Transdermal delivery of Acheta domesticus protein hydrolysate using nanostructured lipid carriers and Derma Stamp ― Does the combination of lipid-based formulation and a physical technique add value for permeation and retention?

Introduction

With over 1.3 million species, insects constitute the most abundant group of organisms on earth [1]. Thus, perhaps somewhat surprisingly, insects have only more recently emerged as valuable resources for human nutrition, medicinal applications, and as constituents in cosmetic products. Edible insects provide a valuable protein source, characterized by a beneficial amino acid profile alongside their protein abundance [2]. The house cricket (Acheta domesticus) is one of the edible insect species garnering specific attention as a novel protein and nutrient source, promising for the food industry as a safe and environmentally sustainable food option with significant biological value [3]. In addition to its role in the food industry, A. domesticus has also demonstrated appealing applications in the cosmetic and cosmeceutical areas. Our previous studies showed that extracts from A. domesticus demonstrate anti-skin aging properties, including stimulation of transforming growth factor-beta 1 (TGF-β1) expression, and inhibition of collagenase and hyaluronidase activities [4]. Additionally, bioactive peptides isolated from A. domesticus hydrolysate exhibit potent anti-skin aging effects, suggesting their potential as a cosmeceutical ingredient [5]. As protein hydrolysates have become increasingly popular as natural antioxidants due to their ability to release bioactive peptides containing 2–20 amino acid residues through hydrolysis [6], A. domesticus protein hydrolysates (PHs) offer a natural solution for anti-skin aging in cosmetic formulations. Nevertheless, a notable challenge persists due to the limited permeation of proteins and protein hydrolysates through the skin, affecting their effectiveness. The difficulty in delivering therapeutic proteins or protein hydrolysates through the skin arises from the natural impermeability of this biological barrier to large and polar molecules. Innovative delivery systems are thus essential to facilitate the efficient transportation of proteins and protein hydrolysates across the skin. Consequently, there has been a growing interest in the development of such delivery systems.

Among the various delivery systems, nanostructured lipid carriers (NLCs) have emerged as promising vehicles to enhance skin permeability and to target bioactive compounds in the skin layer [7]. Additionally, NLCs possess significant potential in both the pharmaceutical and cosmetics markets due to additional beneficial effects such as skin hydration enhancement [8]. NLCs were first developed in the late 1990s as substitutes for solid lipid nanoparticles (SLNs) to prevent cargo molecules from being expelled from the crystalline matrices formed by SLNs [9]. NLCs are structured with a core composed of a blend of solid and liquid lipids, where the solid lipids typically have longer chain lengths compared to the medium to short chains found in liquid lipids or oils [10]. This composition decreases the overall crystallinity of the nano-formulation compared to SLNs and introduces imperfections in the solid matrix, creating small environments for drug encapsulation [11]. As NLCs are known for their versatility in delivering both hydrophilic and lipophilic drugs [8], they may be a promising formulation option to effectively deliver protein hydrolysates derived from A. domesticus into and through the skin.

Transdermal permeation can also be enhanced through the application of physical techniques such as the use of ultrasound, iontophoresis, electroporation, magnetophoresis, and microneedles (MNs) [12]. The Derma Stamp, a device equipped with 140 medical-grade stainless steel needles of adjustable length [13], is a commercially available microneedling system. It perforates micron-sized channels through the stratum corneum, allowing both small and large molecules to reach the dermis without activating dermal nerves [14]. However, research comparing its effectiveness in skin permeation and retention, whether used alone or in combination with formulation methods such as lipid-based formulation, is scarce. To simplify the combination of physical techniques and formulations into a single application, dissolving MNs have become a focus of interest [15]. MNs act by perforating the stratum corneum and delivering proteins into the dermis through this minimally invasive route [16,17]. In the cosmetic industry, MNs have demonstrated effectiveness in creating precise channels for the penetration of cosmetic compounds and stimulating the wound repair process of the skin [18].

The present study aimed to compare skin permeation and retention of PH from either a simple aqueous solution or encapsulated into NLCs. In addition, the effect of applying physical techniques (Derma Stamp or MNs) on skin permeation and retention of PH was assessed, again from either a simple aqueous solution or encapsulated into NLCs. The study thus compared skin permeation and retention of PH from a simple aqueous solution and from an NLC formulation when combined with skin pretreatment using the Derma Stamp or a single application of dissolving MNs.

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Chemical reagents

Alcalase® enzyme from Bacillus licheniformis was purchased from EMD Millipore (Darmstadt, Germany). Dioctyl sulfosuccinate sodium salt (DSS), poly (vinyl alcohol) (PVA) (average molecular weight 85000–124000 g/mol), FluoroTag™ FITC conjugation kit, and polysorbate 80 (Tween® 80) were purchased from Merck KGaA (Darmstadt, Germany). Poly(1-vinyl-2-pyrrolidone) (PVP) K30 (molecular weight of 44000–54000 g/mol) and poloxamer (Kolliphor®) P188 were purchased from BASF (Florham Park, NJ, USA). Caprylic/capric acid triglyceride (Miglyol® 812 N) was a free sample from Cremer Oleo (Hamburg, Germany). Hydrochloric acid (HCl) and phosphate-buffered saline (PBS) tablets, containing 137 mM of sodium chloride (NaCl), 10 mM phosphate buffer, and 2.7 mM potassium chloride (KCl), were purchased from Thermo Fisher Scientific (Waltham, MA, USA). Glyceryl palmitostearate (Precirol® ATO 5) was obtained from Gattefossé (Lyon, France). All experiments utilized purified Milli-Q water obtained from a Milli-Q® Reference Ultrapure Water Purification System from EMD Millipore Corporation (Billerica, MA, USA).

Kankanit Yeerong, Grzegorz Sebastian Czyrski, Andrea Heinz, Anette Müllertz, Thomas Rades, Wantida Chaiyana,
Transdermal delivery of Acheta domesticus protein hydrolysate using nanostructured lipid carriers and Derma Stamp ― Does the combination of lipid-based formulation and a physical technique add value for permeation and retention?,
Journal of Drug Delivery Science and Technology, Volume 104, 2025, 106470, ISSN 1773-2247, https://doi.org/10.1016/j.jddst.2024.106470.

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