Biodegradable micro-sized discoidal polymeric particles for lung-targeted delivery system

Abstract

Various types of particle-based drug delivery systems have been explored for the treatment of pulmonary diseases; however, bio-distribution and elimination of the particles should be monitored for better understanding of their therapeutic efficacy and safety. This study aimed to characterize the biological properties of micro-sized discoidal polymeric particles (DPPs) as lung-targeted drug delivery carriers. DPPs were prepared using a top-down fabrication approach and characterized by assessing size and zeta potential. They were labeled with zirconium-89 (89Zr), and bio-distribution studies and PET imaging were performed for 7 days after intravenous administration. Their hydrodynamic size was 2.8 ± 6.1 μm and average zeta potential was -39.9 ± 5.39 mV. At doses of 5, 12.5, and 25 mg/kg, they showed no acute toxicity in nude mice. Desferrioxamine (DFO)-functionalized 89Zr-labeled DPPs gave a decay-corrected radiochemical yield of 82.1 ± 0.2%. Furthermore, 89Zr-DPPs, from chelate-free labeling methods, showed a yield of 48.5 ± 0.9%. Bio-distribution studies and PET imaging showed 89Zr-DFO-DPPs to be mainly accumulated in the lungs and degraded within 3 d of injection. However, 89Zr-DFO-DPPs showed significantly low uptake in the bone. Overall, our results suggested micro-sized DPPs as promising drug delivery carriers for the targeted treatment of various pulmonary diseases.