Significant transport of doxorubicin into the brain with polysorbate 80- coated nanoparticles

Alexander E. Gulyaev, Svetlana E. Gelperina, Igor N. Skidan, Arkady S. Antropov, Gregory Ya Kivman, Jörg Kreuter

Research output: Contribution to journalArticle

444 Citations (Scopus)

Abstract

Purpose. To investigate the possibility of delivering of anticancer drugs into the brain using colloidal carriers (nanoparticles). Methods. Rats obtained 5 mg/kg of doxorubicin by i. v. injection in form of 4 preparations: 1. a simple solution in saline, 2. a simple solution in polysorbate 80 1% in saline, 3. bound to poly(butyl cyanoacrylate) nanoparticles, and 4. bound to poly(butyl cyanoacrylate) nanoparticles overcoated with 1% polysorbate 80 (Tween® 80). After sacrifice of the animals after 10 min, 1, 2, 4, 6, and 8 hours, the doxorubicin concentrations in plasma, liver, spleen, lungs, kidneys, heart and brain were determined after extraction by HPLC. Results. No significant difference in the body distribution was observed between the two solution formulations. The two nanoparticle formulations very significantly decreased the heart concentrations. High brain concentrations of doxorubicin (>6 μg/g) were achieved with the nanoparticles overcoated with polysorbate 80 between 2 and 4 hours. The brain concentrations observed with the other three preparations were always below the detection limit (<0.1 μg/g). Conclusions. The present study demonstrates that the brain concentration of systemically administered doxorubicin can be enhanced over 60-fold by binding to biodegradable poly(butyl cyanoacrylate) nanoparticles, overcoated with the nonionic surfactant polysorbate 80. It is highly probable that coated particles reached the brain intact and released the drug after endocytosis by the brain blood vessel endothelial cells.

Original languageEnglish
Pages (from-to)1564-1569
Number of pages6
JournalPharmaceutical Research
Volume16
Issue number10
DOIs
Publication statusPublished - 1999
Externally publishedYes

Fingerprint

Polysorbates
Nanoparticles
Doxorubicin
Brain
Cyanoacrylates
Endothelial cells
Nonionic surfactants
Blood vessels
Endocytosis
Sodium Chloride
Surface-Active Agents
Pharmaceutical Preparations
Liver
Blood Vessels
Limit of Detection
Rats
Animals
Spleen
Endothelial Cells
High Pressure Liquid Chromatography

Keywords

  • Brain targeting
  • Brain tumors
  • Doxorubicin
  • Nanoparticles
  • Polysorbate 80

ASJC Scopus subject areas

  • Chemistry(all)
  • Pharmaceutical Science
  • Pharmacology

Cite this

Significant transport of doxorubicin into the brain with polysorbate 80- coated nanoparticles. / Gulyaev, Alexander E.; Gelperina, Svetlana E.; Skidan, Igor N.; Antropov, Arkady S.; Kivman, Gregory Ya; Kreuter, Jörg.

In: Pharmaceutical Research, Vol. 16, No. 10, 1999, p. 1564-1569.

Research output: Contribution to journalArticle

Gulyaev, AE, Gelperina, SE, Skidan, IN, Antropov, AS, Kivman, GY & Kreuter, J 1999, 'Significant transport of doxorubicin into the brain with polysorbate 80- coated nanoparticles', Pharmaceutical Research, vol. 16, no. 10, pp. 1564-1569. https://doi.org/10.1023/A:1018983904537
Gulyaev, Alexander E. ; Gelperina, Svetlana E. ; Skidan, Igor N. ; Antropov, Arkady S. ; Kivman, Gregory Ya ; Kreuter, Jörg. / Significant transport of doxorubicin into the brain with polysorbate 80- coated nanoparticles. In: Pharmaceutical Research. 1999 ; Vol. 16, No. 10. pp. 1564-1569.
@article{df0374f4cee2435d847edde4e51439fa,
title = "Significant transport of doxorubicin into the brain with polysorbate 80- coated nanoparticles",
abstract = "Purpose. To investigate the possibility of delivering of anticancer drugs into the brain using colloidal carriers (nanoparticles). Methods. Rats obtained 5 mg/kg of doxorubicin by i. v. injection in form of 4 preparations: 1. a simple solution in saline, 2. a simple solution in polysorbate 80 1{\%} in saline, 3. bound to poly(butyl cyanoacrylate) nanoparticles, and 4. bound to poly(butyl cyanoacrylate) nanoparticles overcoated with 1{\%} polysorbate 80 (Tween{\circledR} 80). After sacrifice of the animals after 10 min, 1, 2, 4, 6, and 8 hours, the doxorubicin concentrations in plasma, liver, spleen, lungs, kidneys, heart and brain were determined after extraction by HPLC. Results. No significant difference in the body distribution was observed between the two solution formulations. The two nanoparticle formulations very significantly decreased the heart concentrations. High brain concentrations of doxorubicin (>6 μg/g) were achieved with the nanoparticles overcoated with polysorbate 80 between 2 and 4 hours. The brain concentrations observed with the other three preparations were always below the detection limit (<0.1 μg/g). Conclusions. The present study demonstrates that the brain concentration of systemically administered doxorubicin can be enhanced over 60-fold by binding to biodegradable poly(butyl cyanoacrylate) nanoparticles, overcoated with the nonionic surfactant polysorbate 80. It is highly probable that coated particles reached the brain intact and released the drug after endocytosis by the brain blood vessel endothelial cells.",
keywords = "Brain targeting, Brain tumors, Doxorubicin, Nanoparticles, Polysorbate 80",
author = "Gulyaev, {Alexander E.} and Gelperina, {Svetlana E.} and Skidan, {Igor N.} and Antropov, {Arkady S.} and Kivman, {Gregory Ya} and J{\"o}rg Kreuter",
year = "1999",
doi = "10.1023/A:1018983904537",
language = "English",
volume = "16",
pages = "1564--1569",
journal = "Pharmaceutical Research",
issn = "0724-8741",
publisher = "Springer New York",
number = "10",

