Improving Decorporation Efficacy of DTPA and HOPO Using Chitosan/TPP Nanoparticles: Preparation, Characterization and Release Testing

Abstract

Chitosan (CS) is a non-toxic, biodegradable and biocompatible polymer. It is hydrophilic and has adhesion to biological mucosa. Its amino groups can link with the chelating agents that have been identified for decorporating internalized radionuclides such as plutonium and americium. These chelating agents include diethylene triaminepentaacetic acid (DTPA) and 1,5,10,14-tetra(1-hydroxy-2-pyridon-6-oyl)-1,5,10,14-tetraazatetradecane (3,4,3-LI(1,2-HOPO)). The purpose of this research is to synthesize chitosan nanoparticles with encapsulated DTPA or 3,4,3-LI(1,2-HOPO), in a hope to improve the efficacy of the decorporation agents by taking advantage of the mucoadhesion property of chitosan. Chitosan nanoparticles encapsulated with decorporation agents (DTPA and HOPO) were synthesized by ionic gelation method, in the presence of a cross-linker sodium tripolyphosphate (TPP). Reversibility of ionic gelation makes it feasible to unfold the chitosan nanoparticles and release the encapsulated DTPA or HOPO. The resultant CS-DTPA/TPP and CS-HOPO/TPP nanoparticles were characterized by transmission electron microscopy, Fourier transform infrared spectroscopy and dynamic light scattering, which can provide information about morphology, chemical structure and size distribution, respectively. The CS/TPP, CS-DTPA/TPP and CS-HOPO/TPP nanoparticles show a mono-morphology which is full and dense spherical structure. CS-DTPA/TPP and CS-HOPO/TPP nanoparticles have a similar iii size distribution, which indicates that the majority of the particles are smaller than 100nm. The release profiles of CS-DTPA/TPP and CS-HOPO/TPP nanoparticles were obtained via in vitro release studies. The release process includes an initial burst period, a slow release in the later stage, and a relatively stable level in the final stage. Within the initial burst period, the cumulative amounts of DTPA and HOPO account for 70-80% and 60-70% of the final cumulative amounts, respectively. Lysozyme has no effect on the drug release from the CS-DTPA/TPP and CS-HOPO/TPP nanoparticles, no matter what weight ratio of the decorporation agent (DTPA or HOPO) to chitosan is. Lysozyme, existing in respiratory tract secretions, cannot influence the 3-stage release process. This cationic protein will not greatly change the final cumulative amount of the decorporation agents released from the CS-DTPA/TPP or CS-HOPO/TPP nanoparticles.