Development of 64Cu-DOX/DOX-loaded chitosan-BSA multilayered hollow microcapsules for selective lung drug delivery

To selective delivery of high dosage of doxorubicin (DOX) to the lung via I.V injection, it was loaded into chitosan-BSA multilayered hollow microcapsules fabricated based on the CaCO3 template. The 64Cu-DOX radiotracer was also loaded along with cold DOX for the evaluation of the biodistribution. Hollow microcapsules were non-toxic, compatible with red blood cells, and did not change the blood coagulation time. The drug content of drug-loaded hollow microcapsules was %55–60 and their toxicity depends on the drug release rate. PET-CT images showed that, unlike unloaded DOX, the majority of the loaded drug (>%75) was delivered to the lung by the hollow microcapsules and then sustainably released from microcapsules into the lungs. The ratios of loaded drug accumulated in the lungs to the liver were 5.2, 2.52, 0.28, and 0.14, at 1, 4, 14, and 24 h post-injection, respectively. These ratios for injection of the unloaded drug were 0.04, 0.01,0.01, and 0.006 at the same time intervals. The results showed that the fabricated hollow microcapsules are capable to carry a high dose of the drug to the lungs. Chitosan-BSA hollow microcapsules (size> 5 μm) were fabricated and loaded with the 64Cu-DOX radiotracer and cold DOX. Biodistribution studies showed that the majority of the loaded drug was delivered to the lungs after intravenous injection. [Display omitted] •Chitosan-BSA multilayered hollow microcapsules were fabricated based on CaCO3 template.•64Cu-DOX and cold DOX were loaded into the hollow microcapsules (%DC = 55–60).•Hollow microcapsules were non-toxic, compatible with red blood cells and did not change the blood coagulation time.•The majority of the loaded drug (>%75) was delivered to the lung by the hollow microcapsules.•The delivered drug was sustainably released from microcapsules into the lungs and then washed out from the lungs over time.