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 language | English |
|---|---|
| Pages (from-to) | 1564-1569 |
| Number of pages | 6 |
| Journal | Pharmaceutical Research |
| Volume | 16 |
| Issue number | 10 |
| DOIs | |
| Publication status | Published - 1999 |
| Externally published | Yes |
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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 journal › Article
}
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 -