Mesoporous Aerogel Microparticles Injected into the Abdominal Cavity of Mice Accumulate in Parathymic Lymph Nodes.

Gábor Király,József Kalmár,István Fábián,Zoltán Hargitai,Gábor Szemán-Nagy,John Chinonso Egu,Ilona Kovács

doi:10.3390/ijms22189756

Gábor Király, József Kalmár + Show 5 more

Open Access

https://doi.org/10.3390/ijms22189756

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Abstract

Mesoporous aerogel microparticles are promising drug delivery systems. However, their in vivo biodistribution pathways and health effects are unknown. Suspensions of fluorescein-labeled silica–gelatin hybrid aerogel microparticles were injected into the peritoneum (abdominal cavity) of healthy mice in concentrations of 52 and 104 mg kg−1 in a 3-week-long acute toxicity experiment. No physiological dysfunctions were detected, and all mice were healthy. An autopsy revealed that the aerogel microparticles were not present at the site of injection in the abdominal cavity at the end of the experiment. The histological study of the liver, spleen, kidneys, thymus and lymphatic tissues showed no signs of toxicity. The localization of the aerogel microparticles in the organs was studied by fluorescence microscopy. Aerogel microparticles were not detected in any of the abdominal organs, but they were clearly visible in the cortical part of the parathymic lymph nodes, where they accumulated. The accumulation of aerogel microparticles in parathymic lymph nodes in combination with their absence in the reticuloendothelial system organs, such as the liver or spleen, suggests that the microparticles entered the lymphatic circulation. This biodistribution pathway could be exploited to design passive targeting drug delivery systems for flooding metastatic pathways of abdominal cancers that spread via the lymphatic circulation.

Highlights

Nowadays, numerous studies have focused on the biomedical applications of aerogels [1]
One of the most important findings of the autopsy is that the hybrid aerogel microparticles (FSGM) were not present at the site of injection or anywhere visible in the abdominal cavity at the end of the experiment
We propose that the good biocompatibility of the silica–gelatin aerogel microparticles reported in this study is the combined consequence of their high gelatin content and the significant increase in the size of the porous material, i.e., the formulation of microparticles instead of nanoparticles

Summary

Introduction

Numerous studies have focused on the biomedical applications of aerogels [1]. Aerogels are a group of solid materials of high porosity (90–99%), low density (0.005–0.50 g cm−3) and high specific surface area (300–1000 m2 g−1). They have a highly interconnected open pore structure with adjustable pore size and morphology. Inorganic oxide and biopolymer aerogels are promising candidates for developing novel drug delivery systems (DDS) [2,3]. Several biopolymer and hybrid aerogels have been investigated as drug delivery systems [5,6,7,8]. Aerogels can be formulated into microparticles, 10–100 μm in diameter [9,10,11,12,13]. Microparticles injected into the abdominal cavity could possibly follow abdominal tumor cells that metastasize to the parathymic lymph nodes via the lymphatic circulation, providing passively targeted drug delivery [12,14]

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