Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, MN 55455, USA.
Biomaterials. 2011 Sep;32(27):6606-13. doi: 10.1016/j.biomaterials.2011.05.038. Epub 2011 Jun 8.
Chlamydia trachomatis and Chlamydia pneumoniae are intracellular bacterial pathogens that have been shown to cause, or are strongly associated with, diverse chronic diseases. Persistent infections by both organisms are refractory to antibiotic therapy. The lack of therapeutic efficacy results from the attenuated metabolic rate of persistently infecting chlamydiae in combination with the modest intracellular drug concentrations achievable by normal delivery of antibiotics to the inclusions within which chlamydiae reside in the host cell cytoplasm. In this research, we evaluated whether nanoparticles formulated using the biodegradable poly(d-L-lactide-co-glycolide) (PLGA) polymer can enhance the delivery of antibiotics to the chlamydial inclusion complexes. We initially studied the trafficking of PLGA nanoparticles in Chlamydia-infected cells. We then evaluated nanoparticles for the delivery of antibiotics to the inclusions. Intracellular trafficking studies show that PLGA nanoparticles efficiently concentrate in inclusions in both acutely and persistently infected cells. Further, encapsulation of rifampin and azithromycin antibiotics in PLGA nanoparticles enhanced the effectiveness of the antibiotics in reducing microbial burden. Combination of rifampin and azithromycin was more effective than the individual drugs. Overall, our studies show that PLGA nanoparticles can be effective carriers for targeted delivery of antibiotics to intracellular chlamydial infections.
沙眼衣原体和肺炎衣原体是胞内细菌病原体，已被证明可引起或与多种慢性疾病密切相关。这两种病原体的持续感染对抗生素治疗有抗性。缺乏治疗效果是由于持续感染的衣原体代谢率降低，以及抗生素通过正常途径递送至宿主细胞质中衣原体所在的包含体中的细胞内药物浓度适中。在这项研究中，我们评估了使用可生物降解的聚（D-丙交酯-共-乙交酯）（PLGA）聚合物制成的纳米颗粒是否可以增强抗生素向衣原体包含物复合物的递送。我们首先研究了 PLGA 纳米颗粒在感染衣原体的细胞中的转运。然后，我们评估了纳米颗粒将抗生素递送至包含物的能力。细胞内转运研究表明，PLGA 纳米颗粒在急性和持续性感染细胞中均能有效地在包含物中浓缩。此外，将利福平（rifampin）和阿奇霉素（azithromycin）抗生素包封在 PLGA 纳米颗粒中增强了抗生素降低微生物负担的效果。利福平与阿奇霉素联合使用比单独使用这两种药物更有效。总的来说，我们的研究表明，PLGA 纳米颗粒可以作为靶向递送至细胞内衣原体感染的有效载体。
