Rutin and Scopoletin Co-Loaded Niosomes for Intranasal Brain Delivery: Formulation Optimization and Ex Vivo Evaluation

Introduction/Objective: Rutin (R) and scopoletin (S) are natural flavonols, which have been shown to reduce heart disease, improve blood circulation, reduce inflammation, and even prevent diabetes. Certain physicochemical properties, such as poor solubility and poor oral bioavailability of RS, diminish their therapeutic effectiveness. This study aims to develop the RS niosomes formulation (RS-Ns-Opt) to improve the bioavailability and solubility of RS. Methods: Lipid-derived vesicles enclosing RS were developed by the thin-film hydration method, whereas surfactants and cholesterol formed the RS niosome. RS-Ns-Opt were developed and evaluated using the thin-film hydration method, drug release, DPPH assay, confocal laser scanning microscopy (CLSM), ex vivo nasal mucosa permeation, UV analysis, and differential scanning calorimetry (DSC). Results: Nanosize vesicles (55.22 nm) of RS-Ns-Opt were formed within an acceptable polydispersity index (PDI) (0.234). In contrast, the entrapment efficiency of R (72.64%) and S (72.44%) indicates efficient uniformity and automatic surface interaction. Moreover, RS-Ns-Opt exhibited notable drug release (79.96 ± 0.68%) and effective antioxidant activity (70.11 ± 3.07%) compared with RS suspension drug release (23.49 ± 2.11%) and antioxidant potential (75.59 ± 0.75%). Discussion: The CLSM study found that RS-Ns-Opt loaded with rhodamine B showed superior penetration compared to the control. Conclusion: The planned RS-Ns-Opt niosomes can improve the bioavailability of RS and are expected to gain wide consideration in the near future for healthcare applications.