The liposome-based dermatocosmetic formulations have the compositions presented in
Table 1, briefly: xanthan gum 0.5%, propylene glycol 8%,
Calendula officinalis oil 5.0%,
Argania spinosa oil 5%,
Helianthus annuus oil 5%, liposomes with hydroalcoholic extract of red/white grape pomace 2%, vitamin E 0.5%, cetearyl alcohol 3%, olive oil-based emulsifier 6%, and purified water up to 100%. The natural ingredients, namely red/white grape pomace extracts,
Calendula officinalis,
Argania spinosa, and
Helianthus annuus oils, xanthan gum, and olive oil-based vegetable emulsifier, promote the current concept of “green cosmetics”. Using liposomes to deliver bioactive substances from hydroalcoholic extracts results in the active principles being progressively released into the skin. In this regard, this research aimed to develop liposomal formulations that would hydrate the skin, improve its appearance, reduce wrinkles, and provide anti-ageing, antimicrobial, anti-inflammatory, and potentially protective effects against UVA and UVB radiation.
3.1. Characterization of Liposomes Encapsulated Red and White Grape Pomace Extracts
Liposomal encapsulation protects polyphenolic compounds from environmental degradation by shielding them from oxidation and exposure to light. Additionally, liposomes can enhance skin penetration and deliver active ingredients over an extended period, ultimately improving the formulation’s biological efficacy. The thin-film hydration technique, followed by sonication and extrusion, is an easy, consistent, and widely applicable method for preparing liposomes, offering good control over size, versatility in encapsulation, and compatibility with a wide range of bioactive extracts.
The entrapment efficiency of liposomes loaded with local red and white grape pomace extracts (coded L@ND, L@FA, L@FN, and L@TR) ranged from 65.62 ± 0.06% to 60.12 ± 0.05% (
Table 2). The variation in EE could be linked to the physicochemical properties of the extracts (e.g., polarity, molecular weight), which influence interaction with the lipid bilayer during hydration. The mean particle sizes of the liposomal formulations ranged from 166.3 nm to 184.2 nm, indicating the formation of nanometric vesicles suitable for dermatocosmetic applications.
The polydispersity index (PDI) values ranged from 0.301 to 0.350, indicating a moderately narrow size distribution and good overall homogeneity among the liposome populations (
Table 2). All samples presented PDI values below 0.4, which is typically acceptable for stable colloidal systems intended for topical use. PDI is used as an indicator of the extent of the molecular weight distribution. Similar results were previously reported. For example, Montagner et al. (2022) [
38] reported grape seed extract liposomes via the reverse-phase evaporation method with a 239 nm and PDI of 0.252, and Rached et al. (2025) [
39] prepared liposomes containing a Lebanese grape variety via hydration combined with sonication with a size of 148 nm and a PDI value below 0.3.
Therefore, liposomes exhibited appropriate nanoscale dimensions, good homogeneity, and satisfactory encapsulation efficiencies, indicating that all formulations are well-suited for incorporation into dermatocosmetic creams, ensuring effective delivery and stability of the pomace-derived actives.
3.2. Characteristics of Dermatocosmetic Formulation
Red and white grape pomace extracts from the local Fetească Neagră and Negru de Drăgășani varieties, and Fetească Albă and Tămâioasă Românească varieties, respectively, are embedded in liposomes and harmonized with a series of natural essential oils, such as
Calendula officinalis,
Argania spinosa, and
Helianthus annuus, xanthan gum, Olliva emulsifier, and vitamin E. These ingredients form a creamy, odourless, pearly white-yellow dermatocosmetic formulation (
Table 3). Additionally, a Cream-base was prepared as a reference formulation. Cream-base consists of the same excipients (xanthan gum, Olliva emulsifier, and vitamin E) but lacks liposomes or white grape pomace extracts liposome, serving to highlight the impact of the extracts on the cream’s physical, sensory, and functional properties.
