Topical delivery systems have garnered significant interests in dermatological therapeutics and cosmetic applications due to their non-invasive nature and ability to target localized areas effectively [[1], [2], [3]]. However, the strong barrier formed by the stratum corneum severely impedes the penetration of hydrophobic active ingredients, which is further compounded by their inherent instability and poor solubility in conventional formulations [4,5]. Emulsion-based carriers offer advantages in terms of drug loading capacity and formulation versatility [1]. Nevertheless, traditional emulsions stabilized by surfactants face critical limitations, including the potential for skin irritation, and environmental toxicity [6].

Pickering emulsions, stabilized by colloidal particles, have emerged as a promising alternative to traditional surfactant-based systems, demonstrating enhanced biocompatibility [7,8]. Although inorganic particles have been widely employed for stabilizing Pickering emulsions, growing consumer demands for natural and environmentally friendly ingredients have shifted research towards the development of naturally sourced particles as Pickering stabilizers [9,10]. Among various natural-based Pickering stabilizers, protein-types of particles have garnered significant attention as highly promising candidates due to their unique amphiphilicity, good biocompatibility and non-toxicity properties [11,12]. For example, soybean protein microgels have been developed to stabilize oil-in-water Pickering emulsions for lipid encapsulation [13]. Similarly, whey protein nanogels have been prepared to stabilize Pickering emulsion as a delivery system for curcumin, demonstrating remarkable stability and controlled release behavior [14]. Therefore, protein-types stabilizers represent a highly attractive and viable alternative to traditional surfactant in the development of advanced Pickering emulsion system.

Recently, numerous Pickering emulsions have been designed for topical delivery [15,16]. However, their potential is often constrained by relatively low delivery efficiency [17]. Many studies have found that carriers with a positive surface charge could effectively improve the delivery efficiency [[18], [19], [20], [21]]. For instance, Combrinck et al. utilized whey protein to synergistically stabilize emulsions with chitosan, and they observed that increasing the emulsion droplet charge enhanced electrostatic interactions between the emulsion droplets and negatively charged skin, thereby improving topical drug delivery [18]. Similarly, Sharkawy et al. developed a chitosan/collagen particle-stabilized Pickering emulsion for enhanced topical delivery of cannabidiol [21]. However, such positively charged particles often tend to lose colloidal integrity under high pH or high ionic strength conditions due to charge shielding effects. To date, few studies explored protein-based, positively charged Pickering emulsions for topical delivery that can maintain both good biocompatibility and strong stability across a range of environmental conditions.

To address these challenges, we propose creating positively charged composite protein colloidal particles by combining A-type gelatin (GT-A) with spirulina protein. Spirulina is a blue-green microalga with high protein content (60–70 wt%) and notable bioactivities, including moisturizing, antioxidation, antiaging, antimicrobial, and immunostimulant effects [22,23]. Its proteins exhibit strong emulsifying and hydrogel-forming properties, making it one of the most studied algal proteins [24]. However, previous work showed that spirulina protein stabilized-emulsions tend to coalesce near its isoelectric point (pH ≈ 3) [23]. GT-A not only has strong emulsifying capabilities but also carries a positive surface charge at neutral pH, with an isoelectric point around around pH 8, which performs well under acidic conditions [25,26]. Therefore, incorporating GT-A can address the acid-condition instability of spirulina protein-stabilized emulsions and promote stability over a broad pH range. Moreover, the positive charge of GT-A under neutral conditions enables the formation of surface-positively charged colloids through simple electrostatic interactions by tuning the spirulina protein-to-gelatin ratio.

Herein, spirulina protein isolate/gelatin (SG) composite particles was constructed to stabilize oil-in-water Pickering emulsion for topical delivery of hydrophobic active ingredients. Initially, the SG composite particles were formed through self-assembly driven by electrostatic interactions and hydrogen bonding. Subsequently, the emulsifying capacity of these composite particles was evaluated. The droplet size and stability of the resulting emulsion were characterized under various environmental conditions. Finally, α-Bisabolol (ABS) was encapsulated as a model active ingredient within the Pickering emulsions. The stability and delivery performance of ABS-loaded Pickering emulsions at varying loading amount were examined, and the underlying delivery mechanisms were investigated to elucidate their effectiveness for topical delivery.