Development of Propolis (Apis trigona)-loaded Nanoemulgel for Improved Skin Penetration of Caffeic Acid: The Effect of Variation of Oleic Acid Concentration

BACKGROUND: Propolis contains caffeic acid compounds, which are proven to have pharmacological effects as an anti-inflammatory. However, its effectiveness is hampered by the poor solubility of caffeic acid. Here, we report developing the nanoemulgel approach containing propolis extract as an active ingredient and oleic acid as a permeation enhancer for transdermal delivery of caffeic acid. AIM: This study aims to determine the effect of oleic acid concentration on increasing caffeic acid permeation in the skin and obtain a nanoemulgel formula with desired physical characteristics and stability. MATERIALS AND METHODS: Propolis was macerated with 70% ethanol; the total phenolic content was measured by ultraviolet–visible spectrophotometer, and the levels of caffeic acid in the extracts and nanoemulgel preparations were finally determined using ultra-fast liquid chromatography. Formulas were made using various concentrations of oleic acid, namely, 1.25%w/w (Formula F1); 2.5%w/w (Formula F2); 5%w/w (Formula F3), respectively; and 1.25%w/w without propolis extract (Formula F4) as a comparison. RESULTS: The results obtained from analysis of variance statistical exhibited that the difference in oleic acid concentrations in four formulas significantly affected (p < 0.05) particle size, polydispersity index, spreadability, adhesion, freeze-thaw, permeation, and retention test. However, there was no significant difference (p > 0.05) on pH and viscosity before and after 4 weeks of storage and zeta potential test. The highest amount of permeation and retention was found in F3 and F2, respectively, and all formulas tended to follow zero-order drug release kinetics. Furthermore, the results showed that the number of percent’s permeated in a row was 3.74% (F1); 5.58% (F2); 11.67% (F3), and F2 was the formula with the most optimal retention amount with a percentage of 43.13% at 24 h. CONCLUSION: This study shows a promising delivery system for increasing the effectiveness of natural lipophilic compounds to treat inflammation in the skin.