Amrita Center for Nanosciences and Molecular Medicine, Amrita Institute of Medical Sciences and Research Centre, Amrita Vishwa Vidyapeetham University, Kochi 682041, India.
Amrita Center for Nanosciences and Molecular Medicine, Amrita Institute of Medical Sciences and Research Centre, Amrita Vishwa Vidyapeetham University, Kochi 682041, India.
Int J Biol Macromol. 2015 Mar;74:36-43. doi: 10.1016/j.ijbiomac.2014.11.006. Epub 2014 Dec 2.
Polymorphonuclear leukocytes (PMNs) provide the primary host defence against invading pathogens by producing reactive oxygen species (ROS) and microbicidal products. However, few pathogens can survive for a prolonged period of time within the PMNs. Additionally their intracellular lifestyle within the PMNs protect themselves from the additional lethal action of host immune systems such as antibodies and complements. Antibiotic delivery into the intracellular compartments of PMNs is a major challenge in the field of infectious diseases. In order to deliver antibiotics within the PMNs and for the better treatment of intracellular bacterial infections we synthesized rifampicin (RIF) loaded amorphous chitin nanoparticles (RIF-ACNPs) of 350±50 nm in diameter. RIF-ACNPs nanoparticles are found to be non-hemolytic and non-toxic against a variety of host cells. The release of rifampicin from the prepared nanoparticles was ∼60% in 24 h, followed by a sustained pattern till 72 h. The RIF-ACNPs nanoparticles showed 5-6 fold enhanced delivery of RIF into the intracellular compartments of PMNs. The RIF-ACNPs showed anti-microbial activity against Escherichia coli, Staphylococcus aureus and a variety of other bacteria. In summary, our results suggest that RIF-ACNPs could be used to treat a variety of intracellular bacterial infections.
多形核白细胞 (PMN) 通过产生活性氧 (ROS) 和杀菌产物来提供针对入侵病原体的主要宿主防御。然而，很少有病原体能够在 PMN 内长时间存活。此外，它们在 PMN 内的细胞内生活方式使它们免受宿主免疫系统（如抗体和补体）的额外致命作用的影响。将抗生素递送到 PMN 的细胞内隔室是传染病领域的一个主要挑战。为了在 PMN 内递送抗生素并更好地治疗细胞内细菌感染，我们合成了直径为 350±50nm 的载有利福平 (RIF) 的无定形壳聚糖纳米颗粒 (RIF-ACNPs)。RIF-ACNPs 纳米颗粒被发现对多种宿主细胞既没有溶血作用也没有毒性。从制备的纳米颗粒中释放的利福平在 24 小时内约为 60%，随后持续至 72 小时。RIF-ACNPs 纳米颗粒将利福平递送到 PMN 细胞内隔室的效率提高了 5-6 倍。RIF-ACNPs 对大肠杆菌、金黄色葡萄球菌和多种其他细菌表现出抗菌活性。总之，我们的结果表明，RIF-ACNPs 可用于治疗多种细胞内细菌感染。
