• Journal of Pharmaceutical Investigation
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• 제38권4호
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• pp.255-259
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• 2008

The present study aimed to investigate the in-vitro characteristics of N4-amino acid derivatives of cytarabine for the oral delivery of cytarabine. After the synthesis of L-Ile-cytarabine, L-Leu-cytarabine and L-Arg-cytarabine, the gastrointestinal stability of each prodrug was examined using artificial gastric juice and intestinal fluids. The cellular uptake characteristics of prodrugs were also examined in Caco-2 cells. While L-Ile-cytarabine and L-Leu-cytarabine appeared to be stable in all the tested biological media during 4-hr incubation, L-Arg-cytarabine was rapidly disappeared within 5 min. Accordingly, the cellular uptake of L-Ile-cytarabine and L-Leu-cytarabine was significantly higher than that of its parent drug, cytarabine in Caco-2 cells but the cellular uptake of L-Arg-cytarabine was similar to that from its parent drug. The cellular uptake of L-Ile-cytarabine and L-Leu-cytarabine appeared to be saturable as drug concentration increased from 0.4 to 4 mM. Collectively, L-Ile-cytarabine and L-Leu-cytarabine could be promising candidates to improve the oral absorption of cytarabine via a saturable transport pathway.

• Archives of Pharmacal Research
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• 제16권2호
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• pp.123-128
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• 1993

The surface of cyarabine-entrapped albumin microspheres, the surface modified albumin microspheres hsowed remakably incrased hydrophilicity, good dispersability in aqueous medium and reduced aggregation during storage which met the requirements of injectable drug carriers in acqueous vehicle. In vitro cytarabine release from hydrophilic albumin microspheres (HAM) was a function of the cytarabine to albumin ratio, whereas no significant difference in the releasing capacity was obnserved between surface modified HAM within the small size range$(2\;to\;5\mu{m)}$ studied. HAM containing 15-23% drug were gradually degraded by protease and continuously released up to 60% of the total entrapped cytarabine for 6h. These results thus suggest that HAM is a suitable cytarabine carrier which may be injected intraveneously with the benefits of a reduced risk of blood embolism induced by aggregates and prolonged cytarabine release.

• 한국임상약학회지
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• 제8권1호
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• pp.59-67
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• 1998

The stability of cytarabine (manufactured by two pharmaceutical companies) in intravenous admixture and in plastic syringe was investigated. The admixures containing cytarabine 0.35, 8.6, and 17.1 mg/ml in $0.9\%\;NaCl\;or\;5\%$ D5W were placed in PVC bags or glass bottles, and the reconstituted cytarabine (50 mg/ml) was placed in plastic syringe. One ml aliquots were withdrawn immediately after each preparation and stored at $4^{\circ}C\;or\;24^{\circ}C$ for 1, 2, 4, 6, 8, 10, and 14 days unprotected from light. Each sample was tested for pH and visually inspected for precipitation and change in color. Cytarabine concentrations were measured using high-performance liquid chromatography. Neither precipitation nor change in color was noted, and there were no change in pH during 14 days of testing. The changes in cytarabine concentrations were less than $10\%$. In conclusion, cytarabine in IV admixture or plastic syringe was stable for at least 14 days at $4^{\circ}C\;and\;24^{\circ}C.$(Kor. J. Clin. Pharm. 1998; 8(1): 59-67)

• 약학회지
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• 제44권1호
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• pp.66-70
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• 2000

This study was designed to examine the effect of Mori cortex radicis extract on cytarabine induced alopecia in young rat. cytarabine (50 mg/kg) was injected to Eight-day-old rats everyday for 7 days. After the injection, Mori cortex radicis extract was spread on the alopecia young rats for 12 days topically. The stimulative effect of hair growth was observed on 12th day of topical application. The stimulative effect of hair growth was best in MeOH extract group. And the same result was obtained in the experiment of hair follicle cross section.

• 약학회지
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• 제32권6호
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• pp.371-376
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• 1988

The effect of polysorbate 40, used as a surfactant during the process of manufacture, on the properties of cytarabine microspheres with carnaubu wax was studied. It was revealed that the mean particle size increased in proportion to the concentration of polysorbate 40, and that the dissolution rate of the cytarabine from the microspheres decreased greatly more than the cytarabine powder only, but increased in proportion to the concentration of polysorbate 40 as surfactant.

