Inhalable Chitosan Tripolyphosphate Nanoparticles for Extended Release of DTPA into Lung Fluid

Diethylenetriaminepentaacetic acid (DTPA) is a non-toxic chemical agent with strong actinide chelation properties that has been approved for decorporation of internalized radioactive nuclides such as plutonium and americium. However, DTPA exhibits poor inhalation delivery efficacy for emergency treatment due to short retention in the lungs. Chitosan (CS) is a biodegradable, biocompatible and hydrophilic polymer that adheres to biological mucosa. CS nanoparticles encapsulating DTPA were prepared by the ionic gelation method using sodium tripolyphosphate (TPP). The CSDTPA/TPP nanoparticles have been characterized for reversible unfolding in a simulated lung fluid. Extended release of the agent, for improved efficacy of actinide decorporation, was monitored by liquid chromatography-mass spectrometry. The in vitro release profile exhibits an initial burst, followed by a sustained release to reach finally a stable level. More importantly lysozyme, a protein in respiratory tract secretions, exhibits no negative impact on the extended release of DTPA from the CS-DTPA/TPP nanoparticles.