title: Combined delivery of the adiponectin gene and rosiglitazone using cationic lipid emulsions.
abstract: For the combined delivery of an insulin-sensitizing adipokine; i.e., the ADN gene, and the potent PPARγ agonist rosiglitazone, cationic lipid emulsions were formulated using the cationic lipid DOTAP, helper lipid DOPE, castor oil, Tween 20 and Tween 80. The effect of drug loading on the physicochemical characteristics of the cationic emulsion/DNA complexes was investigated. Complex formation between the cationic emulsion and negatively charged plasmid DNA was confirmed and protection from DNase was observed. The in vitro transfection efficiency and cytotoxicity were evaluated in HepG2 cells. The particle sizes of the cationic emulsion/DNA complex were in the range 230-540 nm and those of the rosiglitazone-loaded cationic emulsion/DNA complex were in the range 220-340 nm. Gel retardation of the complexes was observed when the complexation weight ratios of the cationic lipid to plasmid DNA exceeded 4:1 for both the drug-free and rosiglitazone-loaded complexes. Both complexes stabilized plasmid DNA against DNase. The ADN expression level increased dose-dependently when cells were transfected with the cationic emulsion/DNA complexes. The rosiglitazone-loaded cationic emulsion/DNA complexes showed higher cellular uptake in HepG2 cells depending on the rosiglitazone loading, but not depending on the type of plasmid DNA type such as pVAX/ADN, pCAG/ADN, or pVAX. The drug-loaded cationic emulsion/plasmid DNA complexes were less cytotoxic than free rosiglitazone. Therefore, a cationic emulsion could potentially serve as a co-delivery system for rosiglitazone and the adiponectin gene.
authors: Department of Physical Pharmacy, College of Pharmacy, Chungnam National University, Daejeon 305-764, Republic of Korea; Institute of Drug Research and Development, Chungnam National University, Daejeon 305-764, Republic of Korea.
authors: Enkhzaya
authors: E
authors: Davaa
authors: Department of Physical Pharmacy, College of Pharmacy, Chungnam National University, Daejeon 305-764, Republic of Korea.
authors: Bong-Seok
authors: BS
authors: Kang
authors: Department of Pharmacology, College of Pharmacy, Chungnam National University, Daejeon 305-764, Republic of Korea.
authors: Joo-Hui
authors: JH
authors: Han
authors: Department of Physical Pharmacy, College of Pharmacy, Chungnam National University, Daejeon 305-764, Republic of Korea.
authors: Sang-Eun
authors: SE
authors: Lee
authors: Department of Physical Pharmacy, College of Pharmacy, Chungnam National University, Daejeon 305-764, Republic of Korea.
authors: Choon Lian
authors: CL
authors: Ng
authors: Department of Pharmacology, College of Pharmacy, Chungnam National University, Daejeon 305-764, Republic of Korea; Institute of Drug Research and Development, Chungnam National University, Daejeon 305-764, Republic of Korea.
authors: Chang-Seon
authors: CS
authors: Myung
authors: Department of Physical Pharmacy, College of Pharmacy, Chungnam National University, Daejeon 305-764, Republic of Korea; Institute of Drug Research and Development, Chungnam National University, Daejeon 305-764, Republic of Korea. Electronic address: eicosa@cnu.ac.kr.
authors: Jeong-Sook
authors: JS
authors: Park
mesh_terms: D052242:Adiponectin / Q000235:genetics*; D002412:Cations / Q000737:chemistry; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000737:chemistry; D016503:Drug Delivery Systems; D004655:Emulsions / Q000737:chemistry; D056945:Hep G2 Cells; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D010316:Particle Size; D000077154:Rosiglitazone; D013499:Surface Properties; D045162:Thiazolidinediones / Q000737:chemistry / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D052242:Adiponectin; D002412:Cations; D004655:Emulsions; D008055:Lipids; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D004247:DNA
keywords: Adiponectin; Cationic emulsion; Gene delivery; Rosiglitazone; Type 2 diabetes