To investigate the efficacy of needle-free injection (NFIT) through cervical lymph nodes as a novel strategy for drug delivery into the brain, and compare its efficiency for different drugs.

Using Evans blue as an injectant in vitro, the differences in drug diffusion between NFIT and needle-dependent injection were studied. By using sodium fluorescein as an injectant in vivo, the tissue distribution of sodium fluorescein in mice over time was evaluated after injection by different means before the dynamic changes of drug accumulation in the brain and lymphatic tissues were observed. Three representative drugs-cyanine5.5 (Cy5.5, a small molecule compound), Cy5.5-bovine serum albumin (Cy5.5-BSA, a protein drug), and Cy5.5-hyaluronic acid (Cy5.5-HA, a high molecular weight polymer) were used to evaluate the brain delivery efficiency of different drugs via NFIT.

In vitro diffusion experiments found a more rapid and uniform diffusion of drugs after NFIT while in vivo experiments showed that the delivery efficiency of fluorescein sodium through intracervical lymphatic NFIT was significantly higher in the cortex and hippocampus of mice than with traditional injection methods. A comparison of three representative drugs confirmed that intracervical lymphatic NFIT was an effective way to deliver small molecule compounds and protein drugs to the brain, but was not workable for polymers of high molecular mass.

Intracervical lymphatic NFIT can efficiently mediate the brain delivery of small molecules and protein drugs, which promises to be a drug delivery method for the application of such drugs to the brain.