Preparation and Evaluation of Glutaraldehyde Cross-Linked Chitosan Microspheres as a Gadolinium Reservoir for Neutron-Capture Therapy.

Abstract

Chitosan microspheres (CMSs) containing water-soluble gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) were prepared by an emulsion method using Span 80 as a surfactant and glutaraldehyde (GA) as a cross-linker for the gadolinium neutron-capture therapy of cancer. When Gd-DTPA was applied at more than a 1:1 number ratio of its carboxylic groups to the amino groups of chitosan, the content of Gd in CMS was saturated at about 13% and the mass median diameter of CMS was increased beyond that of placebo CMS. The increase in the amount of Span 80 and GA applied led to a decrease in the CMS size and the Gd content. The electrostatic interaction between chitosan and Gd-DTPA and the preferential surface-hardening by GA contributed to the formation of fine, spherical, Gd-enriched and prolonged-releasing CMSs with a mass median diameter of 1.9 μm, a Gd content of 6.1% and a 50% dissolution time of 2.4 h.