| Summary: | <i>Aloe vera</i> gel and whole leaf materials, as well as polysaccharides, precipitated from the gel, have previously been shown to enhance macromolecular drug delivery across epithelial tissues. This study investigated the effectiveness of microparticle formulations prepared from <i>A. vera</i> polysaccharides for nasal delivery of insulin across excised sheep olfactory and respiratory nasal epithelial tissues. An emulsion-solvent evaporation technique was used to prepare two insulin microparticle formulations, namely one containing Eudragit<sup>®</sup> L100 and <i>A. vera</i> polysaccharides and one containing <i>A. vera</i> polysaccharides only. In addition, an ionic gelation technique was used to prepare an insulin microparticle formulation with <i>A. vera</i> polysaccharides, where calcium chloride was used as a cross-linker. The microparticle formulations were evaluated in terms of drug content (assay), particle size, drug release (dissolution), ex vivo drug permeation, and histology. The microparticle formulations exhibited statistically significantly higher insulin delivery across excised sheep olfactory and respiratory nasal epithelial tissues compared to that of the control group (insulin alone). In conclusion, the use of <i>A. vera</i> polysaccharides in microparticle formulations significantly improved nasal insulin delivery. Therefore, <i>A. vera</i> polysaccharide containing microparticles showed high potential to enhance systemic bioavailability and delivery into the brain of macromolecular drugs such as insulin after intranasal administration.
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