Biodegradable radiopaque polymeric particles for computed tomography-guided intraperitoneal drug delivery

An iodinated hydrophobic oil containing the 2,3,5-triiodobenzoate moiety was encapsulated in biodegradable poly(lactic acid)-based polymer particles using a solvent emulsion-evaporation technique that provided control over particle size. The hydrophobic iodinated oil served a dual function as radiopaque contrast agent for particle quantification using dual-energy x-ray computed tomography (DECT) imaging and furthermore as solvent for the chemotherapeutic drug paclitaxel (PTX), establishing a novel theranostic system. Release kinetics of PTX was studied in fetal bovine serum over seven days demonstrating sustainable drug release over the entire period, with cumulative release mainly depending on particle diameter. Intraperitoneal administration of a therapeutic dosage of radiopaque spheres in mice provided sufficient iodine contrast to track biodistribution and clearance over 18 days. Importantly, imaging showed unexpected particle aggregation in vivo with about 50% clearance over 18 days, emphasizing the value of real-time distribution assessment as a complementary method to conventional ex-vivo histology. A proof of concept of longitudinal dual imaging using single-photon emission CT (SPECT)/DECT was demonstrated in a mouse model of colorectal cancer with intraperitoneal metastases following a single intraperitoneal dose of PTX or PTX-loaded particles. Treatment response was monitored using SPECT, while particle distribution was tracked by DECT. This theranostic approach integrates controlled intraperitoneal drug delivery with non-invasive quantitative DECT-based imaging and may improve treatment precision and therapeutic outcomes.