Preclinical evaluation of local prolonged release of paclitaxel from gelatin microspheres for the prevention of recurrence of peritoneal carcinomatosis in advanced ovarian cancer
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 microsp...
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Published in | Scientific reports Vol. 9; no. 1; pp. 14881 - 19 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
London
Nature Publishing Group UK
16.10.2019
Nature Publishing Group |
Subjects | |
Online Access | Get full text |
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Summary: | 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 µg PTX/mg MS) was obtained by immersion of GP-MS in aqueous PTX nanosuspension (PTX
nano
-GP-MS) instead of ethanolic PTX solution (PTX
EtOH
-GP-MS). PTX release from PTX-GP-MS was prolonged. PTX
nano
-GP-MS displayed a more controlled release compared to a biphasic release from PTX
EtOH
-GP-MS. Anticancer efficacy of IP PTX-GP-MS (PTX
EtOH
-GP-MS, D = 7.5 mg PTX/kg; PTX
nano
-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. PTX
nano
-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 PTX
nano
-GP-MS caused drug-related toxicity in 27% of high-dosed PTX
nano
-GP-MS-treated mice. Dose simulations for PTX
nano
-GP-MS demonstrated an optimal survival without drug-induced toxicity in a range of 7.5–15 mg PTX/kg. Low-dosed PTX
nano
-GP-MS can be a promising IP drug delivery system to prevent recurrent ovarian cancer. |
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ISSN: | 2045-2322 2045-2322 |
DOI: | 10.1038/s41598-019-51419-y |