title: Targeted delivery of antibiotics to intracellular chlamydial infections using PLGA nanoparticles.
abstract: 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.
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Udaya S
authors.initials: US
authors.lastname: Toti
authors.forename: Bharath R
authors.initials: BR
authors.lastname: Guru
authors.forename: Mirabela
authors.initials: M
authors.lastname: Hali
authors.forename: Christopher M
authors.initials: CM
authors.lastname: McPharlin
authors.forename: Susan M
authors.initials: SM
authors.lastname: Wykes
authors.forename: Jayanth
authors.initials: J
authors.lastname: Panyam
authors.forename: Judith A
authors.initials: JA
authors.lastname: Whittum-Hudson
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D017963:Azithromycin / Q000494:pharmacology; D002460:Cell Line; D002626:Chemistry, Pharmaceutical; D002690:Chlamydia Infections / Q000188:drug therapy*; D002692:Chlamydia trachomatis / Q000187:drug effects; D003374:Coumarins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems / Q000379:methods*; D004357:Drug Synergism; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects / Q000382:microbiology*; D019344:Lactic Acid / Q000737:chemistry*; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects; D053758:Nanoparticles / Q000737:chemistry*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D012293:Rifampin / Q000494:pharmacology; D013997:Time Factors
chemical_list: D000900:Anti-Bacterial Agents; D003374:Coumarins; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D017963:Azithromycin; C030123:coumarin; D012293:Rifampin