Visual tracing of diffusion and biodistribution for amphiphilic cationic nanoparticles using photoacoustic imaging after ex vivo intravitreal injections

Abstract

Xu Xu,* Zhaokang Xu,* Junyi Liu, Zhaoliang Zhang, Hao Chen, Xingyi Li, Shuai Shi Institute of Biomedical Engineering, School of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China *These authors contributed equally to this work Abstract: To visually trace the diffusion and biodistribution of amphiphilic cation micelles after vitreous injection, various triblock copolymers of monomethoxy poly(ethylene glycol)–poly(ε-caprolactone)–polyethylenimine were synthesized with different structures of hydrophilic and hydrophobic segments, followed by labeling with near-infrared fluorescent dye Cyanine5 or Cyanine7. The micellar size, polydispersity index, and surface charge were measured by dynamic light scattering. The diffusion was monitored using photoacoustic imaging in real time after intravitreal injections. Moreover, the labeled nanoparticle distribution in the posterior segment of the eye was imaged histologically by confocal microscopy. The results showed that the hydrophilic segment increased vitreous diffusion, while a positive charge on the particle surface hindered diffusion. In addition, the particles diffused through the retinal layers and were enriched in the retinal pigment epithelial layer. This work tried to study the diffusion rate via a simple method by using visible images, and then provided basic data for the development of intraocular drug carriers. Keywords: visible tracing, cavum vitreum, biodistribution, diffusion rate

Keywords

• photoacoustic imaging
• intravitreal injection
• amphiphilic cationic nanoparticle
• tracing