• Journal of Pharmaceutical Investigation
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• v.38 no.1
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• pp.15-21
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• 2008

Liposomes as one of the efficient drug carriers have some shortcomings such as their short circulation time, fast clearance from human body by reticuloendothelial system (RES) and limited intracellular uptake to target cell. In this study, polyethylenglycol (PEG)-incorporated cationic liposomes were prepared by ionic complexation of positively charged liposomes with carboxylated polyethyleneglycol (mPEG-COOH). The cationic liposomes had approximately $98.6{\pm}1.0nm$ of mean particle diameter and $42.8{\pm}0.8mV$ of zeta potential value. The PEG-incorporated cationic liposomes had $110.1{\pm}1.2nm$ of mean particle diameter with an increase of about 10 nm compared to the cationic liposomes. Zeta potential value of them was $12.9{\pm}0.6mV$ indicating 30mV decrease of cationic charge compared to the cationic liposomes. The amount of PEG which was incorporated onto the cationic liposomes was assayed by using picrate assay method and the incorporation efficiency was $58.4{\pm}1.1%$. Loading efficiency of model drug, doxorubicin, into cationic liposomes or PEG-incorporated cationic liposomes was about $96.0{\pm}0.7%$. Results of intracellular uptake which were evaluated by flow cytometry analysis of doxorubicin loaded liposomes showed that intracellular uptake of PEG-incorporated cationic liposomes was higher than the cationic liposomes or DSPE-mPEG liposomes. In addition, cytotoxicity of PEG-incorporated cationic liposomes was comparable to cationic liposomes. Consequently, the PEG-incorporated cationic liposomes of which surface was incorporated with PEG by ionic complex may be applicable as anticancer drug carriers that can increase therapeutic efficacy.

• Polymer(Korea)
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• v.28 no.6
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• pp.502-508
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• 2004

Cationic liposomes for cancer treatment have been developed in the field of chemotharpy. It was well combined on the surface of anionic tumor cell membrane by electrostatic interaction. Thus, the object of this study was to prepare the cationic liposomes capable of forming an ionic complex with the anionic cell membrane. To prepare the cationic liposomes, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE) as a cationic lipid material and polyethylenimine (PEI) as a cationic polymer were synthesized. Ionic property on the surface of liposomes was determined by the zeta potential. The adsorption characteristics of plasma protein for liposome in bovine serum were determined by the particle size and turbidity change. To estimate the stability of liposome in buffered solution, the change of particle size was measured at room temperature for seven days. The cationic liposomes were absorbed a large amount of plasma protein in bovine serum because plasma protein having anionic charge was fixed on the surface of cationic liposomes. This result indicate that the modification on the surface of liposomes using cationic polyethylenimine enhances the protein adsorption in bovine serum. Additionaly, cationic liposomes showed good stability in buffered solution for seven days.

• Journal of Pharmaceutical Investigation
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• v.39 no.5
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• pp.339-343
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• 2009

Recently, co-delivery of drug and gene has been attempted for higher therapeutic effects of anticancer agents. In this study, cationic liposomes were prepared using 1,2-dioleoyl-3-trimethylammoniopropane (DOTAP) as a cationic lipid to investigate the effect of drug loading on the physicochemical characteristics of cationic liposomes/DNA complexes. The complex formation between cationic liposomes and negatively charged plasmid DNA was confirmed and the protection from DNase was observed. Particle size of complexes was reduced not by drug loading, but by the increased ratio of cationic lipid to plasmid DNA. Meanwhile, zeta potential of complex was increased by the addition of cationic liposomes to complexes and the effect of drug loading on the zeta potential was not much higher than on particle size. Gel retardation of complexes was indicated when the complexation weight ratios of cationic lipid to plasmid DNA were higher than 24:1 for drug free complexes and 20:1 for drug loaded ones, respectively. Agarose gel retardation showed the similar complexation between plasmid DNA and drug free liposomes or drug loaded liposomes. Both complexes protected plasmid DNA from DNase independent of complexation temperature. From the results, drug loading may affect not the complex formation of cationic liposomes and plasmid DNA, but the particle size of complex.

