Development of biodegradable, biocompatible microparticles for controlled cisplatin release

• Published in: The Thoracic and Cardiovascular Surgeon
• Main Authors: Lescan, M, Walker, T, Wendel, HP, Steger, V, Schlensak, C
• Format: Conference Proceeding
• Language: English
• Published: 23.01.2013
• ISSN: 0171-6425; 1439-1902
• DOI: 10.1055/s-0032-1332512

Objectives: After resection of the mesothelioma-affected tissue, cisplatin is used locally to eliminate residual tumor cells. Despite this treatment, the recurrence rate is relatively high. Therefore, the thoracic cavity might be treated with biodegradable, biocompatible microparticles loaded with cisplatin and fixed in the thorax instead of a single cisplatin irrigation. However, the effective loading of the microparticles with a sufficient concentration of cisplatin still remains a challenge. Methods: The production method is based on the formation of a multiple Water-1/Oil/Water-2-emulsion followed by solvent extraction/evaporation. The resulting microparticles contain a portion of the drug, brought in by the inner phase (Water-1). The concentration of the drug in the inner phase could be increased from 1 mg/ml to 1.5 mg/ml by using a cisplatin powder instead of a NaCl (0.9%)-Cisplatin (1 mg/ml) solution. Furthermore, an additional saturation of the outer continuous phase (Water-2) with 1 mg/ml Cisplatin resulted in a further increase of the encapsulation efficiency from 1% to 3% – 26%. The drug loading was between 0.3 mg and 1.2 mg per g microparticles. Results: The modification of the loading methods led to a 30 times higher encapsulation efficiency and a higher cisplatin concentration in the microparticles. An in vitro pharmacokinetic study showed that nearly 90% of the drug was released after 30 days into the medium (Figure 1). Conclusion: Biodegradable, biocompatible microparticles loaded with cisplatin and employed postoperatively in the thoracic cavity would allow a controlled release of cisplatin over several weeks to reduce the recurrence rate of pleural mesothelioma. Fig. 1: Cumulative cisplatin release from microparticles over 30 days