Xuanxuan Ma,Na Yang,Ruoyu Mao,Ya Hao,Da Teng,Yinhua Huang,Jianhua Wang
Antimicrobial peptides (AMPs) are antibiotic candidates; however, their instability and protease susceptibility limit clinical applications. In this study, the polylactic acid–glycolic acid (PLGA)–polyvinyl alcohol (PVA) drug delivery system was screened by orthogonal design using the double emulsion–solvent evaporation method. NZ2114 nanoparticles (NZ2114-NPs) displayed favorable physicochemical properties with a particle size of 178.11 ± 5.23 nm, polydispersity index (PDI) of 0.108 ± 0.10, ζ potential of 4.78 ± 0.67 mV, actual drug-loading rate of 4.07 ± 0.37%, encapsulation rate of 81.46 ± 7.42% and cumulative release rate of 67.75% (120 h) in PBS. The results showed that PLGA encapsulation increased HaCaT cell viability by 20%, peptide retention in 50% serum by 24.12%, and trypsin tolerance by 4.24-fold. Meanwhile, in vitro antimicrobial assays showed that NZ2114-NPs had high inhibitory activity againstStaphylococcus epidermidis(S. epidermidis) (4–8 μg/mL). Colony counting and confocal laser scanning microscopy (CLSM) confirmed that NZ2114-NPs were effective in reducing the biofilm thickness and bacterial population ofS. epidermidisG4 with a 99% bactericidal rate of persister bacteria, which was significantly better than that of free NZ2114. In conclusion, the results demonstrated that PLGA nanoparticles can be used as a reliable NZ2114 delivery system for the treatment of biofilm infections caused byS. epidermidis.
Na Yang,Yan Huang,Yuanyuan Li,Da Teng,Ruoyu Mao,Ya Hao,Lingyun Wei,Jianhua Wang
Staphylococcus pseudintermedius(S. pseudintermedius) is the main pathogen causing pyoderma of canines. With the emergence of drug-resistant bacteria, traditional antibiotic treatments are limited. As a potential antibacterial agent, NZ2114 was effective againstS. pseudintermedius, including drug-resistant strains. Its bactericidal efficacy was superior to mupiroxacin, ofloxacin and lincomycin. To facilitate the transcutaneous delivery of NZ2114 for the treatment of superficial pyoderma, chemical permeation enhancers were added since water-soluble NZ2114 does not easily penetrate the skin lipid layer. Two different NZ2114 sprays were prepared by combining 1% Azone + 10% propylene glycol (PG) or 5% N-methylpyrrolidone (NMP) + 10% PG with NZ2114 after screening. The cumulative permeability of NZ2114 sprays were 244.149 and 405.245 μg/cm2at 24 h with an in vitro percutaneous assay of mice skin, which showed a 244% and 405% increase in skin permeability than NZ2114, respectively. In addition, the efficacy of NZ2114 sprays in reducing skin bacteria colonisation was demonstrated in a mouse model of superficial pyoderma (24 mice, 3 mice/group) induced byS. pseudintermedius, and the 5% NMP + 10% PG + NZ2114 group had the best therapeutic effect compared to the other groups. This preparation did not cause any skin irritation, laying the foundation for the development of an effective and non-toxic topical product.Keywords:antimicrobial peptides;NZ2114;Staphylococcus pseudintermedius;transdermal delivery;chemical permeation enhancers;superficial pyoderma
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