## 4 Discussion
studied the influence of applying various doses of quercetin of 0.03, 0.1, and 0.3% on wound contraction in rats. Quercetin dissolved in DMSO (75%) was applied topically once a day for 20 days to wounds; the control group received DMSO alone. The application of the natural flavonoid at a dose of 0.3% was shown to be more beneficial in accelerating cutaneous wound healing. During the first week of treatment, increased levels of proliferating PCNA-positive cells, decreased TNF-\(\alpha\) levels, and increased IL-10 expression were observed in the 0.3% quercetin-treated group compared to the 0.03%, 0.1% quercetin, and control groups, which, as a result, had a beneficial effect on the synthesis of collagen hydroxproline and pro-alpha I chain [78]. A test by [PERSON] and [PERSON] evaluated the influence of two solvents--propylene glycol and polyethylene glycol (PEG 400)--on the skin retention of quercetin. Propylene glycol was shown to be a more effective promoter of absorption than PEG 400. The amount of the flavonoid found in the skin was 1.47 times higher when propylene glycol was added to the semisolid base than PEG 400. No correlation was found between the kind of delivery systems used (gel, cream) and the dermal accumulation of quercetin [76]. In a study conducted on fresh Caucasian human skin, good penetration and retention of epigallocatechin-3-gallate and quercetin from green tea and G. biloba extracts contained in skin care preparations were found. The findings revealed that the flavonoids tested penetrated the skin while not reaching the receptor compartment. The highest amount of quercetin was determined in the viable epidermis (0.23 \(\mathrm{\SIUnitSymbolMicro g}\)/\(\mathrm{cm}^{2}\)) [79]. To study the penetration/retention of quercetin through porcine ear skin, [PERSON] et al. incorporated this natural flavonoid into hydroxypropyl methylcellulose (HPMC) or chitosan (CS) hydrogels. The retention of quercetin in the skin layers of chitosan hydrogels has been shown to be more than twice that of HPMC. After 8 h, flavonoid retention in pig ear skin was 0.57 \(\mathrm{\SIUnitSymbolMicro g}\)/\(\mathrm{cm}^{2}\) for HPMC and 1.42 \(\mathrm{\SIUnitSymbolMicro g}\)/\(\mathrm{cm}^{2}\) for CS. It was noted that when 5% \(\mathrm{\SIUnitSymbolMicro g}\)-CD was added to the hydrogels, API penetration/retention rose to 1.95 \(\mathrm{\SIUnitSymbolMicro g}\)/\(\mathrm{cm}^{2}\) for HPMC and 2.21 \(\mathrm{\SIUnitSymbolMicro g}\)/\(\mathrm{cm}^{2}\) for CS. The authors did not detect this flavonoid in the receptor fluid [61]. [PERSON] et al. investigated the antimicrobial efficacy of hydrogel membranes containing red propolis extract (RPE). The made hydrogels were based on 5% CMC and additionally with 0.5% and 1.0% citric acid. CMC was found to have a favorable effect on the release of phenolic compounds compared to the highly cross-linked 1% citric acid matrix. CMC with 0.5% citric acid as a membrane provided higher efficacy against _Staphylococcus aureus_ and _Staphylococcus epidermidis_ compared to the 1% citric acid cross-linked membrane. RPE-containing hydrogel membranes proved to be a stronger barrier to microorganisms that cause skin infections and can be used in the treatment of injured tissue [80].