Guangdong Laboratory for Lingnan Modern Agriculture, National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, PR China; Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics, Development and Safety Evaluation, South China Agricultural University, Guangzhou 510642, PR China.
Guangdong Laboratory for Lingnan Modern Agriculture, National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, PR China; Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics, Development and Safety Evaluation, South China Agricultural University, Guangzhou 510642, PR China; Jiangsu Co-Innovation Center for the Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou 225009, PR China.
J Control Release. 2022 Nov;351:896-906. doi: 10.1016/j.jconrel.2022.09.060. Epub 2022 Oct 11.
Targeted antibiotic delivery system would be an ideal solution for the treatment of enteropathogenic infections since it avoids the excessive usage of antibiotics clinically, which may lead to threat on public health and food safety. Salmonella spp. are Enteropathogens, but they are also robust HS producers in the intestinal tracts of hosts. To this end, the PEGylated poly (α lipoic acid) (PEG-PALA) copolymer nanoparticles with hydrophilic exterior and hydrophobic interior were designated in this study to encapsulate the antibiotics and release them in response to HS produced by Salmonella spp. The PEG-PALA nanoparticles demonstrated excellent stability in vitro and biocompatibility toward mammalian Caco-2 and 293 T cells. The release of ciprofloxacin from PEG-PALA nanoparticle was only 25.44 ± 0.57% and 26.98 ± 1.93% (w/w) in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) solutions without HS stimulation. However, the release amounts of ciprofloxacin were up to 73.68 ± 1.63% (w/w) in the presence of 1 mM NaS as HS source. In the mouse infection model, PEG-PALA nanoparticles encapsulated with ciprofloxacin (PEG-PALA@CIP) reduced the Salmonella colonization in the heart, liver, spleen, lung, cecum, and faeces, prolonged ciprofloxacin persistence in the intestine while reducing its absorption into the blood. More importantly, these nanoparticles reduced 3.4-fold of Enterobacteriaceae levels and increased 1.5-fold of the Lactobacillaceae levels compared with the drug administered in the free form. Moreover, these nanoparticles resulted in only minimal signs of intestinal tract inflammation. The HS-responsive antibiotic delivery systems reported in this study demonstrating a variety of advantages including protected the drug from deactivation by gastric and intestinal fluids, maintained a high concentration in the intestinal tract and maximally kept the gut microbiota homeostasis. As such, this targeted antibiotic delivery systems are for the encapsulation of antibiotics to target specific enteropathogens.
靶向抗生素递送系统将是治疗肠致病性感染的理想解决方案，因为它避免了临床上抗生素的过度使用，这可能会对公共健康和食品安全构成威胁。沙门氏菌属是肠致病性细菌，但它们也是宿主肠道中强有力的 HS 产生菌。为此，本研究设计了具有亲水外壳和疏水内核的聚乙二醇化聚（α-硫辛酸）（PEG-PALA）共聚物纳米粒子来包裹抗生素，并根据沙门氏菌属产生的 HS 来释放它们。PEG-PALA 纳米粒子在体外表现出优异的稳定性和对哺乳动物 Caco-2 和 293T 细胞的生物相容性。在没有 HS 刺激的情况下，环丙沙星从 PEG-PALA 纳米粒子中的释放量仅为 25.44±0.57%（w/w）和 26.98±1.93%（w/w）在模拟胃液（SGF）和模拟肠液（SIF）溶液中。然而，当存在 1mM NaS 作为 HS 源时，环丙沙星的释放量高达 73.68±1.63%（w/w）。在小鼠感染模型中，载有环丙沙星的 PEG-PALA 纳米粒子（PEG-PALA@CIP）减少了心脏、肝脏、脾脏、肺脏、盲肠和粪便中的沙门氏菌定植，延长了环丙沙星在肠道中的滞留时间，同时减少了其被吸收到血液中的量。更重要的是，与游离药物相比，这些纳米粒子降低了 3.4 倍的肠杆菌科水平，增加了 1.5 倍的乳杆菌科水平。此外，这些纳米粒子仅导致肠道炎症的最小迹象。本研究报道的 HS 响应性抗生素递送系统具有多种优势，包括保护药物免受胃和肠液的失活、维持肠道内的高浓度并最大限度地保持肠道微生物组的平衡。因此，这种靶向抗生素递送系统可用于封装抗生素以靶向特定的肠致病性细菌。
