New diffusion media to study intranasal drug delivery system ex vivo

Intranasal administration is a drug delivery approach to provide a non-invasive pharmacological responsein the central nervous system (CNS) with relatively small peripheral side effects. Ex vivo experimentsare valuable tools to study the function and behavior of biological systems in a controlled and simplifiedmanner before proceeding to in vivo and clinical studies. Excised tissues, in particular, provide a meansof evaluating the diffusion and toxicity of intranasal drug delivery systems (IN-DDSs). However, reliablediffusion investigations require the use of healthy and live tissues, as the metabolic stability and permeationmechanisms are highly dependent on tissue cell viability. Currently, despite the wide range of therapeuticsbeing developed as IN formulations, there is no validated protocol to test the diffusion of nasal excisedtissues, which raises concerns about potential tissue damage that could adversely affect the diffusion rate.Therefore, there is a need for more reliable methods to simulate drug penetration through the nasal epithelium.Here, we applied a new approach using Krebs-Henseleit buffer (KHB) solution along with simulatednasal fluid (SNF) in a Franz’s diffusion cell to study IN-DDSs. We used KHB solution because of its abilityto supply glucose to the cells which serves as a novel ex vivo diffusion medium to maintain the viability ofthe tissue during the experiment. Based on diffusion rate and histopathological endpoints, KHB solution canbe a substituent solution to the commonly used SNF for such drug delivery systems.