• Biotechnology and Bioprocess Engineering:BBE
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• v.6 no.4
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• pp.284-288
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• 2001

Lipid emulsions with saturated triacylglycerols (TAGs) with 4 to 10 carbons in each acyl chain were prepared to study how the oil component alters the stability of the lipid emul-sions when phosphatidylcholines were used as emulsifiers. The average droplet size of the emul-sions became smaller as the chain length of the TAG increased. For a given oil emulsion with smaller droplets was formed with an emulsifier having higher HLB value. The influence of HLB values on the droplet size was biggest for the tributyrin (C4) emulsion. For the tricaprylin(C8) emulsions, droplet size was identical at given emulsifier concentrations regardless of HLB values. The HLB value and the concentration of the emulsifiers also affect the droplet size of the emul-sions. The emulsions with smaller average droplet size were more stable than with bigger size for 20 days. The oil and water (o/w) interfacial tension in inversely proportional to the initial droplet size of the emulsion.

• Journal of Pharmaceutical Investigation
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• v.31 no.3
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• pp.167-172
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• 2001

All-trans retinoic acid (ATRA), vitamin A acid, has been shown to exert anticancer activity in a number of types of cancers, particularly in acute promyelocytic leukaemia (APL). Due to its highly variable bioavailability and induction of its own metabolism after oral treatment, development of parenteral dosage forms are required. However, its poor aqueous solubility and chemical unstability give major drawbacks in parenteral administration. This study was undertaken to investigate a possibility to develop a parenteral formulation of ATRA by employing solid lipid nanoparticle (SLN) as a carrier. By optimizing the production parameters and the composition of SLNs, SLNs with desired mean particle size (<100 nm) as a parenteral dosage form could be produced from trimyristin (as solid lipid), Egg phosphatidylcholine and Tween 80 (as SLN stabilizer). The mean particle size of SLN formulation of ATRA was not changed during storage, suggesting its physical stability. Thermal analysis confirmed that the inner lipid core of SLNs exist at solid state. The mean particle size of ATRA-loaded SLNs was not significantly changed by the lyophilization process. ATRA could be efficiently loaded in SLNs, while maintaining its anticancer activity against HL-60, a well-known APL cell line. Furthermore, by lyophilization, ATRA loaded in SLN could be retained chemically stable during storage. Taken together, our present study demonstrates that physically and chemically stable ATRA formulation adequate for parenteral administration could be obtained by employing SLN technology.

• Journal of Pharmaceutical Investigation
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• v.41 no.5
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• pp.295-300
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• 2011

Paclitaxel is a well known anticancer agent and has been a pharmaceutical challenge because of its extremely poor water-solubility and susceptibility to the p-glycoprotein (p-gp)-mediated efflux in multi-drug resistant (MDR) cancer cells. Tributyrin (TB), a triglyceride with relatively short fatty acid chains, was chosen as solubilizing vehicle for paclitaxel based on the solubility study (26.6 mg/mL). Tributyrin (10%) o/w emulsion containing paclitaxel (5%), egg phosphatidylcholine (5%) and pegylated phospholipid (0.5%) was prepared by high pressure homogenization to obtain submicron-sized emulsion. The mean particle size of the resultant TB emulsion was 395.5 nm. Paclitaxel in TB emulsion showed higher anticancer activity against human breast cancer cell line, MCF-7, than free form delivered in DMSO solution. On the other hand, its anticancer activity was significantly reduced in MCF-7/ADR, a MDR variant cancer cell line of MCF-7, and recovered by the presence of verapamil, suggesting of the susceptibility to the p-gp mediated efflux even though paclitaxel was encapsulated into emulsion. The TB emulsion showed great potential as a promising vehicle for water-insoluble anticancer agent, paclitaxel.

