Many drawbacks of viral gene delivery agents might be overcome by nonviral systems; studies in patients suggest these systems have potential as therapies and as vaccines.
A liposome system was developed which demonstrates suitability as an intravenous drug carrier for a lipophilic drug compound (RS-93522, a dihydropyridine CA2+ channel blocker). An aqueous ...phospholipid suspension was employed as a nontoxic solubilizing vehicle for this drug. The liposome formulation, composed of a 3% mixture of dioleoylphosphatidylcholine and dioleoylphosphatidylglycerol, produced a physically and chemically stable preparation which solubilized the lipophilic drug compound at a concentration 500 times above its intrinsic aqueous solubility. Characterizing the liposome-drug system by gel filtration chromatography showed that the drug comigrated with the lipid constituents of the liposome. Further in vitro studies established that the liposome-RS-93522 formulation allowed for rapid and complete transfer of the drug from the liposome to bind with albumin when added to human serum. In vivo studies with rats were performed in which the pharmacokinetics of the liposomal-RS-93522 system were compared to those of a cosolvent-solubilized RS-93522 solution. This study showed that the pharmacokinetic profiles of the two solutions were identical. All the evidence indicates that a liposome formulation of this type does not alter the distribution of the drug in serum and is, therefore, not likely to affect the intrinsic pharmacological or toxicological parameters of the drug relative to the conventional solvent/excipient-containing formulation. This liposome system demonstrates utility as a biocompatible, nontoxic drug delivery vehicle.
The chapter charts out the progress in gene-delivery research and development. This chapter begins with gene delivery early in vitro transfection studies and then discusses the molecular biology and ...biotechnology applications for DNA transfection. This is followed by the application of synthetic vectors for gene therapy. During the last few years, substantial progress in the application of synthetic gene-delivery systems has been witnessed. Lastly, the chapter presents an overview of developing more-efficient synthetic gene-delivery systems. The discussion concludes with the fact that the science of synthetic gene-delivery system discovery is still at an early stage. There are several ways in which the current-generation vectors can be improved. As these different approaches are explored and new developments are introduced, it can be anticipated that improved delivery systems will emerge. Delivery systems that confer higher levels of in vivo gene product expression should yield increasingly successful clinical outcomes.
The hexokinase: fumarase ratios of mitochondria isolated from ten tissues of the rat were determined, and compared with the tissue content of phosphoglucomutase and phosphorylase, taken as ...representatives of enzymes concerned with glycogen metabolism. A generally inverse relationship was found between the mitochondrial hexokinase: fumarase ratio and phosphoglucomutase levels. The cytochrome: fumarase ratios were relatively invariant in these same mitochondria. The results are interpreted as indicating a specialization of mitochondria, with increased amounts to hexokinase being associated with the mitochondria in tissues exhibiting less dependence on glycogen metabolism, as judged from phosphoglucomutase levels.
Making gene therapy work Friedmann, Theodore; Felgner, Philip L; Blaese, R Michael ...
Scientific American,
06/1997, Volume:
276, Issue:
6
Magazine Article
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