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Preclinical evaluation of local prolonged release of paclitaxel from gelatin microspheres for the prevention of recurrence of peritoneal carcinomatosis in advanced ovarian cancer

Kaat De Clercq (UGent) , Feifan Xie (UGent) , Olivier De Wever (UGent) , Benedicte Descamps (UGent) , Anne Hoorens (UGent) , An Vermeulen, Wim Ceelen (UGent) and Chris Vervaet (UGent)
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Abstract
Patients with advanced ovarian cancer develop recurrence despite initial treatment response to standard treatment of surgery and intravenous/intraperitoneal (IP) chemotherapy, partly due to a limited peritoneal exposure time of chemotherapeutics. Paclitaxel-loaded genipin-crosslinked gelatin microspheres (PTX-GP-MS) are evaluated for the treatment of microscopic peritoneal carcinomatosis and prevention of recurrent disease. The highest drug load (39.2 mu g PTX/mg MS) was obtained by immersion of GP-MS in aqueous PTX nanosuspension (PTXnano-GP-MS) instead of ethanolic PTX solution (PTXEtOH-GP-MS). PTX release from PTX-GP-MS was prolonged. PTXnano-GP-MS displayed a more controlled release compared to a biphasic release from PTX-GP-MS. Anticancer efficacy of IP PTX-GP-MS (PTXEtOH-GP-MS, D = 7.5 mg PTX/kg; PTXnano-GP-MS D= 7.5 and 35 mg PTX/kg), IP nanoparticular albumin-bound PTX (D = 35 mg PTX/kg) and controls (0.9% NaCl, blank GP-MS) was evaluated in a microscopic peritoneal carcinomatosis xenograft mouse model. PTXnano-GP-MS showed superior anticancer efficacy with significant increased survival time, decreased peritoneal carcinomatosis index score and ascites incidence. However, prolonged PTX release over 14 days from PTXnano-GP-MS caused drug-related toxicity in 27% of high-dosed PTXnano-GP-MS-treated mice. Dose simulations for PTXnano-GP-MS demonstrated an optimal survival without drug-induced toxicity in a range of 7.5-15 mg PTX/kg. Low-dosed PTXnano-GP-MS can be a promising IP drug delivery system to prevent recurrent ovarian cancer.
Keywords
HYPERTHERMIC INTRAPERITONEAL CHEMOTHERAPY, CASPASE-CLEAVED CYTOKERATIN-18, DRUG-DELIVERY SYSTEMS, THERMOSENSITIVE HYDROGEL, CYTOREDUCTIVE SURGERY, IN-VITRO, SERUM BIOMARKER, TUMOR HYPOXIA, PHASE-II, CISPLATIN

