Effect of pH variation on cross-linking of water-soluble and acid-soluble chitosan with sodium tripolyphosphate and gallium-67

Abstract

Background: Chitosan is a cationic biopolymer obtained from deacetylating chitin, a naturally compoundpresent in crustacean shell, fungi and exoskeleton of insects. Chitosan has various applications including drug and gene delivery systems, wound dressing and as scaffolds for tissue engineering, agriculture, textile, food and feed nanotechnology, waste water treatments. chitosan-TPP particle figure out as the most important and stable nanoparticle for chitosan application in various fields. Objective: At this study chitosan was chemically modified by sodium tripolyphosphate (TPP). Afterward, TPP-chitosan was radiolabeled with gallium-67 radionuclide. The effect of several factors on labeling yield such as chitosan solubility, acidity and concentration of TPP-chitosansolution, incubation time with gallium-67 were investigated. Methods: To prepare [67Ga] gallium-chitosan complex, chitosan (0.5 ml) was dissolved in 2.2 mCi of [67Ga] gallium chloride solution. The obtained solution was stirred for 5 min and then was kept for 30 min at room temperature. Radiochemical purity and radiolabeling yield was measured via radiochromatography that it was performed by using a radio thin-layer chromatography (TLC) scanner instrument. To investigate the effect of chitosan kind and concentration on the labeling yield, two kinds of chitosan (acid-soluble chitosan and water-soluble chitosan) with two different concentrations (1% and 0.5%) at different pH were used. In addition, labeling efficiency and stability of the 67Ga-TPP-chitosan complex (acidic/water soluble chitosan) at both concentrations (0.5 and 1%) at room temperature was assessed for 30, 45 and 60 min. Results: The incubation time has not significant effect on labeling yield. The acidic soluble chitosan, which has highest radiolabeling yield at pH=9.3-10.4, water soluble chitosan showed the highest radiolabeling yields at pH > 5. Also, the prepared complex was stable in the final solution at room temperature and can even be used 24 hours after preparation for further application. Conclusion: Taken together, the TPP modified water soluble chitosan at concentration 0.5 % depicted the highest radiochemical yield (>95 %) at the optimized condition (pH= 6.2–7.6). Therefore, TPP modified water soluble chitosan can be an effective carrier for therapeutic radionuclides for tumor treatment.