title: Comparative efficacy of chloramphenicol loaded chondroitin sulfate and dextran sulfate nanoparticles to treat intracellular Salmonella infections.
abstract: Salmonella Paratyphi A is a food-borne Gram-negative pathogen and a major public health challenge in the developing world. Upon reaching the intestine, S. Paratyphi A penetrates the intestinal epithelial barrier; and infects phagocytes such as macrophages and dendritic cells. S. Paratyphi A surviving within macrophages is protected from the lethal action of antibiotics due to their poor penetration into the intracellular compartments. Hence we have developed chloramphenicol loaded chondroitin sulfate (CS-Cm Nps) and dextran sulfate (DS-Cm Nps) nanoparticles through ionotropic-gelation method for the intracellular delivery of chloramphenicol. The size of these nanoparticles ranged between 100 and 200 nm in diameter. The encapsulation efficiency of both the nanoparticles was found to be around 65%. Both the nanoparticles are found to be non-hemolytic and non-toxic to fibroblast and epithelial cells. The prepared nanoparticles exhibited sustained release of the drug of up to 40% at pH 5 and 20-25% at pH 7.0 after 168 h. The anti-microbial activities of both nanoparticles were tested under in vitro and ex vivo conditions. The delivery of DS-Cm Nps into the intracellular compartments of the macrophages was 4 fold more compared to the CS-Cm Nps which lead to the enhanced intracellular antimicrobial activity of Ds-Cm Nps. Enhanced anti-microbial activity of Ds-Cm Nps was further confirmed in an ex vivo chicken intestine infection model. Our results showed that Cm loaded DS Nps can be used to treat intracellular Salmonella infections.
authors: Amrita Centre for Nanosciences and Molecular Medicine, Amrita Institute of Medical Science and Research Centre, Amrita Vishwa Vidyapeetham University, Kochi 682041, India.
authors: V
authors: V
authors: Kiruthika
authors: Amrita Centre for Nanosciences and Molecular Medicine, Amrita Institute of Medical Science and Research Centre, Amrita Vishwa Vidyapeetham University, Kochi 682041, India.
authors: S
authors: S
authors: Maya
authors: Amrita Centre for Nanosciences and Molecular Medicine, Amrita Institute of Medical Science and Research Centre, Amrita Vishwa Vidyapeetham University, Kochi 682041, India.
authors: Maneesha K
authors: MK
authors: Suresh
authors: Department of Microbiology, Amrita Institute of Medical Sciences and Research Centre, Amrita Vishwa Vidyapeetham University, Kochi 682041, India.
authors: V Anil
authors: VA
authors: Kumar
authors: Amrita Centre for Nanosciences and Molecular Medicine, Amrita Institute of Medical Science and Research Centre, Amrita Vishwa Vidyapeetham University, Kochi 682041, India. Electronic address: rjayakumar@aims.amrita.edu.
authors: R
authors: R
authors: Jayakumar
authors: Amrita Centre for Nanosciences and Molecular Medicine, Amrita Institute of Medical Science and Research Centre, Amrita Vishwa Vidyapeetham University, Kochi 682041, India. Electronic address: rajabiswas@aims.amrita.edu.
authors: Raja
authors: R
authors: Biswas
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D002701:Chloramphenicol / Q000494:pharmacology / Q000627:therapeutic use*; D002809:Chondroitin Sulfates / Q000737:chemistry*; D016264:Dextran Sulfate / Q000737:chemistry*; D004705:Endocytosis / Q000187:drug effects; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D042541:Intracellular Space / Q000382:microbiology*; D051379:Mice; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D051381:Rats; D012480:Salmonella Infections / Q000188:drug therapy*; D017550:Spectroscopy, Fourier Transform Infrared; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D002701:Chloramphenicol; D002809:Chondroitin Sulfates; D016264:Dextran Sulfate
keywords: Chloramphenicol; Chondroitin sulfate nanoparticles; Dextran sulfate nanoparticles; Intracellular delivery; Salmonella