}

TY - JOUR

T1 - Significant transport of doxorubicin into the brain with polysorbate 80- coated nanoparticles

AU - Gulyaev, Alexander E.

AU - Gelperina, Svetlana E.

AU - Skidan, Igor N.

AU - Antropov, Arkady S.

AU - Kivman, Gregory Ya

AU - Kreuter, Jörg

PY - 1999

Y1 - 1999

N2 - Purpose. To investigate the possibility of delivering of anticancer drugs into the brain using colloidal carriers (nanoparticles). Methods. Rats obtained 5 mg/kg of doxorubicin by i. v. injection in form of 4 preparations: 1. a simple solution in saline, 2. a simple solution in polysorbate 80 1% in saline, 3. bound to poly(butyl cyanoacrylate) nanoparticles, and 4. bound to poly(butyl cyanoacrylate) nanoparticles overcoated with 1% polysorbate 80 (Tween® 80). After sacrifice of the animals after 10 min, 1, 2, 4, 6, and 8 hours, the doxorubicin concentrations in plasma, liver, spleen, lungs, kidneys, heart and brain were determined after extraction by HPLC. Results. No significant difference in the body distribution was observed between the two solution formulations. The two nanoparticle formulations very significantly decreased the heart concentrations. High brain concentrations of doxorubicin (>6 μg/g) were achieved with the nanoparticles overcoated with polysorbate 80 between 2 and 4 hours. The brain concentrations observed with the other three preparations were always below the detection limit (<0.1 μg/g). Conclusions. The present study demonstrates that the brain concentration of systemically administered doxorubicin can be enhanced over 60-fold by binding to biodegradable poly(butyl cyanoacrylate) nanoparticles, overcoated with the nonionic surfactant polysorbate 80. It is highly probable that coated particles reached the brain intact and released the drug after endocytosis by the brain blood vessel endothelial cells.

AB - Purpose. To investigate the possibility of delivering of anticancer drugs into the brain using colloidal carriers (nanoparticles). Methods. Rats obtained 5 mg/kg of doxorubicin by i. v. injection in form of 4 preparations: 1. a simple solution in saline, 2. a simple solution in polysorbate 80 1% in saline, 3. bound to poly(butyl cyanoacrylate) nanoparticles, and 4. bound to poly(butyl cyanoacrylate) nanoparticles overcoated with 1% polysorbate 80 (Tween® 80). After sacrifice of the animals after 10 min, 1, 2, 4, 6, and 8 hours, the doxorubicin concentrations in plasma, liver, spleen, lungs, kidneys, heart and brain were determined after extraction by HPLC. Results. No significant difference in the body distribution was observed between the two solution formulations. The two nanoparticle formulations very significantly decreased the heart concentrations. High brain concentrations of doxorubicin (>6 μg/g) were achieved with the nanoparticles overcoated with polysorbate 80 between 2 and 4 hours. The brain concentrations observed with the other three preparations were always below the detection limit (<0.1 μg/g). Conclusions. The present study demonstrates that the brain concentration of systemically administered doxorubicin can be enhanced over 60-fold by binding to biodegradable poly(butyl cyanoacrylate) nanoparticles, overcoated with the nonionic surfactant polysorbate 80. It is highly probable that coated particles reached the brain intact and released the drug after endocytosis by the brain blood vessel endothelial cells.

KW - Brain targeting

KW - Brain tumors

KW - Doxorubicin

KW - Nanoparticles

KW - Polysorbate 80

UR - http://www.scopus.com/inward/record.url?scp=0032712180&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032712180&partnerID=8YFLogxK

U2 - 10.1023/A:1018983904537

DO - 10.1023/A:1018983904537

M3 - Article

C2 - 10554098

AN - SCOPUS:0032712180

VL - 16

SP - 1564

EP - 1569

JO - Pharmaceutical Research

JF - Pharmaceutical Research

SN - 0724-8741

IS - 10

ER -