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| A NOVEL SERIES OF AMPHIPHILIC IMIDAZOLINIUM COMPOUNDS FOR IN-VITRO AND IN-VIVO GENE DELIVERY |
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| Author(s): SOLODIN I, BROWN CS, BRUNO MS, CHOW CY, JANG EH, DEBS RJ, HEATH TD |
| Source: BIOCHEMISTRY Volume: 34 Issue: 41 Pages: 13537-13544 Published: OCT 17 1995 |
| Times Cited: 158 References: 37 |
| Abstract: We have developed three catioinic amphiphiles based on the structure 1-[2-(acyloxy)ethyl]-2-alkyl(alkenyl)-3-(2-hydroxyethyl)imidazolinium chloride. Although these three compounds differ only in the structure of the hydrophobic acyl chains, they differ greatly in their ability to mediate in vivo and in vitro gene delivery. Moreover, in vitro efficiency is not predictive of in vivo efficiency. The myristoyl form is the most effective compound in vitro, and the oleoyl form is the most effective compound in vivo. The compounds readily form suspensions in aqueous media, both in the pure form and as mixtures with either cholesterol or dioleoylphosphatidylethanolamine. These suspensions can be sonicated to produce smaller particles. Particle size, electron microscopy, and the ability to capture glucose suggest that these lipids form liposomes on suspension in aqueous media. When mixed with plasmid DNA, the lipid particles appear to fuse and form larger particles. Fusion is maximal at the critical DNA:lipid ratio where extensive aggregation and precipitation are observed. Therefore, these compounds behave similarly to other cationic liposome-forming lipids upon interaction with DNA. |
| Document Type: Article |
| Language: English |
Addresses:
1. UNIV WISCONSIN, SCH PHARM, MADISON, WI 53706 USA
2. UNIV CALIF SAN FRANCISCO, MED CTR, CANC RES INST, SAN FRANCISCO, CA 94143 USA |
| Publisher: AMER CHEMICAL SOC, PO BOX 57136, WASHINGTON, DC 20037-0136 |
| Subject Category: Biochemistry & Molecular Biology |
| IDS Number: TB584 |
| ISSN: 0006-2960 |
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