## 12 Current Research Gaps, Future Directions, and Perspectives
Another strategy to align with the circular economy is developing stable enzyme formulations that maintain their activity over longer periods and are able to reduce the need for frequent repurchases, at the same time minimizing packaging waste. Advanced encapsulation techniques can shield enzymes from degradation, extending the shelf-life of cosmetic products. Also, proteolytic enzymes generate biodegradable, non-toxic waste (i.e., amino acids, peptides, and simple sugars), which does not accumulate in the environment, and offers a promising alternative to conventional chemical exfoliants, like microplastics, thereby reducing long-term pollution [22]. Future skincare products are likely to combine multiple proteolytic enzymes to harness their synergistic effects, pro viding enhanced exfoliation and further benefits like anti-inflammatory, antioxidant, and moisturizing properties [22]. Plus, a combination of proteolytic enzymes with antioxidants, peptides, and probiotics could enhance skin barrier function and hydration, as they could be integrated into hybrid products, like enzyme-infused moisturizers, serums, and masks, offering multifunctional skincare solutions, all in a single product [211]. Moreover, each enzyme's stability and activity may be optimized through pH, buffering, encapsulation, or pairing with stabilizers, as pH-responsive enzyme activation and time-release enzyme formulations may revolutionize skincare applications and offer adaptation to several skin types and conditions [92; 118; 163; 212]. Enzyme stability is one of the biggest challenges, since their effectiveness heavily depends on this. Future developments should additionally focus on delivery systems to enhance enzyme performance, extend their shelf-life, and optimize their activity during application. Nanotechnology enables the creation of advanced delivery systems that protect enzymes from degradation and enhance their skin penetration ability. Encapsulation methods, such as liposomes, microencapsulation, and polymeric nanoparticles, stabilize enzymes, regulate their release, and increase their cosmetic efficacy [57; 92; 118; 177; 175; 177; 212]. Regenerative skincare is another very promising area for proteolytic enzymes. Such enzymes are being explored for their potential in anti-aging applications, since they promote collagen production and aid in the acceleration cell turnover for a firmer, more youthful complexion with reduced wrinkles [213]. Additionally, the wound healing properties of certain proteolytic enzymes, like bromelain and papain, are harnessed in medical skincare therapies, aiming at repairing and rejuvenating damaged skin, concurrently preventing infections and healing wounds [147; 159; 161]. Proteolytic enzymes skincare is not still only limited to existing enzymes. Advances in biotechnology and bioinformatics are facilitating the discovery of novel enzymes from diverse natural sources, such as extreme environments including deep-sea vents and hot springs as well as unexplored plant species to identify enzymes with unique properties that are suitable for skincare products. CRISPR-Cas9 technology allows for modifications in enzyme genes and directed evolution could evolve enzymes with desired traits [214]. The future of proteolytic enzymes in cosmetics is bright, with emerging trends focusing on personalization, sustainability, multifunctionality, and advanced delivery. By integrating biotechnology, nanotechnology, and dermatological research, proteolytic enzymes are set to redefine skincare and offer solutions that are not only more effective, but also eco-friendly, gentle, and tailored to individual needs, meeting the evolving demands of consumers and cosmetic industries. However, more toxicological studies and long-term safety assessments, regulatory approval, and consumer education must be conducted to develop clear guidelines on enzyme-based exfoliation and skincare [17; 94; 163].