Encapsulation of Zn-DTPA into poly lactic-co-glycolic acid nanoparticles via a modified double emulsion method for extended release into lung fluid

Diethylenetriaminepentaacetate (DTPA) is an approved chemical agent for decorporation of internalized actinides. During a radiological or nuclear incident, inhalation of radioactive material into the lungs is one of the main paths of hazardous exposure. High affinity of DTPA toward actinides makes it a suitable actinide decorporation agent that accelerates their excretion from the human body. Polymeric nanoparticles are ideal for use in prolonging drug release, as they are biocompatible, non-toxic, and have been approved for therapeutic use by the Federal Drug Administration. Poly lactic-co-glycolic acid (PLGA) was chosen for this research as previous literature has shown that PLGA NPs would delay the drug release of other therapeutic agents. PLGA NPs encapsulating Zn-DTPA were synthesized for the first time to extend the DTPA release in human lungs. Since the physicochemical properties of a particle such as its size and functional groups can influence its uptake by lung cells and tissues in vivo, the synthesized PLGA NPs encapsulating ZnDTPA were characterized by transmission electron microscopy, Fourier-transform infrared spectroscopy, and dynamic light scattering. The loading capacity of Zn-DTPA in the PLGA NPs achieved in this formulation was determined to be 10(±1)% (w/w) through use of Liquid Chromatography-Mass Spectrometry (LC-MS). Extended release of Zn-DTPA from the PLGA NPs into simulated lung fluid was confirmed via dialysis experiments using continuous Ultraviolet (UV) absorbance monitoring. LC-MS was also used to demonstrate the extended release of DTPA from these PLGA NPs; a significantly longer half-time was achieved compared to that obtained for Zn-DTPA itself. As the dialysis lung fluid volume increased, longer half-times were observed for both Zn-DTPA and Zn-DTPA encapsulated by PLGA NPs. Furthermore, as expected, decreasing the concentration of Zn-DTPA in dialysis experiments increased the half-time. The purpose of this study was to extend the drug release through an optimized formulation of DTPA encapsulated PLGA NPs as compared to the free DTPA treatment in vitro study.