Botanical and Upcycled Bioactives for Advanced Topical Formulations: Mechanistic Pathways, Cutaneous Delivery, and...

Natural and sustainable cosmetics represent a rapidly evolving frontier in dermatological science, integrating plant-derived bioactive compounds with advanced delivery technologies and environmentally conscious formulation design. Botanical ingredients, including polyphenols, flavonoids, terpenoids, alkaloids, and polysaccharides, modulate key biological pathways involved in oxidative stress, inflammation, extracellular matrix remodeling, pigmentation, and immune responses, thereby supporting skin regeneration, protection, and homeostasis. To overcome limitations related to instability, compositional variability, and limited skin penetration, these compounds are increasingly incorporated into advanced delivery systems such as nanoemulsions, solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), vesicular systems, microneedle platforms, three-dimensional matrices, and plant-derived extracellular vesicles (PDEVs). These technologies enhance cutaneous bioavailability, enable controlled release, and improve tissue targeting, linking formulation design to exposure-response relationships. In parallel, sustainability has become a critical component of product development. Circular economy strategies, including the upcycling of agro-industrial by-products, green extraction technologies, biodegradable packaging, and life cycle assessment, are reshaping cosmetic innovation. Regulatory frameworks are also evolving to address safety, efficacy, and transparency of natural claims, as well as the challenges of botanical standardization. This narrative review, conducted through a structured literature search, provides a mechanistically oriented analysis of botanical ingredients in dermatology, emphasizing molecular pathways, skin delivery science, and safety considerations. Rather than cataloguing ingredients, it proposes a translational framework linking phytochemistry, delivery science, safety-by-design principles, and sustainability to support the rational development of effective and safe dermatological formulations.