Cyclodextrin Hydrogels Deliver Skin-Brightening Actives and Antifungal Protection in One Formulation

Cosmetic chemists have long wrestled with an awkward truth: many of the most celebrated skin-brightening ingredients are also among the most fragile. Arbutin degrades and oxidizes on the shelf, niacinamide can sting sensitive skin at high concentrations, and benzoic acid, a workhorse antimicrobial preservative, barely dissolves in the watery bases that dominate modern skincare. A team at Hannam University in Daejeon, South Korea, reporting in Frontiers in Materials, has now tackled all three problems at once by packing these actives into molecular cages of β-cyclodextrin and then dispersing those cages throughout a hydroxyethyl cellulose hydrogel. The resulting lotions, formulated at pH 5.53 and 5.55, flowed like a well-behaved cream under shear and, in laboratory assays, visibly inhibited the growth of the fungus Candida albicans.

The core of the strategy is supramolecular chemistry. β-cyclodextrin is a ring-shaped sugar molecule with a hydrophobic interior cavity and a hydrophilic exterior, which allows it to swallow poorly compatible guest molecules while remaining happily soluble in water. When an active ingredient slips inside the cavity, its electronic environment changes, its crystalline structure is disrupted, and its direct contact with skin is reduced. The researchers exploited this by preparing three separate inclusion complexes through coprecipitation: arbutin and niacinamide were each combined with β-cyclodextrin at a 1:1 molar ratio, while benzoic acid was complexed at approximately a 2:1 guest-to-host ratio. Ethanolic solutions of each guest were slowly added to aqueous β-cyclodextrin under stirring at 25 °C, and the precipitated complexes were filtered, washed, and vacuum-dried below 50 °C for 24 hours.

Confirming that complexation had actually occurred required an unusually thorough analytical battery. Ultraviolet-visible spectroscopy revealed telltale shifts in absorption maxima: pure arbutin absorbs at 220 and 281 nanometers, but after complexation the peaks moved to 215 and 262 nanometers, a hypsochromic or blue shift consistent with altered electronic environments inside the host cavity. Niacinamide, by contrast, showed a bathochromic or red shift, while benzoic acid’s peaks at 226 and 271 nanometers shifted toward shorter wavelengths. Scanning electron microscopy added morphological corroboration. Where the pure ingredients displayed regular crystalline shapes, the inclusion complexes formed entirely new structures: rod-like aggregates for the arbutin complex, angular columnar morphologies for the niacinamide complex, and angular rectangular structures for the benzoic acid complex, none of which resembled the simple physical mixtures of the same components.

Thermal analysis told perhaps the most persuasive story. Pure benzoic acid is notoriously volatile, losing 98.58 percent of its mass by 179.7 °C as it sublimates and vaporizes. Once trapped inside β-cyclodextrin, however, its initial mass loss was delayed to approximately 130 °C and its second degradation stage shifted from roughly 204 °C to 268 °C, with final decomposition not occurring until about 509 °C. The niacinamide complex showed an even more dramatic stabilization, pushing its second degradation stage from around 240 °C to approximately 350 °C, an effect the authors attribute to robust hydrogen bonding between the amide group and the host molecule. The arbutin complex delayed its initial mass loss from 156 °C to 177 °C. Differential scanning calorimetry reinforced the picture: the sharp melting endotherms of all three pure guests, at roughly 200–205 °C for arbutin, 130–135 °C for niacinamide, and 120–125 °C for benzoic acid, vanished entirely in the inclusion complexes, replaced by broad thermal events signaling a loss of crystalline character.

Proton nuclear magnetic resonance spectroscopy provided the molecular-level view. In the complexed samples, the aromatic and pyridine proton signals of the guest molecules broadened substantially and became less distinguishable, while the primary hydroxyl signal of β-cyclodextrin, initially split at 4.45 to 4.54 ppm, shifted upfield and collapsed into a distinct triplet around 4.35 ppm. For benzoic acid, the aromatic protons shifted slightly upfield, which the authors suggest may reflect shielding within the hydrophobic cavity, while the carboxylic proton moved marginally downfield, possibly due to hydrogen bonding with the host’s exterior hydroxyl groups. The researchers are careful to note that these converging lines of evidence support, but do not definitively prove, complete encapsulation; techniques such as powder X-ray diffraction and two-dimensional ROESY NMR would be needed to pin down the exact inclusion geometry.

With the complexes in hand, the team built the delivery vehicle. Hydroxyethyl cellulose was dissolved in water alongside glycerin, 1,3-butylene glycol, and a trace of citric acid, heated to 50 °C to form a homogeneous gel base, then cooled to 30 °C before the inclusion complex powders were stirred in. Two formulations emerged: No. 4 combined the arbutin and benzoic acid complexes, while No. 5 paired the niacinamide and benzoic acid complexes. Both finished lotions registered pH values of 5.53 and 5.55, sitting squarely at the natural acidity of human skin, a detail that matters both for minimizing irritation and for preserving the chemical stability of actives that prefer slightly acidic conditions.

