Ionic strength-sensitive pullulan acetate nanoparticles (PAN) for intratumoral administration of radioisotope: Ionic strength-dependent aggregation behavior and ^99mTechnetium retention property

In order to design an effective intratumoral radioisotope carrier, a self-assembled nanoparticle evidencing ionic strength (IS)-sensitivity from a polysaccharide derivative (pullulan acetate nanoparticle (PAN)) was prepared via dialysis. The PAN had a spherical shape in a range of size of 50-130 nm and a low critical aggregation concentration (CAC) (<8 μg/mL). With increases in the IS of the dialysis media (IS_dia), the CAC of PAN was reduced gradually and the rigidity of the hydrophobic core in PAN was increased. This suggests that the property of PAN was altered more hydrophobically at high IS values. The stabilities of PANs prepared from various IS_dia were also monitored with changes in the turbidity and particle size in different IS solutions. In the case of PAN prepared at an IS_dia = 0.0, the turbidity was dramatically reduced with increasing IS due to the facilitation of aggregation between the particles, whereas in the other cases, these changes were negligible. This finding indicates that PAN prepared in distilled water (IS = 0.0) can be readily injected as the consequence of its nano-size, and accumulates quickly, then remains in the tumor site for a considerable period (IS = 0.15). In order to closely estimate the potential of PAN as a radioisotope carrier, the radioisotope labeling efficiency of PAN with no chelating agents was evaluated. PAN evidenced a high degree of ^99mTechnetium (^99mTc) labeling efficiency (approximately 98%). The percentage retention rate (%RR) of the ^99mTc-labeled PAN was significantly longer than that of the free ^99mTc (p < 0.05), due largely to PAN's IS-sensitivity. In conclusion, PAN may constitute a new approach to the achievement of maximal radioisotope efficiency with regard to intratumoral administration.