Formulation and Optimization of Intra Nasal Niosomal Gel of Kynurenic Acid: In Vitro in Vivo Characterization

Abstract

Kynurenic acid's (KNA) inability to cross the blood brain barrier (BBB) severely limits its usage as a neuroprotective drug, despite the fact that it may have significant therapeutic effects in neurological illnesses. Drug delivery devices are one of the new avenues we're exploring as a means for KNA to enter the brain. Due to its low absorption when taken orally, medication formulation faces a significant hurdle. Here, nasal drug delivery has emerged as a popular alternate method for increasing medication bioavailability. In light of this, the current investigation set out to increase KNA bioavailability by means of an intranasal formulation based on niosomal technology. Rapid onset and evasion of first-pass metabolism are both offered by the nasal route, whereas niosomes protect hydrophilic medicines inside their core. For the purpose of determining entrapment efficiency, particle size, and in vitro drug release, niosomes were synthesized by combining lipid, nonionic surfactant, and cholesterol in distinct ratios. With a vesicle size of 248.51±1.54nm, the optimized niosomal formulation demonstrated a superior drug content (DC) of 98216±0.11% and an entrapment efficiency (EE) of 89.23±0.35. The formulation also contained cholesterol in an equal proportion (1:1). A value of 24 minutes was shown in the in vitro drug diffusion testing, indicating that the formulation exhibited prolonged activity. Gelation occurred at 37 ⁰C, which is the body's physiological temperature, and the optimum in situ gel, which contained 1:2 carbopol 934 and benzalkonium chloride, had a t90 value of 24 hours, indicating prolonged activity. In comparison to KNA oral suspension, the results showed that the KNA-loaded niosomal gel had a much higher relative bioavailability and improved drug penetration through the nasal mucosa