Preparation and in vitro evaluation of chitosan nanoparticles containing 5-[125Ⅰ] Iodo-2'deoxyuridine / 中华放射医学与防护杂志

ABSTRACT

Objective To prepare the chitosan nanoparticles loading 5-[125Ⅰ] Iodo-2'-deoxyuridine (125Ⅰ-UdR-CS-DLN) at 100-200 nm in diameter, and analyze the characteristic of drug sustained-releasing and tumor targeting. Methods Orthogonal experimental design and One-way analysis were applied to optimize the preparation of 125Ⅰ-UdR-CS-DLN using tripolyphosphate cross-linking. Dynamic dialysis was utilized to investigate the in vitro releasing characteristics of the nanoparticles. The tumor targeting effect of the nanoparticles was observed with laser confocal microscopy. Results The optimal conditions for preparing the nanoparticles at particle diameters (70. 39 ± 5.12 ) nm (PDI 0. 16 ± 0. 012 ) were 1 g/L of CS, 2 g/L of TPP, stirring rate 600 r/min, relative molecular mass of CS 3 × 103. The TEM results showed that the exterior of the nanoparticles was spheroid, with a uniform and fine dispersivity. The optimized condition with the initial 125Ⅰ-UdR concentration of 2. 96 MBq/ml at pH5 provided the highest loading capacity (1253. 55 MBq/g) and the highest entrapment rate (42. 35% ). The in vitro releasing curves of 125Ⅰ-UdR-CS-DLN followed Higuchi equation, shown a characteristic of long-acting preparation.Laser confocal microscopy observations approved that the tumor cells uptake of FITC-CS-nanoparticles were significantly more than that of normal cells. Conclusions Chitosan nanoparticles loading 125Ⅰ-UdR at diameters range 127. 81 ± 15. 25 nm (PDI 0. 240 ± 0. 035 ) were successfully prepared with the optimized conditions, and showed a characteristic of sustained-releasing and tumor targeting. The chitosan-based nanotechnology provided a new and efficient approach for the application of 125Ⅰ-UdR in intracellular radiotherapy for tumor.