Properties and effects of a novel liquid crystal nanoparticle formulation of docetaxel in a prostate cancer mouse model.
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.
Cervin
Camilla
C
Camurus, Ideon Science Park, Sölvegatan 41, Lund, Sweden. camilla.cervin@camurus.com
Tinzl
Martina
M
Johnsson
Markus
M
Abrahamsson
Per-Anders
PA
Tiberg
Fredrik
F
Dizeyi
Nishtman
N
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000627:therapeutic use*; D000077143:Docetaxel; D006801:Humans; D008297:Male; D051379:Mice; D016513:Mice, SCID; D053758:Nanoparticles; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D043823:Taxoids / Q000008:administration & dosage / Q000627:therapeutic use*; D014183:Transplantation, Heterologous
D000972:Antineoplastic Agents, Phytogenic; D043823:Taxoids; D000077143:Docetaxel