Ethyl Lauroyl Arginate-Integrated Lipid Nanoparticles as a Multifunctional Non-Antibiotic Platform: Physicochemical Stability, Follicular Penetration, and Broad-Spectrum Activity Against Canine Skin Pathogens.

Background/Objectives: Canine superficial pyoderma is one of the most common dermatological diseases in dogs and is increasingly complicated by antimicrobial resistance. This study aimed to develop ethyl lauroyl arginate-integrated lipid-based nanoparticles (LAE-LBNs) as a non-antibiotic topical delivery platform and to evaluate their physicochemical stability, skin localization, and antimicrobial activity against clinically relevant canine skin pathogens. Methods: LAE-LBNs were prepared using high-shear homogenization followed by probe ultrasonication and characterized for particle size, polydispersity index, zeta potential, morphology, encapsulation efficiency, and storage stability. Antimicrobial activity was evaluated against methicillin-susceptible Staphylococcus pseudintermedius (MSSP), methicillin-resistant S. pseudintermedius (MRSP), and Malassezia pachydermatis. The ex vivo distribution of Nile Red-labeled formulations was assessed in porcine ear skin using fluorescence microscopy. Results: The optimized 5% LAE-LBN formulation exhibited a relatively small particle size, narrow size distribution, strongly positive surface charge (+46.49 mV), encapsulation efficiency exceeding 99%, and favorable physicochemical stability over two months. Fluorescence associated with the labeled LAE-LBN formulation was observed in the stratum corneum, viable epidermis, and hair follicles, whereas the aqueous control formulation was predominantly confined to the stratum corneum. LAE-LBNs exhibited bactericidal and fungicidal activity against MSSP, MRSP, and M. pachydermatis, with an MBC or MFC of 12.2 µg/mL. These endpoints were identical to those obtained for aqueous LAE, indicating that incorporation into the lipid-based nanocarrier preserved the antimicrobial activity of LAE. Conclusions: LAE-LBNs combined favorable physicochemical properties, follicular localization, and activity against bacterial and fungal canine skin pathogens. These findings support their further investigation as a non-antibiotic topical delivery platform for canine superficial pyoderma.