Systemic Administration of Polyelectrolyte Microcapsules: Where Do They Accumulate and When? In Vivo and Ex Vivo Study

Abstract

Multilayer capsules of 4 microns in size made of biodegradable polymers and iron oxide magnetite nanoparticles have been injected intravenously into rats. The time-dependent microcapsule distribution in organs was investigated in vivo by magnetic resonance imaging (MRI) and ex vivo by histological examination (HE), atomic absorption spectroscopy (AAS) and electron spin resonance (ESR), as these methods provide information at different stages of microcapsule degradation. The following organs were collected: Kidney, liver, lung, and spleen through 15 min, 1 h, 4 h, 24 h, 14 days, and 30 days after intravenous injections (IVIs) of microcapsules in a saline buffer at a dosage of 2.5 × 109 capsule per kg. The IVI of microcapsules resulted in reversible morphological changes in most of the examined inner organs (kidney, heart, liver, and spleen). The capsules lost their integrity due to degradation over 24 h, and some traces of iron oxide nanoparticles were seen at 7 days in spleen and liver structure. The morphological structure of the tissues was completely restored one month after IVI of microcapsules. Comprehensive analysis of the biodistribution and degradation of entire capsules and magnetite nanoparticles as their components gave us grounds to recommend these composite microcapsules as useful and safe tools for drug delivery applications.

Keywords

• polymer microcapsules
• magnetite nanoparticles
• biodistribution
• magnetic resonance imaging
• electron spin resonance spectroscopy
• histological examination
• atomic absorption spectroscopy
• intravenous injections