Targeted delivery of antibiotics to intracellular chlamydial infections using PLGA nanoparticles.
Targeted delivery of antibiotics to intracellular chlamydial infections using PLGA nanoparticles.
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DOI：
10.1016/j.biomaterials.2011.05.038
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发表时间：
2011-09
期刊：
影响因子：
14
通讯作者：
Whittum-Hudson, Judith A.
中科院分区：
文献类型：
--
作者：
Toti, Udaya S.;Guru, Bharath R.;Hali, Mirabela;McPharlin, Christopher M.;Wykes, Susan M.;Panyam, Jayanth;Whittum-Hudson, Judith A.
关键词：
沙眼衣原体和肺炎衣原体是细胞内的细菌病原体，已被证明会引起多种慢性疾病或与多种慢性疾病密切相关。这两种微生物的持续感染对抗生素治疗是难治的。缺乏治疗功效是由于持续感染披衣菌的代谢率减弱，加上正常递送抗生素至宿主细胞质中存在披衣菌的内含物所能达到的适度细胞内药物浓度。在这项研究中，我们评估了使用可生物降解的聚（d-L-丙交酯-共-乙交酯）（PLGA）聚合物配制的纳米颗粒是否可以增强抗生素向衣原体包合物的递送。我们最初研究了PLGA纳米颗粒在衣原体感染细胞中的运输。然后，我们评估了纳米颗粒将抗生素递送到内含物。细胞内运输研究表明，PLGA纳米颗粒有效地集中在急性和持续感染细胞的内含物中。此外，在PLGA纳米颗粒中封装利福平和阿奇霉素抗生素增强了抗生素在减少微生物负荷方面的有效性。利福平和阿奇霉素联合用药比单独用药更有效。总体而言，我们的研究表明，PLGA纳米颗粒可以成为有效的载体，用于靶向递送抗生素到细胞内衣原体感染。
Chlamydia trachomatis and C 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.
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