Permeation enhancement effects of leaf materials from different aloe species on in vitro and ex vivo nasal epithelial models

Introduction: The nasal route of drug administration offers an alternative way for oral drug delivery and has the benefit of avoiding first-pass metabolism through drug delivery directly into the systemic circulation. The drug absorption enhancing effects of selected aloe leaf materials have been shown across various delivery routes, but their efficacies in this regard across nasal epithelia have not yet been investigated. The aim of this study was to determine the effects of gel and whole leaf extract materials from three selected aloe species (Aloe vera, Aloe ferox and Aloe muth-muth) on FITC-dextran ۴۴۰۰ permeation across two nasal epithelial models. Methods: Permeation of FITC-dextran ۴۴۰۰ and histological studies were conducted on both RPMI ۲۶۵۰ cell layers and excised sheep nasal mucosa, while toxicity studies were conducted using a neutral red assay on the RPMI ۲۶۵۰ cell model. Results: Significantly increased (P ≤ ۰.۰۵) apparent permeability coefficient (Papp) values of FITC-dextran ۴۴۰۰ in the presence of the aloe materials as compared to the control were found with all three aloe species at the highest concentrations (۱.۵% and ۳% w/v) in the RPMI ۲۶۵۰ cell line, while only Aloe muth-muth at the highest concentration exhibited significantly (P ≤ ۰.۰۵) higher Papp values across the excised tissue model. Histological and neutral red analysis showed that Aloe vera materials exhibited detrimental effects, Aloe muth-muth only showed slight effects on cell viability and Aloe ferox exhibited no effect on the nasal epithelium. Conclusion: This in vitro study showed for the first time the potential of Aloe ferox and Aloe muth-muth leaf materials to enhance nasal drug delivery without causing damaging effects on the epithelium, while Aloe vera enhanced nasal drug delivery with detrimental effects as determined by means of cytotoxicity assays and histological analysis.