Thus, the dermatocosmetic creams enriched with liposomes (i.e., Cream-L@ND, Cream-L@FA, Cream-L@FN, Cream-L@TR) demonstrated consistent physical and sensory characteristics. Organoleptic evaluations after 60 days at 4–8 °C of storage confirmed the stability of all formulations, with each cream maintaining a homogeneous, pearl-yellowish-white appearance, odourless profile, and no signs of phase separation, sedimentation, or texture degradation. The pH values remained within a physiologically acceptable dermal range (5.01–5.37), showing only minimal fluctuations over time, indicating the formulations’ chemical stability (
Table 3). Cream-base exhibited similar organoleptic stability, maintaining homogeneity and odourless appearance after 24 h, with pH 5.25 ± 0.01, slightly higher than the liposome-enriched creams but still within the acceptable dermal range (
Table 4). The slightly higher pH may be attributed to the absence of acidic phenolic compounds from grape pomace extracts, which can lower the pH of enriched formulations, as previously reported in cosmetic creams enriched with grape stem extracts [
9]. This confirms that the base formulation itself is stable and compatible with skin pH.
The texture analysis profile (TPA) of dermatocosmetic creams is a critical parameter that reflects the mechanical and sensory properties of a formulation, directly influencing its consumer acceptance, stability, and performance on the skin. Parameters such as firmness, cohesiveness, and springiness provide quantitative insights into the product’s structure, spreadability, and resilience during application. At 24 h, Cream-L@FA exhibited the highest firmness (0.500 N), followed closely by Cream-L@TR and Cream-L@ND, whereas Cream-L@FN showed the lowest value (0.394 N). The Cream-base exhibited lower firmness (0.378 N) than the liposome-enriched formulations, highlighting the reinforcing impact of both liposome incorporation [
40] and bioactive grape extracts on the structural integrity of the creams, as previously observed in grape-extract-enriched cosmetic formulations [
9]. Cohesiveness and springiness displayed similar patterns, with Cream-L@FN presenting the greatest cohesiveness (0.598) and Cream-L@FA the highest springiness (0.997), indicating enhanced structural recovery and elasticity in these formulations (
Table 4 and
Table 5). By comparison, Cream-base cohesiveness (0.572) and springiness (0.820) were slightly lower, suggesting that the presence of liposome-loaded pomace extracts enhances the overall structural strength and elasticity of the matrix, in agreement with previous reports on nanomaterial- and grape-extract-enriched cosmetic formulations [
9,
40]. After 30 days, all samples demonstrated an overall increase in TPA parameters, particularly firmness, with Cream-L@FA and Cream-L@ND reaching 0.801 N and 0.753 N, respectively (
Table 4 and
Table 5). Although Cream-base data after 30 days were not measured, its lower initial firmness suggests that matrix strengthening would be less pronounced without active extracts.
This behaviour suggests a progressive strengthening of the formulation matrix, likely resulting from polymeric interactions (e.g., xanthan gum cross-linking) or internal structural rearrangements during storage. Cohesiveness values became more uniform among formulations at this stage, stabilizing between 0.46 and 0.50, while springiness exhibited a slight overall decline. After 60 days, a moderate decrease in firmness was observed in most formulations compared to 30 days, with values ranging from 0.629 N (Cream-L@FN) to 0.729 N (Cream-L@ND), suggesting minor structural relaxation or reorganization within the emulsion network over time (
Table 4). Despite this reduction, the creams maintained relatively consistent firmness, reflecting good physical stability throughout storage. Cohesiveness continued to decrease slightly, particularly in Cream-L@ND and Cream-L@FA, likely due to gradual water loss; however, Cream-L@FN maintained the highest cohesiveness (0.538), demonstrating superior internal structuring. Springiness remained relatively stable or even increased in certain formulations, particularly Cream-L@ND (1.012) and Cream-L@FN (1.042), indicating sustained elastic recovery and satisfactory spreadability after deformation.
Collectively, these findings confirm that all liposome-enriched creams retained acceptable textural characteristics after 60 days, with minimal deterioration in mechanical performance and good overall structural stability. These results suggest that while the creams retained their integrity, their internal matrix matured, becoming firmer but maintaining acceptable levels of elasticity and cohesiveness.
The spreadability test provides valuable insight into the ease of application of dermatocosmetic creams, a key factor in user comfort and product performance (
Table 6).
Using the Ojeda–Arboussa method, the creams demonstrated a high degree of spreadability. These properties highlight the potential of these formulations for safe, effective, and consumer-acceptable cosmetic applications.
