title: Development and Characterization of Nanoembedded Microparticles for Pulmonary Delivery of Antitubercular Drugs against Experimental Tuberculosis.
abstract: The foremost objective of the present research study was to develop and evaluate the potential of rifampicin (RIF) and isoniazid (INH) loaded spray dried nanoembedded microparticles against experimental tuberculosis (TB). In this study, RIF-INH loaded various formulations (chitosan, guar gum, mannan, and guar gum coated chitosan) were prepared by spray drying and characterized on the basis of in vitro as well as in vivo studies. Results showed that guar gum spray dried particles showed uniform size distribution with smooth surface as compare to mannan formulations. Guar gum batches exhibited excellent flow ability attributed to their optimum moisture content and uniform size distribution. The drug release showed the biphasic pattern of release, i.e., initial burst followed by a sustained release pattern. The preferential uptake of guar gum coated formulations suggested the presence and selective uptake capability of mannose moiety to the specific cell surface of macrophages. In vivo lung distribution study showed that guar gum coated chitosan (GCNP) batches demonstrated prolonged residence at the target site and thereby improve the therapeutic utility of drug with a significant reduction in systemic toxicity. Optimized drug loaded GCNP formulation has resulted in almost 5-fold reduction of the number of bacilli as compared to control group. Histopathology study also demonstrated that none of the treated groups show any evidence of lung tissue abnormality. Hence, GCNPs could be a promising carrier for selective delivery of antitubercular drugs to alveolar macrophages with the interception of minimal side effects, for efficient management of TB.
authors.affiliation: Nanomedicine Research Centre, Department of Pharmaceutics, ISF College of Pharmacy , Moga, Punjab, India.
authors.forename: Amit Kumar
authors.initials: AK
authors.lastname: Goyal
authors.affiliation: Nanomedicine Research Centre, Department of Pharmaceutics, ISF College of Pharmacy , Moga, Punjab, India.|Punjab Technical University , Kapurthala, Punjab, India.
authors.forename: Tarun
authors.initials: T
authors.lastname: Garg
authors.affiliation: Nanomedicine Research Centre, Department of Pharmaceutics, ISF College of Pharmacy , Moga, Punjab, India.|Punjab Technical University , Kapurthala, Punjab, India.
authors.forename: Goutam
authors.initials: G
authors.lastname: Rath
authors.affiliation: National Jalma Institute for Leprosy and Other Mycobacterial Diseases , Agra, Uttar Pradesh, India.
authors.forename: Umesh Datta
authors.initials: UD
authors.lastname: Gupta
authors.affiliation: National Jalma Institute for Leprosy and Other Mycobacterial Diseases , Agra, Uttar Pradesh, India.
authors.forename: Pushpa
authors.initials: P
authors.lastname: Gupta
mesh_terms: D000818:Animals; D000904:Antibiotics, Antitubercular / Q000494:pharmacology*; D002626:Chemistry, Pharmaceutical; D048271:Chitosan / Q000737:chemistry; D020099:Coated Materials, Biocompatible / Q000008:administration & dosage / Q000737:chemistry*; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D016503:Drug Delivery Systems; D005260:Female; D005685:Galactans / Q000737:chemistry; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000382:microbiology; D008351:Mannans / Q000737:chemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D009161:Mycobacterium / Q000472:pathogenicity; D053769:Nanocapsules; D053149:Plant Gums / Q000737:chemistry; D012293:Rifampin / Q000494:pharmacology*; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy* / Q000382:microbiology
chemical_list: D000904:Antibiotics, Antitubercular; D020099:Coated Materials, Biocompatible; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D005685:Galactans; D008351:Mannans; D053769:Nanocapsules; D053149:Plant Gums; D048271:Chitosan; C007894:guar gum; D012293:Rifampin
keywords: alveolar macrophages; challenge studies; guar gum coated chitosan; nanoembedded microparticles; pulmonary drug delivery; tuberculosis