RESUMO
Purpose: The topical application of antioxidants has been shown to augment the skin's innate antioxidant system and enhance photoprotection. A challenge of topical antioxidant formulation is stability and penetrability. The use of a targeted drug delivery system may improve the bioavailability and delivery of antioxidants. In this ex vivo study, we assessed the effects of the topical application of a liposome-encapsulated antioxidant complex versus a free antioxidant complex alone on skin photoaging parameters and penetrability in human skin explants. Patients and Methods: Human organotypic skin explant cultures (hOSEC) were irradiated to mimic photoaging. The encapsulated antioxidant complex and free antioxidant complex were applied topically onto the irradiated hOSEC daily for 7 days. The two control groups were healthy untreated hOSEC and irradiated hOSEC. Photoprotective efficacy was measured with pro-inflammatory cytokine (IL-6 and IL-8) and matrix metalloproteinase 9 (MMP-9) secretion. Cell viability and metabolic activity were measured via resazurin assay. Tissue damage was evaluated via lactate dehydrogenase (LDH) cytotoxicity assay. Skin penetration of the encapsulated antioxidant complex was assessed via fluorescent dye and confocal microscopy. Results: Compared to healthy skin, irradiated skin experienced increases in IL-6, IL-8 (p < 0.05), and MMP-9 (p < 0.05) secretion. After treatment with the encapsulated antioxidant complex, there was a 39.3% reduction in IL-6 secretion, 49.8% reduction in IL-8 (p < 0.05), and 38.5% reduction in MMP-9 (p < 0.05). After treatment with the free antioxidant complex, there were no significant differences in IL-6, IL-8, or MMP-9 secretion. Neither treatment group experienced significant LDH leakage or reductions in metabolic activity. Liposomes passed through the stratum corneum and into the epidermis. Conclusion: The topical application of a liposome-encapsulated antioxidant complex containing ectoin, astaxanthin-rich microalgae Haematococcus pluvialis extract, and THDA improves penetrability and restored IL-6, IL-8, and MMP-9 levels in irradiated human skin explants, which was not seen in the comparator free antioxidant complex group.
RESUMO
BACKGROUND: Tetrahexydecyl ascorbate (THDA) is a lipophilic precursor to ascorbic acid that may be stabilized by acetyl zingerone (AZ). Studies have shown that the topical application of THDA may have photoprotective effects. Similarly, AZ has been shown to mitigate oxidative and inflammatory stress, thereby improving the appearance of photoaging. AIMS: To examine the effects of THDA and AZ (THDA-AZ) on skin photoaging compared to THDA alone. PATIENTS/METHODS: In this double-blind, randomized controlled trial, healthy individuals aged 30 to 65 were included and 44 participants were randomized to receive either THDA-AZ (THDA 5% + AZ 1%) or THDA only (THDA 5%) for 8 weeks. Facial photographs were taken at 0, 4, and 8 weeks to analyze wrinkle severity, pigment intensity, and redness intensity. A skin colorimeter was used to assess infraorbital pigmentation and erythema. Self-perception of skin and tolerability were assessed through questionnaires. RESULTS: Average wrinkle severity was significantly decreased in the THDA-AZ group at Weeks 4 and 8 by 0.75% (p = 0.023) and 3.72% (p = 0.048), respectively, compared to the THDA group where wrinkle severity at Weeks 4 and 8 was increased by 7.88% and 4.48%, respectively. Facial pigment intensity was significantly decreased in the THDA-AZ group by 4.10% (p = 0.0002) at Week 8 compared to a 0.69% decrease in the THDA group. Facial redness intensity was decreased in the THDA-AZ group at Weeks 4 and 8 by 3.73% (p = 0.0162) and 14.25% (p = 0.045), respectively, compared to the THDA group where at Weeks 4 and 8 erythema increased by 27.5% and 8.34%, respectively. There were no significant differences in either group for infraorbital pigmentation or erythema. CONCLUSIONS: Daily use of combined THDA and AZ may improve facial wrinkle severity, pigment intensity, and erythema to a greater extent than THDA. While THDA alone increases facial wrinkle severity and erythema, the addition of AZ reduces both.