• Journal of Pharmaceutical Investigation
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• v.40 no.1
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• pp.39-43
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• 2010

Solid lipid nanoparticles (SLNs) were freeze-dried to obtain a stable solid dosage form with the aid of various cryoprotectants such as trehalose, sucrose, glucose, fructose, and glycerol. Tricaprin(TC) and trilaurin(TL) were used as lipid matrices for SLNs and stabilizers were egg phosphatidylcholine and pegylated phospholipid. All cryoprotectants tested did not cause changes in mean particle size of SLNs when mixed with SLNs before freeze-drying. However, the mean particle sizes of reconstituted SLNs after freeze-drying were significantly different from those of the un-lyophilized original SLN dispersions depending on the types and concentration of cryoprotectants. Although the freeze-dried SLNs without any cryoprotectants were easily reconstituted by hand-shaking, the mean particle size drastically increased (> $8\;{\mu}m$ for TC SLNs and around $1\;{\mu}m$ for TL SLNs) compared to that of un-lyophilized original dispersion (97 nm for TC SLNs and 164 nm for TL SLNs). Trehalose and sucrose were the most effective additives to protect the SLNs during lyophilization. The reconstituted SLNs were physically stable for 24 hours when lyophilized with 12.5% trehalose, sucrose, glucose, fructose or glycerol.

• Korean Journal of Veterinary Research
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• v.33 no.1
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• pp.137-143
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• 1993

This study was carried out to completelycure the experimental bovine theileriasis with small unilamella vesicle liposome incorporated buparvaquone which was effective both to schizonts in lymphocyte of lymph nodes and piroplasmic stage in erythrocytes. Small unilamella vesicle liposome incorporated buparvaquone was prepared by French pressure cell method using egg phosphatidylcholine. The diameter of the vesicles was ranged from 5 to 220 nm, but the most vesicles were ranged from 10 to 50 nm in diameter. The incorporation rate for buparvaquone was 100%. Parasitaemia of the 10 calves inoculated with $5{\times}10^8$ erythrocytes infected with Theileria sergenti were first detected from on day 16 to day 23 after inoculation. In calves treated with a dose rate 2.5 mg/kg BW of free buparvaquone, a gradual decrease in piroplasmic parasitaemia was observed following treatment to day 5. However parasitaemia levels returned to near pretreatment values after approximately 60 days. In calves treated with a dose rate 5.0mg/kg BW of free buparvaquone, parasitaemia were disappeared on day 3 after treatment, but there was a mild recrudescence of infection on day 28 after treatment. In calves treated intraavenously with a dose rate 2.5 mg/kg BW of buparvaquone incorporated in liposome, the calves were all cured on day 2 or day 3 after treatment. In calves treated subcutaneously and intraperiotoneally with a dose rate 2.5 mg/kg BW of buparvaquone incorporated in liposome, parasitaemia were disappeared on day 3 or day 4 after treatment, but there was a mild recrudescence of infection on day 40 or day 45 after treatment.

• Bulletin of the Korean Chemical Society
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• v.22 no.9
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• pp.979-983
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• 2001

Thermoanaerobacter ethanolicus is a strictly anaerobic and thermophilic bacterium whose optimum temperature ranges over $65-68^{\circ}C.$ T. ethanolicus was known to contain a bipolar very long chain fatty acyl component such as $\alpha$, $\omega-1316-dimethyloctacosanedioate$, as one of the major membrane components. However, exact physiological role of this unusual component in the membrane remains unknown. Such a very long chain fatty acyl component, $\alpha$, ${\omega}-1316-dimethyloctacosanedioate$, dimethyl ester (DME C30), was isolated, and purified from the membrane of T. ethanolicus. As a function of added concentrations of the $\alpha$, $\omega-1316-dimethyloctacosanedioate$, dimethyl ester (DME C30) or cholesterol into the standard liposomes, the acyl chain ordering effect was investigated by the steady-state anisotropy with 1,6-diphenyl-1,3,5-hexatriene (DPH) as a fluorescent probe. Acyl chain order parameter (S) of vesicles containing DME C30 is higher comparing with phosphatidylcholine (PC) only vesicles. This result was discussed thermodynamically with the aid of the simulated annealing molecular dynamics simulations. Through the investigation of all the possible conformational changes of DME C30 or cholesterol, we showed that DME C30 is very flexible and its conformation is variable depending on the temperature comparing with cholesterol, which is rigid and restricted at overall temperature. We propose that the conformational change of DME C30, not the configurational change, may be involved in the regulation of the membrane fluidity against the changes of external temperature.