Propolis-Loaded Niosomes for Dermopharmaceutic and Cosmetic Applications: Development, Stability, Safety, and <i>In Vitro</i> Bioactivity Studies

Propolis, produced bybees, is composed of several biologically relevant phenolic compounds with known analgesic, anti-inflammatory, antitumor, antioxidant, immunomodulatory, wound healing, and antibacterial effects, having gained significant interest for therapeutic and cosmetic purposes. Niosomes, self-assembled vesicular nanosystems, are highly researched for topical delivery due to providing controlled and sustained release, protecting encapsulated compounds from degradation, improving stability, and having good biocompatibility and biodegradability. This work aimed to develop novel propolis-loaded niosomes with small and homogeneous particle size, high encapsulation efficiency, controlled release, adequate stability, relevant bioactivity, and high safety for topical application, for therapeutic and/or cosmetic purposes. Aided by quality by design (QbD) analysis, niosomes containing Tween 20, Kolliphor RH 40, cetyl alcohol, and/or cholesterol were produced by thin-film hydration followed by extrusion, with small particle size (between 100 and 200 nm), homogeneous distribution (PDI below 0.2), relevant ζ-potential (around -38 mV), good stability both under refrigeration and at room temperature, high encapsulation efficiency (ranging from 78.8 to 87.4%), and a controlled release profile, relevant to ensure prolonged bioactivity at the application site. Adequate concentration-dependent <i>in vitro</i> safety in keratinocytes and fibroblasts (up to 12.5 or 25 μg/mL) was demonstrated as well, with some niosomal formulations also showing a low irritative potential in a HET-CAM test, and relevant <i>in vitro</i> anti-inflammatory potential (IC₅₀ from 14.90 to 17.89 ng/mL). These novel nanoplatforms, containing a nature-derived hydrophobic compound with various relevant bioactivities, could serve as versatile and advantageous formulations in both pharmaceutical and cosmetic contexts of application.