Gellan-Based Hydrogel as a Drug Delivery System for Caffeic Acid Phenethyl Ester in the Treatment of Oral Candida albicans Infections

Abstract

Candida albicans can cause various types of oral infections, mainly associated with denture stomatitis. Conventional therapy has been linked to high recurrence, toxicity, and fungal resistance, necessitating the search for new drugs and delivery systems. In this study, caffeic acid phenethyl ester (CAPE) and gellan gum (GG) were studied as an antifungal agent and carrier system, respectively. First, we observed that different GG formulations (0.6 to 1.0% wt/vol) were able to incorporate and release CAPE, reaching a controlled and prolonged release over 180 min at 1.0% of GG. CAPE-GG formulations exhibited antifungal activity at CAPE concentrations ranging from 128 to >512 µg/mL. Furthermore, CAPE-GG formulations significantly decreased the fungal viability of C. albicans biofilms at short times (12 h), mainly at 1.0% of GG (p < 0.001). C. albicans protease activity was also reduced after 12 h of treatment with CAPE-GG formulations (p < 0.001). Importantly, CAPE was not cytotoxic to human keratinocytes, and CAPE-GG formulations at 1.0% decreased the fungal burden (p = 0.0087) and suppressed inflammation in a rat model of denture stomatitis. Altogether, these results indicate that GG is a promising delivery system for CAPE, showing effective activity against C. albicans and potential to be used in the treatment of denture stomatitis.

Gellan Gum as a Unique Microbial Polysaccharide: Its Characteristics, Synthesis, and Current Application Trends

“…There have been several cutting-edge advancements in the use of GG to develop responsive systems in the field of biomedical applications ( Table 9 ). The latest developments in the use of GG in various biomedical fields demonstrate its ability to advance drug delivery [ 107 , 110 , 111 , 112 ], tissue engineering [ 113 , 114 ], wound healing [ 115 , 116 ], and diagnostics [ 111 , 117 ]. The responsive nature of GG enables the development of specific systems that react to particular physiological signals, enhancing their efficiency and flexibility in different biomedical scenarios.…”

“…Smart drug delivery systems GG has been utilized in the development of advanced drug delivery systems that react to different stimuli, like temperature, pH, or specific ions. These systems can offer the controlled and targeted delivery of therapeutic substances, enhancing the effectiveness of drugs while reducing potential negative reactions [107,[110][111][112] Temperature-responsive hydrogels Hydrogels composed of GG have been formulated to demonstrate temperature-sensitive properties, enabling them to transition between sol and gel states based on temperature variations. This characteristic is especially valuable in scenarios where in situ gelation is required, like injectable hydrogels for minimally invasive drug delivery or tissue engineering.…”

“…Utilizing the unique properties of GG, it is possible to develop sensing platforms capable of detecting particular biomolecules or variations in physiological conditions. [111,112,114,117,126] Combination with nanoparticles GG can be combined with nanoparticles, like drug-loaded nanoparticles or imaging agents, to develop multifunctional responsive systems with improved therapeutic or diagnostic capabilities.…”