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Prolonged blood circulation of methotrexate by modulation of liposomal composition.

Prolonged circulation by liposomal incorporation has been shown to enhance the therapeutic efficacy of drugs in many cases. The purpose of this study was to investigate whether the prolonged circulation of methotrexate (MTX) can be achieved by modulating the liposomal compositions. Various compositi... Full description

Journal Title: Drug delivery 2001 Oct-Dec, Vol.8(4), pp.231-237
Main Author: Hong, M S
Other Authors: Lim, S J , Lee, M K , Kim, Y B , Kim, C K
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: ISSN: 1071-7544
Link: http://search.proquest.com/docview/72331104/?pq-origsite=primo
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title: Prolonged blood circulation of methotrexate by modulation of liposomal composition.
format: Article
creator:
  • Hong, M S
  • Lim, S J
  • Lee, M K
  • Kim, Y B
  • Kim, C K
subjects:
  • Animals–Administration & Dosage
  • Antineoplastic Agents–Blood
  • Blood Circulation–Pharmacokinetics
  • Cholesterol–Administration & Dosage
  • Chromatography, High Pressure Liquid–Blood
  • Drug Carriers–Pharmacokinetics
  • Drug Stability–Pharmacokinetics
  • Liposomes–Pharmacokinetics
  • Methotrexate–Pharmacokinetics
  • Particle Size–Pharmacokinetics
  • Phosphatidylcholines–Pharmacokinetics
  • Polyethylene Glycols–Pharmacokinetics
  • Rats–Pharmacokinetics
  • Rats, Sprague-Dawley–Pharmacokinetics
  • Time Factors–Pharmacokinetics
  • Tissue Distribution–Pharmacokinetics
  • Antineoplastic Agents
  • Drug Carriers
  • Liposomes
  • Phosphatidylcholines
  • Polyethylene Glycols
  • Cholesterol
  • Methotrexate
ispartof: Drug delivery, 2001 Oct-Dec, Vol.8(4), pp.231-237
description: Prolonged circulation by liposomal incorporation has been shown to enhance the therapeutic efficacy of drugs in many cases. The purpose of this study was to investigate whether the prolonged circulation of methotrexate (MTX) can be achieved by modulating the liposomal compositions. Various compositions of liposomes were prepared with 2:1 of phosphatidylcholine (PC) and cholesterol (CH) with or without distearoylphosphatidyl-ethanolamine-N-poly(ethyleneglycol) 2000 (DSPE-PEG). The MTX encapsulation efficiency depended on the type of PC used. It also appeared to increase by inclusion of DSPE-PEG. The size of liposomes decreased by the inclusion of DSPE-PEG. The inclusion of DSPE-PEG lowered the plasma-induced release of MTX from EggPC/CH and DPPC/CH liposomes, suggesting its enhancement effect on the liposomal stability. After intravenous injection to rats, the pharmaockinetics and biodistribution of MTX were significantly changed by liposomal incorporation and also by the composition of liposomes. The total body clearance of MTX incorporated in EggPC/CH, DPPC/CH, EggPC/CH/DSPE-PEG, and DPPC/CH/DSPE-PEG liposomes decreased 4.4-, 14.9-, 24.5-, and 53.1-fold, compared with that of free MTX. The ratio of MTX concentration in blood to liver and spleen after injection of DPPC/CH, EggPC/CH/DSPE-PEG, and DPPC/CH/DSPE-PEG liposomes was 5.4-, 8.5-, and 13.5-fold higher than that of EggPC/CH liposomes. Furthermore, the accumulation of MTX in the kidney, one of the organs in which MTX exhibits its toxicity, was significantly lowered by liposomal incorporation, especially by DSPE-PEG-containing liposomes. Taken together, DPPC/CH/DSPE-PEG liposomes most effectively prolonged the blood circulation, and reduced hepatosplenic and kidney uptake of MTX. DPPC/CH/DSPE-PEG liposomes may have potential as an efficient delivery system for MTX.
language: eng
source:
identifier: ISSN: 1071-7544
fulltext: fulltext
issn:
  • 10717544
  • 1071-7544
url: Link


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titleProlonged blood circulation of methotrexate by modulation of liposomal composition.
creatorHong, M S ; Lim, S J ; Lee, M K ; Kim, Y B ; Kim, C K
contributorHong, M S (correspondence author) ; Hong, M S (record owner)
ispartofDrug delivery, 2001 Oct-Dec, Vol.8(4), pp.231-237
identifierISSN: 1071-7544
subjectAnimals–Administration & Dosage ; Antineoplastic Agents–Blood ; Blood Circulation–Pharmacokinetics ; Cholesterol–Administration & Dosage ; Chromatography, High Pressure Liquid–Blood ; Drug Carriers–Pharmacokinetics ; Drug Stability–Pharmacokinetics ; Liposomes–Pharmacokinetics ; Methotrexate–Pharmacokinetics ; Particle Size–Pharmacokinetics ; Phosphatidylcholines–Pharmacokinetics ; Polyethylene Glycols–Pharmacokinetics ; Rats–Pharmacokinetics ; Rats, Sprague-Dawley–Pharmacokinetics ; Time Factors–Pharmacokinetics ; Tissue Distribution–Pharmacokinetics ; Antineoplastic Agents ; Drug Carriers ; Liposomes ; Phosphatidylcholines ; Polyethylene Glycols ; Cholesterol ; Methotrexate
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descriptionProlonged circulation by liposomal incorporation has been shown to enhance the therapeutic efficacy of drugs in many cases. The purpose of this study was to investigate whether the prolonged circulation of methotrexate (MTX) can be achieved by modulating the liposomal compositions. Various compositions of liposomes were prepared with 2:1 of phosphatidylcholine (PC) and cholesterol (CH) with or without distearoylphosphatidyl-ethanolamine-N-poly(ethyleneglycol) 2000 (DSPE-PEG). The MTX encapsulation efficiency depended on the type of PC used. It also appeared to increase by inclusion of DSPE-PEG. The size of liposomes decreased by the inclusion of DSPE-PEG. The inclusion of DSPE-PEG lowered the plasma-induced release of MTX from EggPC/CH and DPPC/CH liposomes, suggesting its enhancement effect on the liposomal stability. After intravenous injection to rats, the pharmaockinetics and biodistribution of MTX were significantly changed by liposomal incorporation and also by the composition of liposomes. The total body clearance of MTX incorporated in EggPC/CH, DPPC/CH, EggPC/CH/DSPE-PEG, and DPPC/CH/DSPE-PEG liposomes decreased 4.4-, 14.9-, 24.5-, and 53.1-fold, compared with that of free MTX. The ratio of MTX concentration in blood to liver and spleen after injection of DPPC/CH, EggPC/CH/DSPE-PEG, and DPPC/CH/DSPE-PEG liposomes was 5.4-, 8.5-, and 13.5-fold higher than that of EggPC/CH liposomes. Furthermore, the accumulation of MTX in the kidney, one of the organs in which MTX exhibits its toxicity, was significantly lowered by liposomal incorporation, especially by DSPE-PEG-containing liposomes. Taken together, DPPC/CH/DSPE-PEG liposomes most effectively prolonged the blood circulation, and reduced hepatosplenic and kidney uptake of MTX. DPPC/CH/DSPE-PEG liposomes may have potential as an efficient delivery system for MTX.
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titleProlonged blood circulation of methotrexate by modulation of liposomal composition.
authorHong, M S ; Lim, S J ; Lee, M K ; Kim, Y B ; Kim, C K
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