Back to Search
Start Over
Targeting hepatocytes with liposomal interferon-alpha: effect on metallothionein gene induction.
- Source :
-
Research communications in molecular pathology and pharmacology [Res Commun Mol Pathol Pharmacol] 2002; Vol. 112 (1-4), pp. 50-8. - Publication Year :
- 2002
-
Abstract
- Interferon-alpha (INF-alpha) is the only effective drug for the treatment of chronic hepatitis B. However it can produce severe side effects during treatment. Encapsulation of INF-alpha in liposomes may reduce the side effects and enhance its therapeutic activity. We evaluated the activity of free (nonencapsulated) and liposome-encapsulated INF-alpha on in vitro cultured Chang liver cells by measuring the metallothionein gene (MT-IIA). INF-alpha was encapsulated in different liposomal formulations, Dimyristoylphosphatidylcholine (DMPC), Dioleyl-phosphatidyl-ethanolamine/Dimyristoylphosphatidylcholine (DOPE/DMPC) and DOPE/Dimyristoylphosphatidylglycerol (DOPE/DMPG). Chang liver cells were incubated for 10 hours with 100 units/ml of free or one of the aforementioned liposomal INF-alpha formulations. We also evaluated the extended-time effects of DMPC liposomal formulations of INF-alpha and the non-encapsulated (free) INF-alpha on Chang liver cells after 12, 24 and 36 h of incubation. Total RNA was extracted and signals on Northern blots were densitometrically compared following hybridization with MT-IIA and beta actin probes. All INF-alpha formulations (free and liposomal) induced higher MT-IIA gene levels compared to non-treated control cells. Levels of MT-IIA mRNA expression were 80.9, 73.6, 43.9, and 35.3% over the control for the free, DOPE/DMPG, DMPC and DOPE/DMPC liposomal INF-alpha, respectively. The ratios of MT-IIA mRNA amounts expressed after the Chang liver cells were incubated with INF-alpha encapsulated in DMPC liposomes and the MT-IIA mRNA expressed after incubation with nonencapsulated INF-alpha are 0.7, 0.52 and 0.82 at 12, 24, and 36 hours, respectively. The results indicate that the MT-IIA mRNA level depends on the liposomal formulation of INF-alpha, and the sustained-time effect of the INF-alpha encapsulated in DMPC liposomes is parallel to that of nonencapsulated INF-alpha over a period of 36 hours.
- Subjects :
- Animals
Blotting, Northern
Cell Line
DNA Probes
Drug Compounding
Drug Delivery Systems
Gene Expression Regulation drug effects
Interferon-alpha administration & dosage
Liposomes
RNA, Messenger biosynthesis
RNA, Messenger isolation & purification
Tissue Distribution
Transcriptional Activation
Hepatocytes metabolism
Interferon-alpha pharmacology
Metallothionein biosynthesis
Metallothionein genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1078-0297
- Volume :
- 112
- Issue :
- 1-4
- Database :
- MEDLINE
- Journal :
- Research communications in molecular pathology and pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 15080496