the Continuous Microinstillation of Plasmid DNA onto the Liver Surface in Mice: Effect of Instillation Speed
- Fluorescence Investigation of the Retinal Delivery of Hydrophilic Compounds via Liposomal Eyedrops
- Metamorphosis Analysis of Consciousness Structure for Environment Problems
- Postmortem changes in tissue concentrations of triazolam and diazepam in rats
- Mechanism of the Cardioprotective Effects of Docetaxel Pre-administration Against Adriamycin-Induced Cardiotoxicity
- Chronopharmacology of Mizoribine in Collagen-Induced Arthritis Rats
- Chronopharmacology of Mizoribine in Collagen-Induced Arthritis Rats
- Newly Diagnosis of Malignant Glioma by the Expression of Metallothionein Isoforms
- Ocular Gene Delivery Systems Using Ternary Complexes of Plasmid DNA, Polyethylenimine, and Anionic Polymers
- Safe and Effective Delivery of Small Interfering RNA with Polymer- and Liposomes-Based Complexes
- Secure Splenic Delivery of Plasmid DNA and Its Application to DNA Vaccine
- Ternary Complex of Plasmid DNA with Protamine and γ-Polyglutamic Acid for Biocompatible Gene Delivery System
- Novel siRNA Delivery System Using a Ternary Polymer Complex with Strong Silencing Effect and No Cytotoxicity