Cisplatin is an effective chemotheraputic agent for head and neck squamous cell
carcinoma particularly in conjunction with radiation therapy. Unfortunately, its cytotoxic
profile and associated systemic side effects limit its clinical efficacy. A localized
delivery system was developed for cisplatin by processing calcium polyphosphate (CPP)
in a multistep gelling protocol, with the goal of limiting its systemic toxicity and
enhancing its overall clinical applicability. In addition, a novel method for processing the
material was examined utilizing cold isostatic pressure (CIP) to allow for miniaturization
of the system into an implantable device. The integration of cisplatin into the matrix was
examined for efficient and dose dependent loading via dissolution of the final product
and measurement of platinum concentrations by inductively coupled plasma optical
emission spectrometry (ICP-OES). Drug release was measured in vitro by placing the
CPP-cisplatin matrix into TRIS buffer solution while measuring the platinum
concentration at given intervals from 0.5 hours to 14 days. The cytotoxicity of the
cisplatin against L1210 cells was examined using an MTT assay following a 12-hour
elution. The material demonstrated a predictable and dose dependent loading of cisplatin,
although the release of the drug showed variability exemplified by a more pronounced
burst release with aging of the stock CPP glass particulate. The CPP/cisplatin matrix
exhibited cytotoxic effects after processing. This work suggests that further evaluation of
this material as a matrix for cisplatin delivery should be undertaken in an attempt to
normalize release, maximize the concentration within the system and further optimize the
bead format in order to improve the potential for clinical usage.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:NSHD.ca#10222/48585 |
| Date | 07 March 2014 |
| Creators | Shaffner, Matthew |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
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