Rheological testing revealed classic pseudoplastic, or shear-thinning, behavior. Measured with a cone-and-plate viscometer across shear rates of roughly 0.9 to 300 per second, formulation No. 4 dropped in apparent viscosity from 5,953 to 463.4 centipoise, a 92.2 percent reduction, while No. 5 fell from 6,284 to 278.8 centipoise, a 95.6 percent drop. At the highest rotational speed of 100 rpm, No. 5 was about 39.9 percent less viscous than No. 4. This profile is exactly what a topical product wants: thick enough at rest to hold its structure, thin enough under the shear of a fingertip to spread easily. The authors caution, however, that each formulation was measured as a single batch with no statistical hypothesis testing, so these flow data are descriptive rather than statistically validated. Texture profile analysis, performed on three independent batches per formulation, showed that No. 5 was significantly harder (75.28 versus 68.01 grams, p = 0.0019), more adhesive (−59.40 versus −44.64 gram-seconds, p = 0.0065), and slightly less springy and cohesive, while resilience differences were not statistically significant.

The biological payoff came from the disk diffusion assays. Paper disks loaded with the functional hydrogels and placed on agar plates inoculated with Candida albicans produced clear inhibition zones after 24 hours at 35 °C, whereas the plain hydroxyethyl cellulose control showed no measurable activity beyond the disk itself. Formulation No. 5 generated a significantly larger zone, 1.20 ± 0.08 centimeters, than No. 4, at 0.90 ± 0.05 centimeters (p = 0.0087). The authors interpret this cautiously: because the two formulations differ in overall composition, the difference cannot be attributed specifically to benzoic acid alone. Moreover, no control disks containing free benzoic acid or an uncomplexed physical mixture were included, so the individual contributions of the preservative, the cyclodextrin, and the polymer matrix cannot yet be disentangled. The assay also tested only one fungal species and did not determine minimum inhibitory or fungicidal concentrations.

Qualitative release experiments rounded out the evaluation. When one gram of each lotion was dispersed in 50 milliliters of distilled water for one hour and the supernatant analyzed by UV-visible spectroscopy, both functional formulations produced distinct absorption peaks, at 217 and 262 nanometers for No. 4 and 220 and 280 nanometers for No. 5, while the blank controls showed none. This confirms that the actives become available in the aqueous phase as the gel hydrates, though the overlapping absorption bands of the co-encapsulated ingredients prevented peak-by-peak assignment, and the single timepoint design stops short of establishing release kinetics. Thermogravimetric analysis of the finished gels showed that the principal degradation stage shifted to approximately 255 °C for No. 4 and 250 °C for No. 5, higher than the basic hydrogel, suggesting that the embedded complexes reinforce the matrix itself, likely through hydrogen bonding between hydroxyethyl cellulose and the exterior hydroxyl groups of β-cyclodextrin.

The authors are candid about what remains undone. Encapsulation efficiency and guest loading were never quantified because free and complexed guest molecules were not separated before analysis. Long-term storage stability, formal dermatological safety testing such as cytotoxicity assays or human patch testing, and quantitative chromatographic release profiling all await future work. Yet the study’s central demonstration stands: multiple cosmetic actives and a poorly water-soluble preservative can be co-delivered through a single cyclodextrin-hydrogel platform that maintains skin-compatible acidity, spreads with the right rheological feel, and retains antifungal function. The authors conclude that further studies involving additional microorganisms, appropriate control formulations, quantitative antimicrobial assays, and longer-term stability evaluation are needed to comprehensively assess the applicability and functional performance of the developed hydrogel system.

Subject of Research: Multi-component β-cyclodextrin inclusion complexes embedded in hydroxyethyl cellulose hydrogels for cosmetic delivery

Article Title: Preparation and application of functional hydroxyethyl cellulose hydrogels containing β-cyclodextrin complexes for cosmetic materials

Article References: Park, C.-H., Lee, S.-B., Kim, J.-T., Oh, S.-H., & Choi, S.-H. (2026). Preparation and application of functional hydroxyethyl cellulose hydrogels containing β-cyclodextrin complexes for cosmetic materials. Frontiers in Materials, 13, Article 1990804. https://doi.org/10.3389/fmats.2026.1990804

Image Credits: AI Generated

DOI: 10.3389/fmats.2026.1990804

Keywords: β-cyclodextrin, hydroxyethyl cellulose, hydrogel, inclusion complex, arbutin, niacinamide, benzoic acid, cosmetic formulation, antifungal activity, Candida albicans, rheology, co-delivery