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Cholesterol gene delivery systems

CDs also benefited cholesterol-containing gene delivery systems. These systems consisted of a DNA-lipid complex with cholesterol, which was assumed to improve cellular uptake of the complex. However, incomplete solubilization of cholesterol created the problem of aggregation. Thus methyl-p-CD-solubilized cholesterol was used instead of cholesterol to stabilize the formulation, which not only improved the permeability of the cell membrane but also the endosomal and nuclear membrane. Likewise, CD-cholesterol-schizophyllan complexes were also designed for oligonucleotide delivety. ° ... [Pg.234]

Cationic liposomes composed of 3(3- [ N- (N N-dimethylaminoethane (carbamoyl] cholesterol (DC-Chol) and dioleoylphosphatidylethanolamine (DOPE) (DC-Chol/DOPE liposome, molar ratio, 1 1 or 3 2) prepared by the dry-film method have been often used as non-vtral gene delivery vectors. We have shown that a more efficient transfection in medium with serum was achieved using DC-Chol/DOPE liposomes (molar ratio, 1 2) than those (3 2), and preparation method by a modified ethanol injection than the dry-film. The most efficient DC-Chol/DOPE liposome for gene transfer was molar ratio (1 2) and prepared by a modified ethanol injection method. The enhanced transfection is related to an increase in the release of DNA in the cytoplasm by the large lipoplex during incubation in opti-MEM 1 reduced-serum medium (optiMEM), not to an increased cellular association with the lipoplex. Cationic liposomes rich in DOPE prepared by a modified ethanol injection method will help to improve the efficacy of liposome vector systems for gene delivery. [Pg.393]

The therapeutic efficacy of either systemic or local pulmonary delivery of the IFN-y gene was evaluated in a murine allergen-induced airway hyperresponsiveness (AHR) model (Dow et al. 1999) and it was found that a high efficiency of gene transfer could be achieved. Intratracheal administered cationic liposomes were prepared from a mixture of l,2-diacylglycero-3-ethylphosphocholine (EDMPC) and cholesterol. Intravenous injections were prepared from l,2-dioleyl-3-trimethylammo-ninm propane (DOTAP) and cholesterol and compared with pulmonary administered... [Pg.266]

A number of factors for DOTAP-cholesterol/DNA complex preparation including the DNA/liposome ratio, mild sonication, heating, and extrusion were found to be crucial for improved systemic delivery maximal gene expression was obtained when a homogeneous population of DNA/liposome complexes (200-450 nm) was used. Cryoelectron microscopy showed that the DNA was condensed on the interior of liposomes between two lipid bilayers in these formulations, a factor that was thought to be responsible for the high transfection efficiency in vivo and for the broad tissue distribution (150). [Pg.352]

Liposomes applied on the skin were also investigated for their delivery proprieties to the pilosebaceous units [15,23 28]. The in vitro skin penetration behavior of carboxyfluorescein incorporated in multilamellar liposomes (phosphatidylcholine cholesterol phosphatidylser-ine) and in another four nonliposomal systems (HEPES pH 7.4 buffer 5% propylene glycol 10% ethanol and 0.05% sodium lauryl sulfate) was studied by Lieb et al. [25]. Using two fluorescent techniques the authors found a higher accumulation of the probe within skin follicles when delivered from liposomes [25], Further, in an interesting setup of in vitro and in vivo experiments in mice, Hoffman s group observed liposomal delivery of the active Lac-Z gene and its expression mostly in the hair follicles [26,28]. [Pg.257]

The rate of liposome accumulation in alveolar type-II cells is dependent on lipid composition. It is therefore possible to select liposome compositions displaying minimal interaction with these cells and thereby function as controlled-release systems for entrapped solutes. For example, liposomes composed of dipalmitoylphosphatidylcholine and cholesterol and containing entrapped sodium cromoglycate will provide sustained delivery of the drag for over 24 hours. Conversely other liposome compositions could be utilized for enhanced epithelial interaction and transport of the drug (e g. cationic lipids for the cellular delivery of the CFTR gene). [Pg.272]


See other pages where Cholesterol gene delivery systems is mentioned: [Pg.1105]    [Pg.1161]    [Pg.3506]    [Pg.250]    [Pg.368]    [Pg.393]    [Pg.283]    [Pg.1530]    [Pg.217]    [Pg.67]    [Pg.190]    [Pg.192]    [Pg.37]    [Pg.165]    [Pg.30]    [Pg.401]    [Pg.32]    [Pg.667]    [Pg.483]    [Pg.2052]    [Pg.16]    [Pg.439]   
See also in sourсe #XX -- [ Pg.234 ]




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