For all four liposome-based creams, the spreading surface area increases steadily as the amount applied increases (
Table 6). This is typical behaviour for semi-solid products: the greater the amount applied, the thicker the film formed and the greater the surface area covered. The increases are approximately linear, but differ in amplitude between products. Cream-L@TR shows the highest spreading capacity. Over the entire range of measurements, Cream-L@TR consistently exceeds the other creams, with spreading surfaces of 2206 mm
2 at 125 g and 5674 mm
2 at 875 g. At the opposite pole, Cream-L@FN shows the lowest spreading capacity. Cream-L@FN has the smallest surface area of all the products when measured on almost all levels, with surface areas of 1963 mm
2 at 125 g and 4071 mm
2 at 875 g. Cream-base also demonstrated high spreadability, comparable to Cream-L@TR, indicating that the base formulation allows for efficient application and uniform film formation even in the absence of bioactive extracts. This behaviour can be attributed to the rheological properties of the excipients in the base, such as xanthan gum and Olliva emulsifier, which provide sufficient structural integrity while maintaining low resistance to flow under applied stress. The absence of densely loaded liposomes or particulate bioactives reduces internal resistance, facilitating deformation and spreading. Moreover, the semi-solid nature of the emulsion imparts shear-thinning behaviour, allowing the cream to spread easily during application. These observations are consistent with previous reports on nanomaterial- and extract-enriched cosmetic formulations, where excipient composition and matrix flexibility have a significant influence on spreadability [
9,
40,
41].
The antioxidant activity of the samples was quantified using the DPPH radical scavenging assay and expressed as inhibition percentage and Trolox equivalents. All creams exhibit high inhibition percentage (>91%), indicating strong antioxidant activity. The values range narrowly from 1.725 to 1.777 mM/g, suggesting that all formulations have similar antioxidant capacities (
Table 6). These results indicate the preservation of bioactive compounds post-formulation.
In terms of percentage inhibition, Cream-L@ND exhibited the highest antioxidant activity (93.79 ± 0.94%), with Cream-L@FN following closely behind (93.51 ± 0.94%). These values are almost identical, suggesting that the two formulas contain similar amounts of active compounds or ingredients with strong antioxidant properties. Cream-L@TR (91.72 ± 0.92%) and Cream-L@FA (91.08 ± 0.91%) recorded slightly lower values, but both still fall into the category of products with intense antioxidant activity (
Table 7).
The results obtained are also supported by the determinations expressed in Trolox equivalents (TEAC), where the same order of antioxidant efficiency is observed. Cream-L@ND (1.777 ± 0.018 mM/g) and Cream-L@FN (1.772 ± 0.018 mM/g) have the highest values for equivalent antioxidant capacity, confirming the consistency of the data on radical inhibition. Cream-L@TR (1.737 ± 0.017 mM/g) and Cream-L@FA (1.725 ± 0.017 mM/g) have lower values that are still close, indicating comparable antioxidant activity that is slightly lower than that of the first two samples.
The Cream-base showed only modest activity (~11.36% inhibition), attributable to the minor antioxidant contribution from vitamin E and oils (Calendula officinalis oil, Argania spinosa oil, Helianthus annuus oil) in the excipient blend. Despite these baseline effects from the excipients, the 8- to 9-fold higher activity in the liposome-loaded creams clearly demonstrates that the predominant radical scavenging originates from the encapsulated grape pomace extracts (rich in phenolics like resveratrol, catechins, and proanthocyanidins) delivered via liposomes, rather than the other formulation components.
These findings align with the well-established radical-scavenging mechanisms of polyphenols and flavonoids, the major bioactive constituents of grape pomace extracts. These compounds exhibit antioxidant activity primarily through the donation of electrons or hydrogen atoms, which stabilizes reactive oxygen species (ROS) such as superoxide anions, hydroxyl radicals, and peroxyl radicals. By neutralizing these reactive species, polyphenols and flavonoids prevent oxidative damage to cellular lipids, proteins, and nucleic acids, thereby maintaining the structural and functional integrity of skin cells [
42,
43].
In addition to direct radical scavenging, polyphenols can chelate transition metal ions (e.g., Fe
2+, Cu
2+), which catalyze the formation of highly reactive radicals via Fenton-type reactions, reducing oxidative stress [
44,
45,
46]. They may also modulate endogenous antioxidant defence systems by upregulating enzymes such as superoxide dismutase (SOD), catalase, and glutathione peroxidase, enhancing the skin’s intrinsic capacity to counteract oxidative damage [
47,
48].
The radical-scavenging effects of grape polyphenols can be conceptually compared to those of classical antioxidants such as vitamins C and E. Vitamin C primarily acts in the aqueous compartments of cells by donating electrons to neutralize free radicals, whereas vitamin E is lipid-soluble and protects cell membranes by intercepting lipid peroxyl radicals [
49].
