International Journal of Pharmaceutics 385 (2010) 143–149 Contents lists available at ScienceDirect International Journal of Pharmaceutics journal homepage: www.elsevier.com/locate/ijpharm Pharmaceutical Nanotechnology Gelatin nanocarriers as potential vectors for effective management of tuberculosis Gaurav Kant Saraogi a , Puspa Gupta b , U.D. Gupta b , N.K. Jain a , G.P. Agrawal a,∗ a Pharmaceutics Research Laboratory, Department of Pharmaceutical Sciences, Dr. H.S. Gour University, Sagar, MP 470003, India b National JALMA Institute for Leprosy and Other Mycobacterial Diseases (ICMR), Agra, UP 282001, India article info Article history: Received 1 July 2009 Received in revised form 26 September 2009 Accepted 1 October 2009 Available online 9 October 2009 Keywords: Rifampicin Tuberculosis Drug delivery Nanoparticles Gelatin nanoparticles abstract The aim of the research work was to develop and characterize rifampicin (RIF) loaded gelatin nanoparticu- late delivery system for the effective management of tuberculosis. Gelatin nanoparticles (GPs) containing RIF were prepared using two-step desolvation method. Formulations were characterized through trans- mission electron microscopy (TEM), atomic force microscopy (AFM), size and size distribution analysis, polydispersity index (PDI), zeta potential, percent drug entrapment, percent nanoparticulate yield and in vitro drug release. Formulations were further characterized for in vitro cytotoxicity, in vivo biodistri- bution, and antitubercular activity. The nanoparticles were found to be spherical in shape. The size of nanoparticles was found to be 264 ± 11.2 nm with low PDI suggesting the narrow particle size distribu- tion. The drug release showed the biphasic pattern of release i.e. initial burst followed by a sustained release pattern. The cytotoxicity studies revealed that nanoparticles are safe, non toxic as compared to free drug. In vivo biodistribution study showed higher localization of RIF loaded GPs in various organs, as compared to plain RIF solution in PBS (pH 7.4). In contrast to free drug, the nanoparticles not only sustained the plasma level but also enhanced the AUC and mean residence time (MRT) of the drug, suggesting improved pharmacokinetics of drug. RIF GPs additionally resulted in significant reduction in bacterial counts in the lungs and spleen of TB-infected mice. Hence, GPs hold promising potential for increasing drug targetability vis a vis reducing dosing frequency with the interception of minimal side effects, for efficient management of tuberculosis. © 2009 Elsevier B.V. All rights reserved. 1. Introduction Tuberculosis (TB) is the leading infectious killer of youth and adults worldwide due to a single infectious agent and the second most common cause of death amongst infectious diseases, after acquired immunodeficiency syndrome (AIDS). Approximately one- third of the world population—i.e. two billion people are, infected with Mycobacterium tuberculosis (M. tuberculosis), more than eight million people develop TB every year, and approximately two mil- lion die annually (World Health Organization, 2006; Gupta and Katoch, 2009). Although effective drugs are available for treat- ment of TB, yet daily multiple drug therapy for several months, poor patient compliance, drug toxicity and emergence of multi drug resistance lead to failure of chemotherapy (Toit et al., 2006). Rifampicin (RIF) is first line drug currently used for treatment of latent M. tuberculosis infection in adults. But a number of side effects like lack of appetite, nausea, hepatotoxicity, fever, chill, allergic rashes, itching and immunological disturbances, patient ∗ Corresponding author. Tel.: +91 9424450204. E-mail address: gpagrawal2005@rediffmail.com (G.P. Agrawal). non-compliance in long term therapy limit its use (Barrow et al., 1998; Laura et al., 2000). Thus, the current strategy for enhanc- ing the therapeutic activity of currently available drugs is to entrap drugs within a delivery system from where they are slowly released over an extended time period (Gelperina et al., 2005). Novel drug carrier systems play an important role in controlled delivery of a pharmaceutical agent to the target at therapeutically optimal rate and dose. Several reports are available regarding the use of carrier systems like liposomes, dendrimers, microspheres, solid lipid nanoparticles for delivery of bioactives. Amongst various drug delivery systems, nanoparticles (NPs) represent a very promising approach for deliver bioactives (Deol and Khuller, 1997; Kreuter, 2004; Pandey and Khuller, 2005; Kumar et al., 2006). Nanoparticles represent a class of drug delivery vehicles which can serve as promising perspective for ferrying large doses of the drug to the target site with interception of minimal side effects. As a drug delivery carrier they offer several advantages, such as ease of purification and sterilization, possibility of drug targeting, and a sustained release action (Soppimath et al., 2001; Gelperina et al., 2005; Kisich et al., 2007; Pandey and Khuller, 2007; Ahmad et al., 2008). Targeted drug delivery systems can optimize the therapeutic index of antitubercular drugs by increasing the drug concentra- 0378-5173/$ – see front matter © 2009 Elsevier B.V. All rights reserved. doi:10.1016/j.ijpharm.2009.10.004