Pharmacokinetics and tissue distribution of intranasal administration of rapamycin in rats.

Rapamycin has been shown to be effective in the treatment of a variety of neurological disorders, including epilepsy. Intranasal drug administration is a novel mode of drug delivery that bypasses the blood-brain barrier and numerous biological effects thereby entering the central nervous system directly. Thus, the objective of this study was to investigate the brain entrance efficacy of rapamycin following intranasal administration of rapamycin.First, we found that acute high-dose administration with a total dose of 0.326 mg of rapamycin in a novel dosage form produced few side effects on body weight, various organs, and nasal mucosa in rats. Then, we examined the distribution of drug concentrations in the brain, nasal mucosa, and blood using the above dosage form administered intranasally to rats at 0.04 mg/kg. We found that intranasal administration was significantly more efficacious than oral administration for rapamycin brain delivery. We also discovered gender differences in drug absorption following intranasal administration of rapamycin, wherein rapamycin exhibited faster systemic absorption in female rats compared to males. Our study demonstrated that intranasal administration of rapamycin is highly effective and low toxic, which may provide a new delivery option for rapamycin therapy in brain diseases.