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Development of a nanocrystalline Paclitaxel formulation for HIPEC treatment

Lieselotte De Smet (UGent) , Pieter Colin (UGent) , Wim Ceelen (UGent) , Marc Bracke (UGent) , Jan Van Bocxlaer (UGent) , Jean Paul Remon (UGent) and Chris Vervaet (UGent)
(2012) PHARMACEUTICAL RESEARCH. 29(9). p.2398-2406
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Abstract
To develop a nanocrystalline paclitaxel formulation with a high paclitaxel-to-stabilizer ratio which can be used for hyperthermic intraperitoneal chemotherapy (HIPEC). Paclitaxel (PTX) nanocrystals were prepared via wet milling using Pluronic F127(A (R)) as stabilizer. The suitability of paclitaxel nanosuspensions for HIPEC treatment was evaluated by analyzing the cytotoxicity of both stabilizer and formulation, and by determining the maximum tolerated dose (MTD) and bioavailability. The effect on tumor growth was evaluated by magnetic resonance imaging (MRI) at day 7 and 14 after HIPEC treatment in rats with peritoneal carcinomatosis of ovarian origin. Monodisperse nanosuspensions (+/- 400 nm) were developed using Pluronic F127(A (R)) as single additive. The cytotoxicity and MTD of this nanocrystalline formulation was similar compared to Taxol(A (R)), while its bioavailability was higher. MRI data after HIPEC treatment with a PTX nanocrystalline suspension showed a significant reduction of tumor volume compared to the non-treated group. Although no significant differences on tumor volume were observed between Taxol(A (R)) and the nanosuspension, the rats treated with the nanosuspension recovered faster following the HIPEC procedure. Nanosuspensions with a high paclitaxel-to-stabilizer ratio are of interest for the treatment of peritoneal carcinomatosis of ovarian origin via HIPEC.
Keywords
ovarian cancer, paclitaxel, nanocrystal, hyperthermic intraperitoneal chemotherapy, wet milling, HYPERTHERMIC INTRAPERITONEAL CHEMOTHERAPY, PERITONEAL SURFACE MALIGNANCY, CYTOREDUCTIVE SURGERY, DRUG-DELIVERY, OVARIAN-CANCER, NANOPARTICLES, MANAGEMENT, RESISTANCE, MODEL

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Citation

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Chicago
De Smet, Lieselotte, Pieter Colin, Wim Ceelen, Marc Bracke, Jan Van Bocxlaer, Jean Paul Remon, and Chris Vervaet. 2012. “Development of a Nanocrystalline Paclitaxel Formulation for HIPEC Treatment.” Pharmaceutical Research 29 (9): 2398–2406.
APA
De Smet, Lieselotte, Colin, P., Ceelen, W., Bracke, M., Van Bocxlaer, J., Remon, J. P., & Vervaet, C. (2012). Development of a nanocrystalline Paclitaxel formulation for HIPEC treatment. PHARMACEUTICAL RESEARCH, 29(9), 2398–2406.
Vancouver
1.
De Smet L, Colin P, Ceelen W, Bracke M, Van Bocxlaer J, Remon JP, et al. Development of a nanocrystalline Paclitaxel formulation for HIPEC treatment. PHARMACEUTICAL RESEARCH. 2012;29(9):2398–406.
MLA
De Smet, Lieselotte et al. “Development of a Nanocrystalline Paclitaxel Formulation for HIPEC Treatment.” PHARMACEUTICAL RESEARCH 29.9 (2012): 2398–2406. Print.
@article{3007160,
  abstract     = {To develop a nanocrystalline paclitaxel formulation with a high paclitaxel-to-stabilizer ratio which can be used for hyperthermic intraperitoneal chemotherapy (HIPEC). 
Paclitaxel (PTX) nanocrystals were prepared via wet milling using Pluronic F127(A (R)) as stabilizer. The suitability of paclitaxel nanosuspensions for HIPEC treatment was evaluated by analyzing the cytotoxicity of both stabilizer and formulation, and by determining the maximum tolerated dose (MTD) and bioavailability. The effect on tumor growth was evaluated by magnetic resonance imaging (MRI) at day 7 and 14 after HIPEC treatment in rats with peritoneal carcinomatosis of ovarian origin. 
Monodisperse nanosuspensions (+/- 400 nm) were developed using Pluronic F127(A (R)) as single additive. The cytotoxicity and MTD of this nanocrystalline formulation was similar compared to Taxol(A (R)), while its bioavailability was higher. MRI data after HIPEC treatment with a PTX nanocrystalline suspension showed a significant reduction of tumor volume compared to the non-treated group. Although no significant differences on tumor volume were observed between Taxol(A (R)) and the nanosuspension, the rats treated with the nanosuspension recovered faster following the HIPEC procedure. 
Nanosuspensions with a high paclitaxel-to-stabilizer ratio are of interest for the treatment of peritoneal carcinomatosis of ovarian origin via HIPEC.},
  author       = {De Smet, Lieselotte and Colin, Pieter and Ceelen, Wim and Bracke, Marc and Van Bocxlaer, Jan and Remon, Jean Paul and Vervaet, Chris},
  issn         = {0724-8741},
  journal      = {PHARMACEUTICAL RESEARCH},
  keywords     = {ovarian cancer,paclitaxel,nanocrystal,hyperthermic intraperitoneal chemotherapy,wet milling,HYPERTHERMIC INTRAPERITONEAL CHEMOTHERAPY,PERITONEAL SURFACE MALIGNANCY,CYTOREDUCTIVE SURGERY,DRUG-DELIVERY,OVARIAN-CANCER,NANOPARTICLES,MANAGEMENT,RESISTANCE,MODEL},
  language     = {eng},
  number       = {9},
  pages        = {2398--2406},
  title        = {Development of a nanocrystalline Paclitaxel formulation for HIPEC treatment},
  url          = {http://dx.doi.org/10.1007/s11095-012-0765-x},
  volume       = {29},
  year         = {2012},
}

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