UNSATURATED FREE FATTY ACIDS EFFECTS ON SYRINGIC ACID-ORGANOGELS STRUCTURAL AND BIOPHARMACEUTICAL PROPERTIES

Syringic acid (SA), a phenolic compound, has attracted interest due to its potential therapeutic effects on skin health. SA exhibits antioxidant, anti-inflammatory, and antimicrobial properties, which are beneficial in combating oxidative stress, reducing inflammation, and preventing skin microbial infections. The direct local application of bioactives to affected skin areas appears to be a safer option, reducing systemic exposure and thereby improving patient compliance. The development of new nanostructured carriers systems emerges as an innovative strategy to enhance the modulation of the permeation rate across the skin, thus favoring its bioavailability and penetration through the epidermis superficial layers. This study aimed to prepare, to characterize, and to evaluate rheological and biopharmaceutical properties of SA-loaded organogels with different unsaturated free fatty acids compositions. SA organogels were prepared by mixing an oil to aqueous phase (1:4 ratio v/v), with a mixture of 30 % (w/v) poloxamer 407 and oleic:linoleic acid or oleic acid:linolenic acid at 0.1 to 0.4% w/v. Results revealed that logP values ranged from 0.342 to 0.362, with the highest logP value observed for oleic acid. Rheological analysis was performed to determine the elastic (G′) and viscous (G′′) moduli, viscosity (η) and sol-gel temperature (Tsol-gel). G′ values were higher (~25x) than G′′, revealing a viscoelastic behavior, even after linoleic and linolenic acid incorporation. Tsol-gel was from ~7 to 9 °C, however SA incorporation shifted the transition process, increasing viscosity values. In vitro permeation assays through skin-model membranes showed higher SA permeation for OA-AL 0.2% (4.013 µg.cm⁻²) compared to OA-ALA 0.4% (2.574 μg.cm⁻²) and OA (1.460 μg.cm⁻²). As antioxidant effects, the half-maximum inhibitory concentration (IC50) related to SA in DPPH assays was detected as 66.37 μg.mL⁻¹. Additionally, ORG formulations presented low cytotoxic effects in keratinocytes and fibroblasts. Those results demonstrated the potential use of nanostructured systems such as organogels as promising strategies for SA skin delivery.

This work was supported by CNPq (# 308819/2022-5).