Amrita Centre for Nanosciences and Molecular Medicine, Amrita Institute of Medical Sciences and Research Centre, Amrita Vishwa Vidyapeetham, Amrita University , Kochi 682041, India.
ACS Appl Mater Interfaces. 2016 Aug 31;8(34):22074-83. doi: 10.1021/acsami.6b07463. Epub 2016 Aug 19.
Compared to the current treatment modalities, the use of an injectable hydrogel system, loaded with antibiotic encapsulated nanoparticles for the purpose of treating Staphylococcus aureus (S. aureus) chronic wound infections have several advantages. These include adhesiveness to infection site, reduced frequency of dressings, sustained drug release, inhibition of bacterial growth, and increased healing. In the present work tigecycline nanoparticles were loaded into chitosan-platelet-rich plasma (PRP) hydrogel. The tigecycline nanoparticles (95 ± 13 nm) were synthesized through ionic cross-linking method using chitosan, tripolyphosphate, and tigecycline and characterized by dynamic light scattering (DLS), scanning electron microscope (SEM), and Fourier transform infrared spectroscopy (FT-IR). The synthesized nanoparticles and activated PRP powder were mixed with chitosan hydrogel to form a homogeneous gel. Rheology studies have confirmed the shear thinning property, thermal stability, and injectability of the prepared gel systems. The gel system was further assessed for its drug release property and found that it was released in a sustained manner. Hemolysis and blood-clotting assays demonstrated that the gel system was neither a hemolysin nor a hamper to the clotting cascade. Cell viability results showed that these nanoparticles were cyto-compatible. The bioactivity of PRP loaded chitosan gel toward fibroblast cell line was studied using cell proliferation and migration assay. In vitro antibacterial studies revealed that the gel system inhibited bacterial growth to a great extent. The antibacterial activity was further analyzed using ex vivo porcine skin assay. In vivo anti-Staphylococcal activity of the prepared hydrogels was studied using a Drosophila melanogaster infection model. The tigecycline and tigecycline nanoparticle incorporated chitosan gel showed a significant antibacterial activity against S. aureus. Thus, the gel system is an effective medium for antibiotic delivery and can be applied on the infection sites to effectively forestall various skin infections caused by S. aureus.
与目前的治疗方式相比，将载有抗生素包裹纳米颗粒的可注射水凝胶系统用于治疗金黄色葡萄球菌（S. aureus）慢性伤口感染具有几个优点。这些优点包括对感染部位的粘附性、减少敷料更换的频率、药物持续释放、抑制细菌生长和促进愈合。在本工作中，替加环素纳米颗粒被加载到壳聚糖-富含血小板的血浆（PRP）水凝胶中。替加环素纳米颗粒（95 ± 13nm）是通过离子交联法使用壳聚糖、三聚磷酸钠和替加环素合成的，并通过动态光散射（DLS）、扫描电子显微镜（SEM）和傅里叶变换红外光谱（FT-IR）进行了表征。合成的纳米颗粒和激活的 PRP 粉末与壳聚糖水凝胶混合形成均匀的凝胶。流变学研究证实了所制备的凝胶系统具有剪切稀化特性、热稳定性和可注射性。进一步评估了凝胶系统的药物释放特性，发现其释放方式是持续的。溶血和凝血试验表明，该凝胶系统既不是溶血剂，也不妨碍凝血级联反应。细胞活力结果表明，这些纳米颗粒具有细胞相容性。使用细胞增殖和迁移试验研究了负载 PRP 的壳聚糖凝胶对成纤维细胞系的生物活性。体外抗菌研究表明，该凝胶系统在很大程度上抑制了细菌的生长。进一步使用离体猪皮试验分析了其抗菌活性。使用黑腹果蝇感染模型研究了所制备的水凝胶对金黄色葡萄球菌的体内抗金黄色葡萄球菌活性。载有替加环素的壳聚糖凝胶和载有替加环素纳米颗粒的壳聚糖凝胶对金黄色葡萄球菌表现出显著的抗菌活性。因此，该凝胶系统是一种有效的抗生素输送介质，可以应用于感染部位，有效地预防由金黄色葡萄球菌引起的各种皮肤感染。