• Journal of Pharmaceutical Investigation
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• v.40 no.6
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• pp.357-362
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• 2010

To enhance therapeutic effects of insulin-sensitizing adipokine, ADN gene and potent agonists, rosiglitazone for the $PPAR{\gamma}$, cationic liposomes as non-viral vectors were formulated. The particle size and zeta potential of drug loaded and unloaded cationic liposomes were investigated. The complex formation between cationic liposomes and negatively charged plasmid DNA was confirmed and the protection from DNase was observed. In vitro transfection was investigated in HepG2, HeLa, and HEK293 cells by mRNA expression of ADN. Encapsulation efficacy of rosiglitazone-loaded liposomes was determined by UV detection. Particle sizes of cationic liposomes were in the range of 110-170 nm and those of rosiglitazone-loaded cationic liposomes were in the range of 130-180 nm, respectively. Gel retardation of complexes indicated that the complex was formed at weight ratios of cationic lipid to plasmid DNA higher than 20:1. Both complexes protected plasmid DNA from DNase either drug free or drug loading. Encapsulation efficiency of rosiglitazone-loaded emulsion was increased by drug dose. The mRNA expression levels of ADN were dose-dependently increased in cells transfected with plasmid DNA. Therefore, cationic liposomes could be potential co-delivery system for drug and gene.

• Journal of Pharmaceutical Investigation
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• v.39 no.5
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• pp.333-337
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• 2009

We aimed to optimize the formulation of porcine placental extract (PPE)-loaded liposomes for intramuscular administration and to investigate the effect of surface charges on the muscular retention in mice. PPE-loaded liposomes were formulated to have neutral, anionic, or cationic surface charges. The in vitro release profiles were studied by spectrofluorometry. In vivo distribution patterns at mice were studied using molecular imaging technology. Among the three types of liposomes, 1,2-dioleoyl-3-trimethylammonium-propane and 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-based cationic liposomes showed the most prolonged in vitro release profile. Consistent with the in vitro results, the in vivo distribution study revealed that the cationic liposomes were retained at the site of administration for the longest period. Our results suggest the potential of cationic PPE-loaded liposomes for sustained release of the components after intramuscular administration.

• Bulletin of the Korean Chemical Society
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• v.34 no.3
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• pp.931-935
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• 2013

Lipid events in liposome-mediated transfection (lipofection) are largely unknown. Here we studied whether phospholipase D (PLD), an important enzyme responsible for phospholipid breakdown, was affected during lipofection of HepG2 cells with a luciferase plasmid. Synthetic cholesterol (Chol) derivatives, including $3{\beta}$[L-ornithinamide-carbamoyl]Chol, [polyamidoamine-carbamoyl]Chol and $3{\beta}$[N-(N',N'-dimethylaminoethane)-carbamoyl]Chol, and a cationic lipid, N-[1-(2,3-dioleyloxy)propyl]-N,N,N-trimethylammonium chloride were mixed with a helper lipid dioleoylphosphatidylethanolamine to form respective cationic liposomes. All cationic liposomes were found to stimulate PLD. Although orders of magnitude effects of the cationic liposomes on PLD stimulation did not consistently match those on cytotoxicity and luciferase expression, a causal relationship between PLD activation and cytotoxic effect was remarkable. PLD stimulation by the cationic liposomes was likely due to their amphiphilic characters, leading to membrane perturbation, as supported by similar results obtained with other membrane-perturbing chemicals such as oleate, melittin, and digitonin. Our results suggest that lipofection induces cellular lipid changes such as a PLD-driven phospholipid turnover.

• Journal of Pharmaceutical Investigation
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• v.40 no.6
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• pp.353-356
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• 2010

Although liposomes have been applied as drug delivery systems in various fields, the usage was limited due to the low encapsulation efficiency compared to other carrier systems. Here, cationic liposomes were prepared by mixing 1,2-dioleoyl-3-trimethylammoniopropane (DOTAP) as a cationic lipid, 1,2-dioleoyl-sn-glycerol-phosphoethanolamine (DOPE) and cholesterol (CH), and the liposomes were hydrated by varying the aqueous phases such as phosphate-buffered saline (PBS), 5% dextrose, and 10% sucrose in order to improve the encapsulation efficiency of bovine serum albumin (BSA). The particle size and zeta potential were determined by dynamic light scattering method and in vitro release patterns were investigated by spectrophotometry. Particle size and zeta potential of liposomes were varied depending on the ratio of DOTAP/DOPE/CH in range of 270-350 nm and 0.8-9.7 mV, respectively. Moreover, the addition of polyethylene glycol (PEG) improved the encapsulation efficiency from 37% to 43% as well as reduced particle sizes of liposomes while the liposomes were hydrated in PBS. When the liposomes were hydrated with 10% sucrose, the encapsulation efficiency of BSA was higher than any other groups. Whereas PBS was used as hydration solution, lower encapsulation efficiency was obtained compared with other groups. More than 60% of BSA was released from the liposomes hydrated with 10% sucrose; thereafter another 20% of BSA was released. Therefore, release pattern of BSA from cationic liposomes was extended release in this study. From the results, cationic liposomes dispersed in 10% sucrose would be potential carrier with high encapsulation efficiency.