• Archives of Pharmacal Research
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• 제10권2호
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• pp.75-79
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• 1987

Liposomes were studied as a drug delivery system. Multilamellar vesicles, small unilamellar vesicles and large unilamellar vesicles containing cytarabine were prepared using egg yolk lecithin and cholesterol. Large unilamellar vesicles showed the highest encapsulation efficiency of all and their encapsulation efficiency increased as the buffer volume decreased. Cholesterol increased the stability of liposomal drug products as drug carriers and reduced the permeability of drug across the liposomal membrane. The release rate of cytarabine increased with incubation temperature and decreased with cholesterol incorporation in liposomal membrane. The release mechanism of cytarabine from large unilamellar vesicles in vitro was chiefly due to simple diffusion across the liposomal membrane rather than liposomal rupture.

• Journal of Pharmaceutical Investigation
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• 제22권4호
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• pp.323-326
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• 1992

$Poly({\varepsilon}-carbobenzoxy\;L-lysine)/poly(ethylene oxide)/poly({\varepsilon}-carbobenzoxy\;L-lysine)$ (LEL) block copolymers containing $poly({\varepsilon}-carbobenzoxy\;L-lysine)$ (PCLL) as the A component and poly(ethylene oxide) (PEO) as the B component were investigated as drug delivery matrix. PCLL homopolymer and LEL block copolymer microspheres containing anticancer drug, cytarabine, were prepared by a solvent evaporation process and the release patterns of cytarabine from the microspheres were investigated in vitro. The size of PCLL homopolymer and LEL block copolymer microspheres was ranged from $0.2\;{\mu}m$ to $1\;{\mu}m$ in diameter and the shape of the microspheres was almost round. The release pattern of cytarabine from the block copolymer microspheres was dependent on the mole % of PEO of the block copolymers.

• Archives of Pharmacal Research
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• 제9권1호
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• pp.39-43
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• 1986

Bovine serum albumin microspheres containing cytarabine were prepared using cross-linking agent, formaldehyde. The shape and the size distribution of them were observed. The shape of them was spherical and the susrface was compact and smooth. The size distribution of them was affected by dispersion forces during emulsfication. The release of cytarabine from albumin microspheres was dependent upon cross-linking time, amount of cross-linking agent and drug/albumin ratio. However, the difference of drug release by the dispersion forces was not great. After release test, the shape of albumin microspheres was nonspherical and the albumin matrix seemed to be a little relaxed. The degradation tests of albumin microspheres by the proteolytic enzyme showed that albumin microspheres were progressively digested according to the cross-linking degree.

• Archives of Pharmacal Research
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• 제9권2호
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• pp.87-91
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• 1986

In attempt to develop a drug delivery system using serum albumin microspheres, bovine serum albumin microspheres containing antitumar agent. Cytarabine, were prepared. The shape, surface characteristics, size distribution, behavior of in vivo distribution, drug release behavior, and degradation of albumin microsphers in animal liver issue homogenate and proteolytic enzyme were investigated. The shape of albumin microspheres was spherical and the surface was smooth and compact. The size distribution of the albumin microspheres was effected by dispertion forces during emulsification and albumin concentration. Distribution of albumin microspheres after imtravenous administration in rabbit was achieved immediately. In vitro, albumin microsphere matrix was so hard that it retained most of cytarabine except initial burst during the first 10 minutes, and the level of drug release during the initial burst was affected by heating temperature, drug/albumin microsphere matrix was so hard that it retained most of cytarabine except initial burst during the first 10 minutes, and the level of drug release during the initial burst was affected by heating temperature, drug/albumin concentration ratio and size distribution. After drug release test, the morphology of albumin microspheres was not changed. Albumin microsphere matrix was degraded by the animal liver issue homogenate and proteolytic enzyme. The degree of degradation was affected by heating temperature.

• 한국잠사곤충학회지
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• 제42권2호
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• pp.83-85
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• 2000

This study was carried out to investigate the hair growth effect of Mori cortex radicis mixture on the hair of rat. Cytarabine(50mg/kg) was injected to eight-day-old rats for 7 days. When the mixture of Mori cortex radicis was administered to the rat by route of skin, it promoted the growth of hair. These data suggest that Mori cortex radicis mixture have an effect on the hair growth in cytarabine-induced alopecia rat.