Design and Optimization of Beta-Caryophyllene Nanoemulgel for Enhanced Antihyperlipidemic Activity: A Response Surface Approach.

Publication date: Jun 29, 2026

After COVID-19, there has been a significant rise in cardiovascular complications, including an increased risk of myocardial infarction, primarily associated with elevated lipid concentrations in the bloodstream. β-caryophyllene (β-CP), a naturally occurring compound with a bicyclic sesquiterpene structure found in various plants and essential oils, has demonstrated inhibitory activity against hyperlipidemia. One of the most inventive solutions for problems with weak absorption and limited solubility is nanoemulsion. In this study, β-CP nanoemulsion was prepared by a high-energy method followed by high-pressure homogenization (Panda Plus 2000) using Tween 80 and PEG 400 as surfactant and cosurfactant, respectively. The process was optimized using the Box-Behnken design, and the optimized nanoemulsion was incorporated into an in situ gel prepared by the cold method with poloxamer 407. Various parameters of the improved nanoemulsion were evaluated, revealing an average particle size (61. 77 nm), Zeta potential (-28. 3 mV), and PDI (0. 238). It enhanced solubility up to fivefold, making it acceptable for absorption into the systemic circulation via intranasal delivery. The improved in situ gel had good viscosity, spreadability, gelation, and mucoadhesive strength for ionic contact with the nasal mucosa. The in vitro release study showed that the optimized in situ gel achieved the highest drug release of 98. 71% within 12 hours. The improved solubility and sustained release were the result of the combined effect of nanoemulsion encapsulation and thermosensitive gelation. This dual system increased nasal residence time, enhanced absorption, and reduced side effects. Optimization using the Box-Behnken design ensured a stable and reproducible formulation. The findings suggest that an in situ nasal nanogel could be the most efficient approach for delivering β-cp into the systemic circulation for the treatment of hyperlipidemia.

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Original Article