Shiseido Develops Next-Generation Microneedles That Deliver Overwhelming Skin Improvement Effects Safely And At Aesthetic Medicine Levels

Shiseido has developed next-generation microneedles*1 (Figure 1) having a unique structure*2 that achieve both safety and high efficacy aesthetic medicine quality effectiveness, and can be used daily. This is a new approach featuring two functions, ”injecting” and ”pressing,” allowing the injection of active ingredients into the superficial layer of the skin (the epidermis including the stratum corneum) without damaging the skin, while simultaneously providing stimulation via pressing force to the deeper parts of the skin (below the dermis). This leads to changes in the expression of gene clusters related to immunity, blood vessels, and the extracellular matrix*3 including collagen. It was revealed that these changes comprehensively activate the epidermis, dermis, and blood vessels and improve complex skin concerns such as sagging, barrier function, and wrinkles. With this technology, an ideal natural skin beauty can be easily and safely obtained as an extension of daily living. Going forward, Shiseido will continue to strive to create unprecedented new values and lifestyles. The results of this study were partly presented at the 34th IFSCC*4 Congress 2024 Brazil Iguazu Falls.

*1 Micro-scale ultra-fine needles. The use of microneedles has been promoted in the cosmetic and medical fields as a method to make tiny holes in the stratum corneum and thereby facilitate the intradermal delivery of drugs and cellular activation.
*2 Patent pending: WO2022071339A1, WO2023190584A1
*3 A complex insoluble macromolecule aggregate consisting of proteins and carbohydrates having a network structure in a gel-like form present in the intercellular spaces of living tissues.
*4 IFSCC: The International Federation of Societies of Cosmetic Chemists

Figure 1. Next-generation microneedles having a unique structure (for illustrative purpose)

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Next-generation microneedles equipped with mechanisms of not only ”puncturing” but also ”pressing” the skin, developed to solve conventional problems

In recent years, cosmetic medicine has become common as a way of realizing ideal skin, and there is a growing expectation for cosmetics to also be highly effective to that end. Microneedles, popularly used in cosmetic medical procedures, make tiny holes in the skin, which is regarded as helping increase the penetration of the active ingredients while also inducing a ”wound healing” reaction, allowing the structure deep inside the skin to rebuild and thereby produce high efficacy. On the other hand, there is also an invasive aspect such as bleeding caused by the procedure, so the burden and anxiety when undergoing the procedure have been issues. Shiseido therefore has come up with the idea of realizing simultaneously both high effectiveness and non-invasiveness, paradoxical factors, by adding the new function of ”pressing” to the conventional ”puncturing” function (Figure 2). Moreover, to solve problems such as limited types and amounts of active ingredients that can be loaded, the safety of the needle material, and the risk of the needles broken, a unique injection mechanism was developed. These new care approaches of ”injecting” and ”pressing” have been driving the company’s research forward, breaking away from conventional thinking.

Figure 2. Mechanism of action of next-generation microneedles (for illustrative purpose)

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New needle shape for achieving rapid active ingredient penetration

As a result of examining various shapes of microneedles, Shiseido identified shape parameters that allowed for precise penetration of only the superficial layers of the skin while efficiently providing pressure stimulation to the deeper layers, thereby developing a next-generation microneedle with an optimized shape. The microneedles developed through this research are capable of injecting active ingredients into the skin, and the results of evaluation of drug penetration revealed that there was a significant improvement in the amount of penetration of water-soluble drugs such as niacinamide, which were rapidly delivered to deeper parts of the skin (Figure 3).

Figure 3. Next-generation microneedles allow niacinamide to be delivered quickly to deeper parts of the skin

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Pressing alters the expression of gene clusters related to immunity, blood vessels, and the extracellular matrix, including collagen

The ”pressing” effect of next-generation microneedles has been shown to provide compressive stimulation to the deeper layers of the skin, instantly promoting blood flow. Additionally, using these microneedles every other day for seven days stimulates the deeper skin layers, leading to changes in the expression of gene clusters related to immunity, blood vessels, and the extracellular matrix including collagen. These results suggest that these microneedles have the potential for skin improvement without causing damage (Figure 4).

Figure 4. The pressing effect of next-generation microneedles comprehensively altered the expression of gene clusters in the deeper layers of the skin (dermis)

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Improvement in complex skin concerns such as sagging, barrier function, wrinkles, and transparency with niacinamide

Shiseido conducted a continuous use study of the next-generation microneedles with niacinamide. The results showed that wrinkles and transparency were improved in a shorter period compared to normal application. In addition, the evaluation of changes in the volume of the lower half of the face revealed a significant decrease in the lower face volume two weeks after the use of the next-generation microneedles (Figure 5). We also confirmed a significant improvement in sagging grade, and that after eight weeks, the nasolabial folds became shallower and shorter (Figure 6). More so, when we evaluated transepidermal water loss (TEWL), it became clear that the next-generation microneedles do not cause destruction of the barrier function, but rather improves it.

Figure 5. Next-generation microneedles significantly decreased the volume after two weeks
Figure 6. Next-generation microneedles changed the appearance of the nasolabial folds to be shallower and shorter after eight weeks

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