219 Introduction Infectious diseases caused by intracellular bacteria represent a challenge for current antimicrobial thera- pies because of the requirement that antibiotics reach therapeutic concentrations at the site of infection. Tuberculosis (TB) is the second most common infectious disease and leading infectious cause of death of youth and adults worldwide. In 2006, an estimated 9.2 million incident cases and approximately 1.7 million deaths due to TB occurred worldwide making it the world’s leading causes of mortality (WHO report, 2008). Many antibiotics which are highly active during in vitro experiments are often inactive against intracellular bacteria, due to their poor penetration into the cells or to their inactivation by lysosomal enzymes (van den Broek et al., 1986). One approach to overcoming this problem consists of using drug carriers capable of enhancing the intracellular delivery of antimicrobial agents (Couvreur et al., 1991; Swenson et al., 1990; Desiderio & Campbell, 1983). One of the major problems is noncompliance to pre- scribed regimens, primarily because treatment of TB involves continuous, frequent multiple drug dosing. TB management may be improved with the introduction of longer acting formulations releasing the antimicrobial agents in a slow and sustained manner, which would allow reduction in frequency and dosing numbers (Ahmad et al., 2008; Pandey et al., 2006). Isoniazid (INH), the first line antitubercular agent is readily distributed into alveolar cells to inhibit the growth of tubercle bacilli. e conventional oral admin- istration of INH can not maintain its effective minimum inhibitory concentration for a longer period of time, and ORIGINAL ARTICLE Mannosylated gelatin nanoparticles bearing isoniazid for effective management of tuberculosis Gaurav Kant Saraogi 1 , Bhavna Sharma 2 , Beenu Joshi 2 , Pushpa Gupta 2 , Umesh Dutta Gupta 2 , Narendra Kumar Jain 1 , and Govind Prasad Agrawal 1 1 Pharmaceutics Research Laboratory, Department of Pharmaceutical Sciences, Dr. H.S. Gour University, Sagar, Madhya Pradesh, India, and 2 National JALMA Institute for Leprosy and Other Mycobacterial Diseases (ICMR), Agra, Uttar Pradesh, India 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. Keywords: Tuberculosis, mannose, isoniazid, targeting, alveolar macrophages Address for Correspondence: Prof. G. P. Agrawal, Pharmaceutics Research Laboratory, Department of Pharmaceutical Sciences, Dr. H. S. Gour University, Sagar, 470 003, Madhya Pradesh, India. E-mail: gpagrawal2004@yahoo.co.in (Received 30 November 2009; revised 15 March 2010; accepted 04 May 2010) Journal of Drug Targeting, 2011; 19(3): 219–227 © 2011 Informa UK, Ltd. ISSN 1061-186X print/ISSN 1029-2330 online DOI: 10.3109/1061186X.2010.492522