• Journal of Pharmaceutical Investigation
• /
• v.39 no.5
• /
• pp.339-343
• /
• 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
• /
• v.40 no.6
• /
• pp.357-362
• /
• 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.

• 한국생물공학회:학술대회논문집
• /
• 2000.11a
• /
• pp.755-758
• /
• 2000

Glucose sensitive liposomes-amino acid cinjugates Were prepared by DPPC and asparagine derivatives. Liposomes(amino acid added) have higher glucose binding affinity than liposome(amino acid non-added) or distilled water. The liposomes stabilily were increased by adding cholesterol. Liposomes(cholesterol non-added) particles size were bigger than cholesterol added liposomes.

• Journal of the Society of Cosmetic Scientists of Korea
• /
• v.22 no.2
• /
• pp.99-114
• /
• 1996

The MLV liposomes have been developed in many drugs and cosmetics fields. The phospholipid base is made from ceramides, cholesterol, cholesteryl ester, lecithin, lanolin ester, and B-sitosterol, and surfactants are made by using (PEG)n-sitosterol(n=5) and K-cetyl phosphate. We made visicles stable by passing samples through Microfludizer and croated multilamellar vesicles to make MLV liposomes similar to the structure of men's skin. In order to make MLV liposomes, we created lipid membrane films which a mixure of phospholipid base and polyol group was reacted above Tc(95$^{\circ}C$) by gelation for 3 hours. As the optimum conditions of Microfluidizer, we figured out 700 bar for the passing pressure of samples, 4$0^{\circ}C$ for its temperature, and 3 times of frequency to pass through samples. Our MLV liposomes is stable on conditions of a low temperature(5$^{\circ}C$) and a high temperature(45$^{\circ}C$), which is not to be split in a large range. We produced our own moisturizing cream which has a good affinity to skin by means of this system.

• Bulletin of the Korean Chemical Society
• /
• v.23 no.1
• /
• pp.93-97
• /
• 2002

Poly(ethylene glycol)-phosphatidylethanolamine conjugate (PEG-PE) has been used in preparing longcirculating liposomes. As a substitute for PEG-PE which can also be used in the long-circulating liposome formualtions, but can be prepared more readily with a lower cost, PEG-Phe-Chol was synthesized from PEG, phenylalanine, and cholesterol. The addition of the PEG derivative to distearoylphosphatidylcholine (DSPC) led to the formation of mixed micelles as well as liposomes when the derivative content was 10 mol% or greater. On the other hand, the addition of just 5 mol% PEG-Phe-Chol to dioleoylphosphatidylethanolamine (DOPE) generated mixed micelles as well as liposomes, but the formation of mixed micelles was completely inhibited by the addition of cholesterol. The leakage of entrapped calcein out of DOPE/cholesterol (7/3) liposomes containing 5 mol% PEG-Phe-Chol was about 45% during the incubation time for 24 h in 50% rabbit plasma, which was similar to that of the same liposomes containing 5 mol% PEG-dipalmitoylphosphatidylethanolamine (DPPE) under the identical conditions.

• YAKHAK HOEJI
• /
• v.42 no.3
• /
• pp.274-274
• /
• 1998

Aclarubicin(ACL)-entrapped freeze dried liposomes were prepared using Microfludizer to attain a sustained release at targeted organs in a prolonged time so that it can reduce th e side effect and maximize the therapeutic effect. The freeze-dried liposomes were evaluated for pharmacokinetics, antitumor activity against Sarcoma 180, cytotoxicity against L1210 and A549 tumor cells, spleen toxicity and myelosuppressive action. The AUC0->8hr values were 122+/-42, 382+/-140, 419+/-171, 835+/-206 and 443+/-309mcg min/ml for free ACL. ACL-liposome formulation I, II, III and IV, respectively. Cytotoidcity of ACL-entrapped liposomes against L1210 and A549 tumor cells was 2-4 times higher than that of free aclarubicin. ACL-liposome formulation I(PC/CHOL/TA) showed the most potent antitumor activity against Sarcoma 180 in mice. The loss of body weight was much smaller with ACL-entrapped liposomes than free ACL after I.p. injection at a dose of 2 mg/kg/day. Compared to free ACL, ACL-entrapped liposomes expressed a lower and delayed spleen toxicity up to 5th day after I.v. administration. Myelosupperssion seemed to be lower with ACL-entrapped liposome of PC/PC-hydrate/CHOL/TA (formulation III) than free aclarubicin.

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

• Food Science and Biotechnology
• /
• v.14 no.5
• /
• pp.604-607
• /
• 2005

In this study, the effect of ${\beta}$-sitosterol (SS) in the liposome bilayer on the stability of incorporated retinol was evaluated. Retinol was incorporated into liposomes consisting of various ratios of soybean phoaphatidylcholine (PC) to SS, while liposomes were prepared as multilamellar vesicles by the dehydration/rehydration method. Retinol was readily incorporated into liposomes with various SS contents, with incorporation efficiencies higher than 98% for all conditions. The incorporation efficiency of retinol increased slightly as the SS content in liposomes increased. Its average particle size also increased as the SS content increased. Mean particle size at PC to SS ratios of 100:0, 90:10, 80:20, 70:30, 60:40, and 50:50 were 12.16, 17.57, 35.00, 40.62, 83.45, and $88.94\;{\mu}m$, respectively. Liposomal retinol degradation in aqueous solution was measured with respect to SS content at various periods of time at four different temperatures of 4, 25, 37, and $50^{\circ}C$, and the stability of the incorporated retinol enhanced as the SS content increased. At $4^{\circ}C$, for example, retinol in the liposomes of 50:50 (PC:SS) remained at 84.42% after storage for 10 days, while in 100:0 (PC/SS) it remained at 42.62%. These results indicate that SS content in liposomes played an important role in the incorporation efficiency of retinol and its stability.

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

• Journal of Pharmaceutical Investigation
• /
• v.30 no.1
• /
• pp.39-45
• /
• 2000

We have investigated the efficacy of liposome encapsulated N-(phosphonacetyl)-L-aspartic acid (PALA) for the treatment of the C-26 murine colon tumor in Balb/c mice, and have compared it in this regard to free PALA. Healthy female Balb/c mice and C-26 tumor inoculated mice were randomized for the maximum tolerated dose (MTD) study and the in vivo therapy study, and the survival was measured after a single intraperitoneal injection of the drug. The maximum tolerated dose for intraperitoneally administered drug was found to be 750 mg/Kg for free PALA, and was greater than the maximum dose possible (150 mg/Kg) for PALA encapsulated in both DSPC and DSPG liposomes. When drug was administered one day after tumor implantation, 150 mg/Kg of PALA in DSPG liposomes increased the percentage of tumor bearing mice surviving at day 36 from 8% (buffer control) to 88%. In contrast, 150 mg/Kg free PALA increased the day 36 surviving percentage to only 25%. A 150 mg/Kg dose of PALA in DSPC liposomes increased the surviving percentage to 50%, while a 75 mg/Kg dose of PALA in sterically stabilized liposomes increased the surviving percentage to 78%. These results show that PALA in negatively charged or sterically stabilized liposomes can exhibit considerably greater potency than free PALA in C-26 tumor bearing mice.