Highly efficient organ-targeting transport through the ventral midline interstitial channels injection: a new development of interstitium

Abstract

How to improve the drugs bioavailability has always been a hot and difficult topic. Conventional drug delivery methods, such as oral administration and the blood circulation system, suffer from issues such as low targeting efficiency, low bioavailability, and high side effects. Recently, interstitium has gradually been recognized as an important new organ. Interstitial injection allows small molecules to move through interstitial channels with interstitial fluid flow and be transported to organs, providing new possibilities for drug delivery. In this study, using fluorescein sodium as a drug model, we systematically investigated the distribution of the fluorescein sodium in organs and body surface of the rats after ventral midline interstitial channels injection. In addition, we observed the microstructure of the ventral midline interstitial channels of abdominal wall and the effects of channels ligation on fluorescein sodium delivery and target organs, to explore the mechanism of interstitial injection. We found that fluorescein sodium can be efficiently transported to the uterus and ovaries along the ventral midline interstitial channels, and the parallel fibers and interconnected interstitial spaces of the channels facilitate long-distance transport of solutes. Additionally, the blockage of the transmission through those channels had results in a significant decrease in targeted transport efficiency over long distances, a decrease in oestrogen levels, organ coefficients, and body weights in female rats. Therefore, the ventral midline interstitial channels with free fluid flow may be a potential communication pathway between body surface and organs. These findings have significant value in the development of drug delivery.