Polyphenols, depending on their structure, can act in both hydrophilic and lipophilic environments, allowing versatile protection across cellular compartments.
Encapsulation in liposomes enhances the antioxidant potential of grape pomace extracts by improving the stability and bioavailability of polyphenols and flavonoids. Liposomal encapsulation protects these compounds from degradation caused by environmental factors such as light, oxygen, and pH changes, while promoting deeper skin penetration. This targeted delivery ensures that bioactive molecules reach the dermal layers where oxidative stress is most pronounced, optimizing radical-scavenging and protective effects [
50,
51].
In general, the tested formulations demonstrate robust potential to counteract oxidative stress at the skin level. The higher concentrations of Trolox equivalents in Cream-L@ND and Cream-L@FN may indicate a greater amount of antioxidant ingredients or stronger synergy between the compounds in these formulations.
In conclusion, the analysis demonstrates that all evaluated dermatocosmetic creams exhibit strong antioxidant activity, with slight superiority observed in Cream-L@ND and Cream-L@FN. These results confirm the products’ potential to protect the skin against oxidative damage and support their use in formulations aimed at maintaining skin health and a youthful appearance.
3.3. Release Patterns of Polyphenols from Dermatocosmetic Creams
The four cream formulations (i.e., Cream-L@ND, Cream-L@FA, Cream-L@FN, and Cream-L@TR) exhibited a slow cumulative release of polyphenolic compounds. By 96 h, all formulations had approached their plateau values, with Cream-L@FA and Cream-L@TR achieving near-complete release (over 97%) and Cream-L@ND and Cream-L@FN reaching 91–92%. After 120 h, the cumulative release exceeded 95% for all samples. Overall, the data suggest that liposomal encapsulation within cream matrices can provide controlled, prolonged release of bioactive polyphenols.
It is evident that the Cream-L@TR and Cream-L@FN formulations have a faster onset and reach the plateau stage more quickly. In contrast, Cream-L@ND and Cream-L@FA have a slower release rate, although they also reach >95% at 120 h (
Table 8 and
Figure 1). The prolonged-release profiles of all formulas suggest the efficiency of liposomal encapsulation in controlling the release of polyphenols.
The release kinetics of polyphenols from proposed cream formulations were evaluated by fitting several mathematical models, including zero-order, first-order, Korsmeyer–Peppas, and Hixson–Crowell models, to identify the most accurate description of the release mechanism. Kinetic analyses were performed using KinetDS 3 software. The equations applied were as follows.
Hixson–Crowell model:
where
—amount of polyphenols released at time
t;
—zero-order rate constant of the drug release rate;
k—first-order rate constant;
—rate constant of the Higuchi model;
—Korsmeyer–Peppas release rate constant;
n—exponential factor;
KHC—Hixson–Crowell release rate constant.
The most appropriate kinetic model was determined based on the correlation coefficient (R2), root mean square error (RMSE), and Akaike information criterion (AIC). A suitable model was considered one that demonstrated an R2 value close to 1.0, along with low RMSE and AIC values, indicating accurate and reliable prediction of polyphenol release behaviour.
Table 9 shows R
2, RMSE, and AIC values for the fitting models. The polyphenol release profiles from dermatocosmetic products were best described by the Korsmeyer–Peppas model for all formulations. This is evidenced by the highest correlation coefficients (R
2) and the lowest RMSE and AIC values compared to the other models. Specifically, creams containing liposomes loaded with red and white grape pomace extract showed R
2 values of 0.953, 0.921, 0.955, and 0.926, respectively, indicating a strong fit to the Korsmeyer–Peppas equation. In contrast, the zero-order and Hixson–Crowell models showed moderate correlation (R
2 ranging from 0.575 to 0.831) with higher RMSE and AIC values, and the first-order model exhibited the poorest fit (R
2 between 0.490 and 0.562).
Table 10 presents the Korsmeyer–Peppas release mechanism parameters and highlights that all formulations had the exponent values (n) below 0.5, suggesting Fickian diffusion as the primary release mechanism.
Based on the K
p values (
Table 10 and
Figure 2), the Cream-L@TR and Cream-L@FN formulations release the active ingredient faster than the Cream-L@ND and Cream-L@FA formulations. All creams demonstrate a Fickian diffusive release mechanism (n < 0.5). The differences in K
p values demonstrate the effect of composition on release rate, despite the mechanism remaining the same.