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MLA
De Clercq, Kaat, et al. “Preclinical Evaluation of Local Prolonged Release of Paclitaxel from Gelatin Microspheres for the Prevention of Recurrence of Peritoneal Carcinomatosis in Advanced Ovarian Cancer.” SCIENTIFIC REPORTS, vol. 9, 2019.
APA
De Clercq, K., Xie, F., De Wever, O., Descamps, B., Hoorens, A., Vermeulen, A., … Vervaet, C. (2019). Preclinical evaluation of local prolonged release of paclitaxel from gelatin microspheres for the prevention of recurrence of peritoneal carcinomatosis in advanced ovarian cancer. SCIENTIFIC REPORTS, 9.
Chicago author-date
De Clercq, Kaat, Feifan Xie, Olivier De Wever, Benedicte Descamps, Anne Hoorens, An Vermeulen, Wim Ceelen, and Chris Vervaet. 2019. “Preclinical Evaluation of Local Prolonged Release of Paclitaxel from Gelatin Microspheres for the Prevention of Recurrence of Peritoneal Carcinomatosis in Advanced Ovarian Cancer.” SCIENTIFIC REPORTS 9.
Chicago author-date (all authors)
De Clercq, Kaat, Feifan Xie, Olivier De Wever, Benedicte Descamps, Anne Hoorens, An Vermeulen, Wim Ceelen, and Chris Vervaet. 2019. “Preclinical Evaluation of Local Prolonged Release of Paclitaxel from Gelatin Microspheres for the Prevention of Recurrence of Peritoneal Carcinomatosis in Advanced Ovarian Cancer.” SCIENTIFIC REPORTS 9.
Vancouver
1.
De Clercq K, Xie F, De Wever O, Descamps B, Hoorens A, Vermeulen A, et al. Preclinical evaluation of local prolonged release of paclitaxel from gelatin microspheres for the prevention of recurrence of peritoneal carcinomatosis in advanced ovarian cancer. SCIENTIFIC REPORTS. 2019;9.
IEEE
[1]
K. De Clercq et al., “Preclinical evaluation of local prolonged release of paclitaxel from gelatin microspheres for the prevention of recurrence of peritoneal carcinomatosis in advanced ovarian cancer,” SCIENTIFIC REPORTS, vol. 9, 2019.
@article{8632941,
  abstract     = {Patients with advanced ovarian cancer develop recurrence despite initial treatment response to standard treatment of surgery and intravenous/intraperitoneal (IP) chemotherapy, partly due to a limited peritoneal exposure time of chemotherapeutics. Paclitaxel-loaded genipin-crosslinked gelatin microspheres (PTX-GP-MS) are evaluated for the treatment of microscopic peritoneal carcinomatosis and prevention of recurrent disease. The highest drug load (39.2 mu g PTX/mg MS) was obtained by immersion of GP-MS in aqueous PTX nanosuspension (PTXnano-GP-MS) instead of ethanolic PTX solution (PTXEtOH-GP-MS). PTX release from PTX-GP-MS was prolonged. PTXnano-GP-MS displayed a more controlled release compared to a biphasic release from PTX-GP-MS. Anticancer efficacy of IP PTX-GP-MS (PTXEtOH-GP-MS, D = 7.5 mg PTX/kg; PTXnano-GP-MS D= 7.5 and 35 mg PTX/kg), IP nanoparticular albumin-bound PTX (D = 35 mg PTX/kg) and controls (0.9% NaCl, blank GP-MS) was evaluated in a microscopic peritoneal carcinomatosis xenograft mouse model. PTXnano-GP-MS showed superior anticancer efficacy with significant increased survival time, decreased peritoneal carcinomatosis index score and ascites incidence. However, prolonged PTX release over 14 days from PTXnano-GP-MS caused drug-related toxicity in 27% of high-dosed PTXnano-GP-MS-treated mice. Dose simulations for PTXnano-GP-MS demonstrated an optimal survival without drug-induced toxicity in a range of 7.5-15 mg PTX/kg. Low-dosed PTXnano-GP-MS can be a promising IP drug delivery system to prevent recurrent ovarian cancer.},
  articleno    = {14881},
  author       = {De Clercq, Kaat and Xie, Feifan and De Wever, Olivier and Descamps, Benedicte and Hoorens, Anne and Vermeulen, An and Ceelen, Wim and Vervaet, Chris},
  issn         = {2045-2322},
  journal      = {SCIENTIFIC REPORTS},
  keywords     = {HYPERTHERMIC INTRAPERITONEAL CHEMOTHERAPY,CASPASE-CLEAVED CYTOKERATIN-18,DRUG-DELIVERY SYSTEMS,THERMOSENSITIVE HYDROGEL,CYTOREDUCTIVE SURGERY,IN-VITRO,SERUM BIOMARKER,TUMOR HYPOXIA,PHASE-II,CISPLATIN},
  language     = {eng},
  pages        = {19},
  title        = {Preclinical evaluation of local prolonged release of paclitaxel from gelatin microspheres for the prevention of recurrence of peritoneal carcinomatosis in advanced ovarian cancer},
  url          = {http://dx.doi.org/10.1038/s41598-019-51419-y},
  volume       = {9},
  year         = {2019},
}

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