Department of Thoracic Surgery, The First Affiliated Hospital of China Medical University, Shenyang, China.
Drug Deliv. 2021 Dec;28(1):2460-2468. doi: 10.1080/10717544.2021.2000676.
Bacteria-induced acute lung infection (ALI) is a severe burden to human health, which could cause acute respiratory distress syndrome (ARDS) and kill the patient rapidly. Therefore, it is of great significance to develop effective nanomedicine and therapeutic approach to eliminate the invading bacteria in the lung and manage ALI. In this study, we design a layer-by-layer (LbL) liposome-polymer hybrid nanoparticle (HNP) with a pH-triggered drug release profile to deliver antibiotics for the eradication of bacteria to treat ALI. The liposome is prepared by the lipid film hydration method with a homogenous hydrodynamic diameter and low polydispersity index (PDI). The antibiotic spectinomycin is efficiently loaded into the liposomal core through the pH-gradient method. The pH-sensitive polycationic polymer poly(-amino ester) (PBAE) and polyanionic sodium alginate (NaAIg) layers are decorated on the surface of liposome in sequence electrostatic interaction, resulting in spectinomycin-loaded layer-by-layer hybrid nanoparticles (denoted as Spe@HNPs) which have reasonable particle size, high stability, prolonged circulation time, and pH-triggered drug release profile. The results demonstrate that Spe@HNPs can efficiently induce the death of bacteria with low minimum inhibitory concentration (MIC) against () and drug-resistant MRSA BAA40 strains. The results reveal that Spe@HNPs can eradicate the invading MRSA BAA40 with improved antimicrobial efficacy and low side-effect for ALI treatment. This study not only reports a promising nanomedicine but also provides an effective method to prepare nanoplatforms for drug delivery and controlled release.
细菌诱导的急性肺感染（ALI）是人类健康的严重负担，可导致急性呼吸窘迫综合征（ARDS）并迅速导致患者死亡。因此，开发有效的纳米医学和治疗方法来消除肺部入侵的细菌并治疗 ALI 具有重要意义。在这项研究中，我们设计了一种具有 pH 触发药物释放特性的层层（LbL）脂质体-聚合物杂化纳米颗粒（HNP），以输送抗生素来消灭细菌，从而治疗 ALI。脂质体采用脂质膜水化法制备，具有均匀的水动力学直径和低多分散指数（PDI）。通过 pH 梯度法将抗生素大观霉素有效地装载到脂质体核心中。通过静电相互作用在脂质体表面依次修饰 pH 敏感的阳离子聚合物聚（-氨基酯）（PBAE）和阴离子多糖海藻酸钠（NaAIg）层，导致负载大观霉素的层层杂化纳米颗粒（命名为 Spe@HNPs）具有合理的粒径、高稳定性、延长的循环时间和 pH 触发的药物释放特性。结果表明，Spe@HNPs 可以有效地诱导具有低最小抑菌浓度（MIC）的细菌死亡，对（）和耐药性 MRSA BAA40 菌株有效。结果表明，Spe@HNPs 可以通过提高抗菌功效和降低 ALI 治疗的副作用来消除入侵的 MRSA BAA40。本研究不仅报道了一种有前途的纳米医学，还提供了一种用于药物输送和控制释放的纳米平台的有效制备方法。