• Journal of Pharmaceutical Investigation
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• v.38 no.3
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• pp.163-169
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• 2008

Liposomes are spherical vesicles composed of lipid bilayer membranes. However, the conventional liposomes have been found to be plagued by rapid opsonization and taken up by the reticuloendothelial system (RES), resulting in shortened circulation time and limited intracellular uptake to target cell. In this study, polyethyleneglycol-cationic liposomes (PCL) containing cationic lipid and DSPE-mPEG were prepared by thin film cast-hydration method. The PEG liposomes had approximately $97.0{\pm}1.3\;nm$ of mean particle diameter and $-21.7{\pm}1.2\;mV$ of zeta potential value. PCL had $96.4{\pm}1.8\;nm$ of mean particle diameter and $-8.7{\pm}1.1\;mV$ of zeta potential value with a decrease of about 10 mV compared to the PEG liposomes. Loading of model drug, doxorubicin (DOX), in liposomes were carried out by using remote loading method and the loading efficiency of DOX in liposomes was about $95.0{\pm}1.9%$. Intracellular uptake and cytotoxicity of PCL were higher than that of PEG liposomes to murine B16F10 melanoma cells. In addition, anti-tumor activity of PCL was similar to that of PEG liposomes on growth of A549 human lung carcinoma in BALB/c mice. Consequently, PCL modified with cationic lipid may be applicable as anticancer drug carriers that can increase intracellular uptake and therapeutic efficacy.

• Applied Chemistry for Engineering
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• v.26 no.2
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• pp.165-172
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• 2015

Quercetin and its glycoside, rutin, are flavonoids, which are well known as natural antioxidants. In this study, cationic liposomes loaded with flavonoids (quercetin or rutin) were investigated for their effects on cell and skin permeability, and protective effects against UVA. The particle size of the empty cationic liposomes was in the range of 100~130 nm, and the zeta potential was + 33.05 mV. The entrapment efficiency of 0.5R/CL was higher than that of 0.5 Q/CL. The cellular uptake of the cationic liposomes was five-fold higher than that of liposomes. The skin permeability of quercetin and rutin was investigated using Franz diffusion cells. Compared to the initial loading dose, the amount of quercetin or rutin delivered to the skin by cationic liposomes was higher than that delivered by conventional liposomes or phosphate-buffered saline. From the protective effect of cationic liposomes against UVA ($25J/cm^2$), we found that the cell viability in cationic liposomes containing flavonoids was higher than that of using UVA irradiation only. These results indicate that cationic liposomes provide enhanced delivery of flavonoids (quercetin and rutin) into the skin and may be used for antiaging and antioxidant cosmetics.

• Journal of Pharmaceutical Investigation
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• v.28 no.2
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• pp.93-98
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• 1998

We have developed liposomes which can be easily prepared with inexpensive lipid, have enhanced stability, and can efficiently deliver DNA into the COS-l cells, Liposome formulations were prepared using cationic materials such as dimethyldioctadecyl ammonium bromide (DDAB), cetyltrimethyl ammonium bromide(CTAB), We investigated the effect of cationic liposome formulations on in vitro DNA transfection, DDAB-containing liposomes showed increased transfection efficiency which was 3.2-fold as much as that by $Lipofectin^{\circledR}$, but CTAB-containing liposomes were inactive in gene transfection. The effect of colipid of DDAB-containing liposome was also investegated. As a colipid, dioleylphosphatidylethanolamine(DOPE) and cholesterol did altered the transfection efficiency of DDAB-containing liposomes. And increased DDAB concentration lowered the transfection efficiency. The optimum amount of liposomal formulation was $10\;{\mu}M$ for $1\;{\mu}g$ of DNA. In the experiment of stability, DOPE-containing liposomes formulation showed a broad size distribution and separation of two major peaks on a 5th day of preparation, but liposomes containing cholesterol was stable for 10 days. DDAB-containing liposomal DNA delivery system was prepared easily and was stable.