The human skin is initial defense against environmental stressors such as ultraviolet (UV) radiation, pollutants, and pathogens. Prolonged exposure to these hazardous chemicals can engender reactive oxygen species (ROS), that leads to malignant transformations and cellular damage [1]. Furthermore, ROS disrupts the normal dermal enzymatic activity of elastase, hyaluronidase, collagenase, and tyrosinase, resulting in extrinsic skin aging, compromised skin integrity, and hyperpigmentation [2]. Previous studies revealed, that by causing loss of integrity, and strength in the skin, oxidative stress can trigger an ample spectrum of cellular deterioration, including DNA damage, inflammation, and lipid peroxidation that can lead to skin cancer [3]. This ultimately poses physical and psychological pressure to society. Dermatological scientists are on a continuous quest to address the detrimental effects of environmental stressors but the investigative treatments often fail to address these multiple skin ailments [4]. Hence, combination products are needed as they can target multiple pathways by which oxidative stress-induced skin damage progresses.

Interestingly, plant-derived phytochemicals have potent antioxidant activity and a safe nature that makes them capable of grafting into personal care formulations. In preventing and treating dermatological issues, flavonoids' radical scavenging properties are crucial [5]. Rutin also referred to as quercetin-3-rutinoside or sophorin, is a flavonol glycoside that is composed of the disaccharide rutinose and the flavonol quercetin. It possesses substantial scavenging properties against oxidizing species, including the superoxide radical, hydroxyl radical and peroxyl radical. Rutin provides an advantage over quercetagenin, myricetin, and other flavonoids [28]. however, it was emphasized that the utility of flavonoids in skin delivery is limited by short half-life, and low stability, which can sometimes oppose their eminence [6].

Mesoporous silica nanoparticles (MSNs) were proven to be “odds-on-favorite” nano-carriers. As reported earlier, NH2-MCM-41 played a major role in stabilizing rutin against UV degradation. It performed better when immobilized in aminopropyl silica in terms of photostability and activity, indicating the significance of functionalization in maintaining organic compounds within silica mesopores [7]. Similarly, Ugazio et al. verified that the antioxidant activity of flavonoids can be accentuated following confinement in silica nanoparticles [8]. Notably, another imperative topical agent, zinc oxide, an inorganic substance with a wide range of functions, can satisfy the demand for combination products [9]. Zinc oxide has been used in sunscreens and other active topical products for decades. As reported earlier, the ZnO, in combination with titanium dioxide (TiO2), provided an admirable sun protection factor (up to 93 %) [10]. Similarly, Wikantyasning et al. formulated a cream having ZnO and spirulina as active ingredients and found that both synergistically enhanced the antioxidant activity (IC50 = 276.92 ± 23.85 μg/mL) [11].

Based on relevant literature, these two active ingredients were considered promising agents to embark on multiple skin complications. This research is an exploitation of a nano-flavonoid and a metallic oxide fabricated gel as a potent skin rejuvenation tool, in a single novel gel. Carbopol 940 was used as a topical gelling agent, it has been extensively used in research due to its non-toxic profile [12]. Conversely, due to the complex chemical nature of zinc oxide and its poor aqueous solubility, xanthan gum was chosen as a stabilizer. It is reported to create a three-dimensional network in aqueous systems that prevent the sedimentation and phase separation. The negatively charged glucuronic acid of xanthan gum residues interact electrostatically that inhibits the aggregation and ensures uniform dispersion of poorly soluble compounds [13]. One of the previous studies also suggested that xanthan gum is beneficial for its stable network in carbopol, as previously utilized in divergent formulations [14]. Alternatively, gums are a promising type of biopolymer, as they are readily accessible, renewable, affordable, non-toxic, stable, hydrophilic, biocompatible, and biodegradable. Its promising and anticipated effects against skin cancer were evaluated in vitro and anti-aging and anti-melanogenesis parameters were examined by in vivo placebo-controlled, split-faced study of human volunteers. This work epitomizes a significant step towards developing and evaluating a clinically sustainable formulation for various dermatological applications, including photoaging, hyperpigmentation, and ROS-induced skin cancer.