UNISOUL® RNAiW
UNILIPO Patent Pending Ingredient
Invention Patent Application Number: 202310212074.0
Invention Name: A siRNA Molecule for Inhibiting Melanin and Its Application
Invention Patent Application Number: 202310564266.8
Invention Name: Preparation Method and Application of a siRNA Supramolecular Microcapsule with Whitening Effect
Small interfering RNA (siRNA) technology holds significant importance in addressing challenging diseases and future drug development. Its unparalleled precision in gene intervention, high treatment efficacy, and the ability to target multiple genes suggest that gene interference techniques will become increasingly vital in the coming decades.
In a nutshell, the mechanism of siRNA involves specifically targeting and silencing or "switching off" a particular gene to achieve desired effects.
This mechanism is particularly relevant in skincare, especially in whitening. Traditionally, our focus on whitening has mostly centered around melanin synthesis and metabolic pathways associated with tyrosinase enzymes. The most common enzymes in this context include tyrosinase (TYR), tyrosinase-related protein 1 (TRP-1), and tyrosinase-related protein 2 (TRP-2), among others, as depicted on the left side of the diagram below.
The most common whitening ingredients such as 377 derivatives, kojic acid, arbutin, glabridin, etc., all exert their whitening effects through the melanin synthesis pathway.
However, the mechanism of UV-induced tanning and the formation of pigmentation such as melasma are rarely discussed, which involves upstream signaling pathways for tanning.
UV radiation or skin inflammation can lead to DNA damage and activation of p53, subsequently activating the formation of α-MSH. α-MSH binds to the MC1R receptor on melanocytes, leading to an increase in cAMP and activation of PKA.
Activation of protein kinase A directly leads to increased expression of a key gene—MITF. Speaking of MITF, it's quite interesting.
Unlike the well-known tyrosinase gene, MITF is relatively understated, yet it plays a crucial role.
The MITF gene is not only closely related to the development of melanocytes, retinal pigment epithelial cells, and mast cells, but it also regulates several key enzymes involved in melanin synthesis, including tyrosinase (TYR), tyrosinase-related protein 1 (TRP-1), and tyrosinase-related protein 2 (TRP-2), among others.
In summary, MITF is the most critical regulatory gene for melanocytes during development and the primary gene regulating melanin synthesis.
Since MITF is upstream of tyrosinase, reducing MITF expression can effectively halt melanin synthesis, thus preventing pigment deposition and various pigmentation issues (especially sunspots and melasma) caused by UV radiation or inflammation.
Therefore, it can be understood that while downstream melanin synthesis pathways involving tyrosinase determine skin color, the upstream tanning pathway mediated by MITF is crucial for rapid pigmentation removal.
I have simplified the diagram from the literature mentioned above to aid understanding.
Especially in recent years, in clinical trials and experiments, silencing the expression of MITF has proven effective in treating various pigmentation issues, including melasma. A 12-week clinical study demonstrated that inhibiting the expression of MITF showed better results in removing melasma compared to using 10% MAP (Magnesium Ascorbyl Phosphate)
Based on the genetic sequence of MITF, we have designed a specific Small interfering RNA (siRNA) sequence capable of inhibiting its mRNA expression, which forms the core genetic sequence within UNISOUL® RNAiW. We have selected the thiol-modified phosphorothioate modification from various chemical groups, as it exhibits the highest efficiency in silencing MITF.
However, the major drawback of siRNA is its poor transdermal absorption due to carrying a large number of charges. Therefore, we have developed specially formulated supramolecular liposomes for encapsulation.
Compared to traditional liposome encapsulation, the supramolecular technique enhances the transdermal absorption efficiency of siRNA. This improvement is evident from skin confocal laser scanning microscopy experiments conducted at 4 hours and 16 hours post-application.
（To monitor the penetration efficiency and depth of siRNA in the skin, we utilize green fluorescent labeling）
With the powerful support of our supramolecular liposome encapsulation, our UNISOUL® RNAiW exerts strong inhibitory effects on key genes.
Firstly, we evaluate the inhibition of various key enzymes involved in melanin synthesis. Regardless of whether at the mRNA transcription level or protein expression level, the four most critical genes—MITF, TYR, TRP-1, and TRP-2—exhibit significant inhibition.
Left: Effect of siRNA on transcriptional silencing of the MITF gene.
Right: Silencing of several key genes in the melanin synthesis pathway by siRNA. Thicker bands indicate higher expression, while thinner bands indicate lower expression, demonstrating effectiveness.
Compared to the gold standard whitening agent KOJIC ACID, UNISOUL® RNAiW evidently exhibits a more explosive melanin inhibition capability.
Using 0.8% UNISOUL® RNAiW results in a 64.7% lower melanin content compared to KOJIC ACID. And this is just at a concentration of 0.8%; it's worth noting that UNILIPO Pterostilbene Serum contains a concentration of 5%.
In clinical trials for depigmentation conducted on human subjects, the results are equally promising. After using 5% UNISOUL® RNAiW for 14 and 28 days, there were improvements observed in the quantity and size of brown spots and UV-induced pigmentation.
Statistical data indicates that using UNISOUL® RNAiW raw material alone for 28 days can significantly reduce skin melanin by 2.44% and substantially enhance skin brightness by 1.53%.
Adding all three patented whitening active ingredients results in UNILIPO Pterostilbene Serum.
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