A Microsphere-Liposome (Microplex) Vector for Targeted Gene Therapy of Cancer. II. In Vivo Biodistribution Study in a Solid Tumor Model

Abstract

Cationic liposomes are commonly used for transfection of plasmids into mammalian cells, while microspheres have been traditionally used for selective delivery of anticancer agents into tumor vasculature. We have developed a novel vector, comprised of cationic liposomes electrostatically bound to ion-exchange microspheres (termed 'microplex') for targeted gene therapy of solid tumors. The delivery modes tested in a rat solid tumor model were free plasmids, plasmids bound to microspheres, to liposomes, or to the combination vector. The greatest amount of chloramphenicol acetyltransferase (CAT) reporter gene expression in tumors was achieved using the microplex vector; 3.4-fold compared with free, and 1.8-fold compared with both microspherical and liposomal deliveries (p < 0.01). Tumor-to-normal kidney tissue CAT expression ratios were as follows: free 1.9:1; microspherical 3.7:1; liposomal 1.4:1 and microplexical 2.7:1. Expression between the two types of tissues was significantly different (p < 0.01) for all delivery modes. Microspheres targeted the plasmids to the tumors, while the action of cationic liposomes on cellular membranes allowed more plasmids to breach the cell membrane. This study has proven that the novel microplex vector is capable of selective delivery of genes to tumors and has the potential to target genes in clinical trials.

A novel orthotopic murine model provides insights into cellular and molecular characteristics contributing to human osteosarcoma

“…Cells were transfected in Opti-MEM reduced serum medium with 300 ng of pAcGFP1-N3 (BD-Biosciences, Australia) plasmid and 2.5 or 5 lL of Lipofectamine reagent (Invitrogen, Australia) as per Dass et al [12] with modifications. Cells were cultivated in the presence of G418 (Sigma-Aldrich) at 400 lg/mL from day 3, sorted at day 14 and then again on day 28 post-transfection.…”

Apolipoprotein A-I, Phospholipid Vesicles, and Cyclodextrins as Potential Anti-Atherosclerotic Drugs: Delivery, Pharmacokinetics, and Efficacy

“…These vesicles are commonly sized using polycarbonate lters with pore sizes depending on the diameter required for the vesicles (Dass 1998;Dass et al 1999bDass et al , 1999c. Liposomes may be specialized by the addition of various ligands or chemicals on or into their bilayer coats their allowing them to function for a given task better (reviewed in Dass et al 1997b).…”

Characterization, biodistribution and targeting evaluation of breviscapine lipid emulsions following intravenous injection in mice

“…Lipid emulsions are one of the lipid-based drug delivery systems such as liposomes and solid lipid nanoparticles. The transformation of a free drug into lipid-based drug delivery systems is a strategy to control and modify its pharmacokinetics and tissue distribution (Baldeschweiler, 1990;Dass et al, 2000;Hong et al, 2001;Ji et al, 2006;Tang et al, 2010). In the present research, we studied pharmacokinetics, tissue distribution, and targeting property of breviscapine lipid emulsions.…”