CISPLATIN RELEASE CHARACTERISTICS FROM AMORPHOUS CALCIUM POLYPHOSPHATE MATRICES FOR THE ADJUNCTIVE TREATMENT OF ORAL SQUAMOUS CELL CARCINOMA

Abstract

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.