Assessment of intranasal permeability and pharmacological activity of glyburide-loaded nanosuspension formulation for Alzheimer’s disease

Glyburide is an anti-diabetic drug with promising potential implications for Alzheimer’s disease. This study evaluated the permeability and activity of glyburide via intranasal administration in Alzheimer’s disease using both in vivo and ex vivo studies. A glyburide nanosuspension, was used as the drug delivery system. Stability studies demonstrated that the nanosuspension formulation presented suitable stability during in vitro and in vivo studies. The chosen in vivo glyburide dose demonstrated a non-toxic profile via MTT. Additionally, the in vitro permeability of the nanosuspension was assessed. Pharmacological activity was further evaluated through in vivo behavioural tests, including the Morris water maze and novel object recognition tests, and amyloid-beta levels were measured in mice brain tissues with ELISA. Ex vivo quantification of glyburide concentration in various tissues was also conducted. In vitro permeability studies showed that the nanosuspension formulation significantly enhanced permeability of glyburide. In vivo behavioural tests demonstrated that the nanosuspension formulation yielded favourable and promising outcomes even it was administered intranasally. This study suggests that, through the solubility enhancement provided by nanocrystal technology increased the bioavailability of glyburide comparing the intranasal administration of glyburide, leading to improve in vivo activity compared to the raw glyburide suspension in the treatment of Alzheimer’s disease.