Abstract
Introduction: Improved drug delivery mechanisms for the treatment of residual peritoneal cancer cells following cytoreduction surgery are needed. Alginate microcapsules are a potentially useful mechanism for delivery of bioengineered cells, but when injected into the peritoneum, their distribution and properties are not well described. Methods: Aliquots of 300, 600 or 1200 microcapsules were injected into the peritoneum of 81 mice. Mice were sacrificed at 6, 12, 18, and 48 days and laparotomy was performed to quantify the distribution of microspheres. Results: The injections were well tolerated for up to 48 days. No peritoneal adherence or inflammatory reaction was noted to the microcapsules. Injection of 1200 microcapsules resulted in a better overall persistence and widespread peritoneal distribution at up to 48 days. The volume of fluid used for injection of the microcapsules did not affect their distribution or persistence. Conclusion: The intraperitoneal injection of alginate microspheres allows wide and persistent distribution throughout the abdominal cavity. The next step is to test the distribution of microcapsules when delivered following surgery in a rodent model.
Highlights
Improved drug delivery mechanisms for the treatment of residual peritoneal cancer cells following cytoreduction surgery are needed
This study addresses the first step in the development of an alginate-microcapsule technology for delivering thymidine phosphorylase (TP)-producing cells to the peritoneum
Alginate microcapsules were present in the peritoneal cavity of 66 of the 81 sacrificed mice (81%)
Summary
Improved drug delivery mechanisms for the treatment of residual peritoneal cancer cells following cytoreduction surgery are needed. Injection of 1200 microcapsules resulted in a better overall persistence and widespread peritoneal distribution at up to 48 days. Cytoreduction surgery and heated intraperitoneal chemotherapy (CRS + HIPEC), combined with systemic chemotherapy for residual microscopic disease, are currently used to treat patients with peritoneal carcinomatosis from colorectal cancer (CRC). This therapeutic approach has a 20% - 30% 5-year overall survival, and has a 30% - 35% major morbidity rate and 0% - 4% perioperative mortality when conducted at experienced centres [1,2,3,4]. Prolonged intravenous 5-FU therapy is cumbersome for the postoperative patient
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