title: Mannosylated gelatin nanoparticles bearing isoniazid for effective management of tuberculosis.
abstract: The mannosylated gelatin nanoparticles (Mn-GNPs) were prepared for the selective delivery of an antitubercular drug, isoniazid (INH), to the alveolar macrophages. The gelatin nanoparticles (GNPs) were prepared by using a two-step desolvation method and efficiently conjugated with mannose. Various parameters such as particle size, polydispersity index, zeta potential, % entrapment efficiency, in vitro drug release, macrophage uptake, in vivo biodistribution, antitubercular activity and hepatotoxicity of plain and Mn-GNPs were determined. The size of nanoparticles (both plain and Mn-GNPs) was found to be in range of 260-380 nm, and maximum drug payload was found to be 40-55%. Average particle size of Mn-GNPs was more, whereas drug entrapment was lesser compared to plain GNPs. The organ distribution studies demonstrated the efficiency of Mn-GNPs for spatial delivery of INH to alveolar tissues. Intravenous administration of INH loaded Mn-GNPs (I-Mn-GNPs) resulted in significant reduction in bacterial counts in the lungs and spleen of tuberculosis-infected (TB-infected) mice and also reduction in the hepatotoxicity of the drug. This study revealed that mannose conjugated GNPs may be explored as potential carrier for safer and efficient management of TB through targeted delivery of INH when compared to plain GNPs and free drug.
authors.affiliation: Pharmaceutics Research Laboratory, Department of Pharmaceutical Sciences, Dr. H.S. Gour University, Sagar, Madhya Pradesh, India.
authors.forename: Gaurav Kant
authors.initials: GK
authors.lastname: Saraogi
authors.forename: Bhavna
authors.initials: B
authors.lastname: Sharma
authors.forename: Beenu
authors.initials: B
authors.lastname: Joshi
authors.forename: Pushpa
authors.initials: P
authors.lastname: Gupta
authors.forename: Umesh Dutta
authors.initials: UD
authors.lastname: Gupta
authors.forename: Narendra Kumar
authors.initials: NK
authors.lastname: Jain
authors.forename: Govind Prasad
authors.initials: GP
authors.lastname: Agrawal
mesh_terms: D000818:Animals; D000995:Antitubercular Agents / Q000032:analysis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D004337:Drug Carriers; D004339:Drug Compounding; D005079:Excipients; D005260:Female; D005780:Gelatin / Q000737:chemistry* / Q000378:metabolism; D007538:Isoniazid / Q000032:analysis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D008358:Mannose / Q000737:chemistry* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009164:Mycobacterium Infections / Q000188:drug therapy; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D013499:Surface Properties; D014376:Tuberculosis / Q000188:drug therapy*
chemical_list: D000995:Antitubercular Agents; D004337:Drug Carriers; D005079:Excipients; D005780:Gelatin; D008358:Mannose; D007538:Isoniazid