Enhanced Exposure of a Chemotherapeutic Drug to the Lymphatic System with the use of PEGModified and Nano-Sized Drug Carriers

Gemma M. Ryan1, Lisa M. Kaminskas1, Michelle P. McIntosh1, Brian D. Kelly2, David J. Owen2 and Christopher J.H. Porter1

1Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, Victoria, 3052, Australia; 2Starpharma Pty. Ltd, Melbourne, Victoria, 3004, Australia

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Summary
The lymphatic system is a major pathway by which metastasizing cancers spread throughout the body. Metastasizing cancers that arrest within lymph nodes are also able to seed further tumours to distal locations. Targeting chemotherapeutic agents towards the lymphatic system offers an approach to improve the treatment of lymph-metastatic cancers and to potentially limit systemic side effects commonly associated with chemotherapy. The current study therefore assessed the ability of different nano-sized, polyethylene glycol (PEG) modified drug carriers to enhance the exposure of the anti-cancer drug doxorubicin to the lymphatic system in rats after intravenous or subcutaneous administration. A dendrimer-based formulation of doxorubicin significantly improved the lymphatic access of the drug when compared to the administration of a solution formulation and a liposomal formulation of doxorubicin. The work demonstrates the potential for dendrimerbased drug delivery systems to improve the exposure of lymph-resident metastases to chemotherapeutic drugs.

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