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Properties and effects of a novel liquid crystal nanoparticle formulation of docetaxel in a prostate cancer mouse model.

Cervin, Camilla; Tinzl, Martina LU ; Johnsson, Markus; Abrahamsson, Per-Anders LU ; Tiberg, Fredrik and Dizeyi, Nishtman LU (2010) In European Journal of Pharmaceutical Sciences 41. p.369-375
Abstract
Treatment with docetaxel is the standard of care as first line chemotherapy in castration resistant prostate cancer. Due to serious side effects from the commercially available Taxotere formulation, we aimed to develop a safe and effective nanoparticle formulation of docetaxel. Liquid crystal nanoparticles (LCNPs), based on phosphatidyl choline, glycerol dioleate and polysorbate 80 dispersed in excess aqueous solution, were produced by simple procedures as carriers of docetaxel. Their effect on tumor growth in male SCID mice inoculated with PC-3 cells was compared to the effect of Taxotere and empty LCNP vehicle. Immunohistochemistry was performed to evaluate cell proliferation, angiogenesis and apoptosis in tumor tissue. Docetaxel and... (More)
Treatment with docetaxel is the standard of care as first line chemotherapy in castration resistant prostate cancer. Due to serious side effects from the commercially available Taxotere formulation, we aimed to develop a safe and effective nanoparticle formulation of docetaxel. Liquid crystal nanoparticles (LCNPs), based on phosphatidyl choline, glycerol dioleate and polysorbate 80 dispersed in excess aqueous solution, were produced by simple procedures as carriers of docetaxel. Their effect on tumor growth in male SCID mice inoculated with PC-3 cells was compared to the effect of Taxotere and empty LCNP vehicle. Immunohistochemistry was performed to evaluate cell proliferation, angiogenesis and apoptosis in tumor tissue. Docetaxel and lipid excipients were dispersed into well-defined LCNP, stable during long-term storage. Mice subjected to LCNP/docetaxel formulation showed a better tumor regression than mice treated with Taxotere, with an indication of better tolerability. Immunohistochemical staining showed a decreased expression of Ki-67 in tumors from LCNP/docetaxel treated animals, especially in the cores of the tumors, suggesting better penetration/absorption compared to Taxotere. A new lipid-based nanoparticle formulation has been developed as carrier for docetaxel. Treatment effects in SCID mice indicate that this may be an interesting alternative to the current marketed formulation product. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
European Journal of Pharmaceutical Sciences
volume
41
pages
369 - 375
publisher
Elsevier
external identifiers
  • wos:000281995200021
  • pmid:20633647
  • scopus:77955846700
ISSN
1879-0720
DOI
10.1016/j.ejps.2010.07.003
language
English
LU publication?
yes
id
deb2d8e9-a4d8-44bb-8c28-8aa910a8dcf3 (old id 1644919)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/20633647?dopt=Abstract
date added to LUP
2010-08-03 09:42:17
date last changed
2018-06-17 04:57:38
@article{deb2d8e9-a4d8-44bb-8c28-8aa910a8dcf3,
  abstract     = {Treatment with docetaxel is the standard of care as first line chemotherapy in castration resistant prostate cancer. Due to serious side effects from the commercially available Taxotere formulation, we aimed to develop a safe and effective nanoparticle formulation of docetaxel. Liquid crystal nanoparticles (LCNPs), based on phosphatidyl choline, glycerol dioleate and polysorbate 80 dispersed in excess aqueous solution, were produced by simple procedures as carriers of docetaxel. Their effect on tumor growth in male SCID mice inoculated with PC-3 cells was compared to the effect of Taxotere and empty LCNP vehicle. Immunohistochemistry was performed to evaluate cell proliferation, angiogenesis and apoptosis in tumor tissue. Docetaxel and lipid excipients were dispersed into well-defined LCNP, stable during long-term storage. Mice subjected to LCNP/docetaxel formulation showed a better tumor regression than mice treated with Taxotere, with an indication of better tolerability. Immunohistochemical staining showed a decreased expression of Ki-67 in tumors from LCNP/docetaxel treated animals, especially in the cores of the tumors, suggesting better penetration/absorption compared to Taxotere. A new lipid-based nanoparticle formulation has been developed as carrier for docetaxel. Treatment effects in SCID mice indicate that this may be an interesting alternative to the current marketed formulation product.},
  author       = {Cervin, Camilla and Tinzl, Martina and Johnsson, Markus and Abrahamsson, Per-Anders and Tiberg, Fredrik and Dizeyi, Nishtman},
  issn         = {1879-0720},
  language     = {eng},
  pages        = {369--375},
  publisher    = {Elsevier},
  series       = {European Journal of Pharmaceutical Sciences},
  title        = {Properties and effects of a novel liquid crystal nanoparticle formulation of docetaxel in a prostate cancer mouse model.},
  url          = {http://dx.doi.org/10.1016/j.ejps.2010.07.003},
  volume       = {41},
  year         = {2010},
}