Potential Unlocking of Biological Activity of Caffeic Acid by Incorporation into Hydrophilic Gels

Abstract

Caffeic acid, a phenolic compound with antioxidant and antimicrobial properties, shows promise in the dermatological field. The research aimed to incorporate caffeic acid into hydrophilic gels based on poloxamer 407, carbomer 980, and their mixture in order to enhance its biological activity. Different gel formulations were prepared using different concentrations of these polymers to optimize caffeic acid release characteristics. The results showed that increasing the concentration of polymeric materials increased the viscosity and slowed down the release of caffeic acid. The antioxidant and antimicrobial activities of the gels were assessed. The results confirmed the potential of hydrophilic gels as delivery systems for caffeic acid, with formulations showing antimicrobial activity against Gram-positive Staphylococcus aureus bacteria and antifungal activity against Candida albicans fungus. This study provides a perception of the development of new semi-solid caffeic acid-based formulations for therapeutic and cosmetic applications.

Keywords: antimicrobial; caffeic acid; carbomer; hydrogel; poloxamer.

Figure 1

Viscosity dependence of carbomer gels with caffeic acid on different pH ranges (CP50, CP75, CP1; n = 3, mean ± SD).

Figure 2

Temperature dependence of viscosity of carbomer gels containing caffeic acid at pH 5.5 ± 0.3 (CP50, CP75, CP1). Measurements were performed at 23 °C, 32 °C, and 37 °C (n = 3, mean ± SD).

Figure 3

Viscosity dependence on temperature of Poloxamer 407 and Poloxamer 407 + Carbomer 980 gels with caffeic acid (pH 5.5 ± 0.3) at different polymer concentrations: (a) P12, (b) PG1, (c) P15, (d) PG2, (e) P18, (f) PG3 (n = 3, mean ± SD).

Figure 3

Viscosity dependence on temperature of Poloxamer 407 and Poloxamer 407 + Carbomer 980 gels with caffeic acid (pH 5.5 ± 0.3) at different polymer concentrations: (a) P12, (b) PG1, (c) P15, (d) PG2, (e) P18, (f) PG3 (n = 3, mean ± SD).

Figure 4

Solubility of caffeic acid in purified water, HCl (pH = 1.2), PBS (pH = 6.8), and 30% (v/v) ethanol (n = 3, mean ± SD).

Figure 5

Release kinetics of caffeic acid from gel formulations based on the square root of time (SQRT), following the Higuchi equation. The formulations include (a) Carbomer 980-based gels (CP50, CP75, CP1), (b) P407-based gels (P12, P15, P18), and (c) mixtures of these polymers (PG1, PG2, PG3), (n = 3, mean ± SD).

Figure 5

Release kinetics of caffeic acid from gel formulations based on the square root of time (SQRT), following the Higuchi equation. The formulations include (a) Carbomer 980-based gels (CP50, CP75, CP1), (b) P407-based gels (P12, P15, P18), and (c) mixtures of these polymers (PG1, PG2, PG3), (n = 3, mean ± SD).

Figure 6

Antioxidant activity of experimental gels in vitro release fractions (acceptor medium) after 6 h by the DPPH method (n = 3, mean ± SD).

Figure 7

HaCaT cell viability STE test using different concentrations of caffeic acid (medium 30% ethanol). HaCaT cells were treated with different concentrations of caffeic acid (25–300 μg/mL) for 30 min (n = 3, mean ± SD).

Figure 8

HaCaT cell viability using different concentrations of H₂O₂ (100–200 μM) and caffeic acid (0.05–0.3 mg/mL). HaCaT cells were treated with different concentrations of H₂O₂ and caffeic acid for 24 h (n = 3, mean ± SD). The asterisks (*) indicate statistically significant differences (p < 0.05) between the H₂O₂ treatment group and the groups treated with caffeic acid.