Topic:

Tuberculosis and other mycobacterial infections

Abstract No.:

ISE.111

Title:

Green synthesis of Isoniazid-loaded silver-starch bionanocomposites for the treatment of tuberculosis

Author(s):

I. Obidike¹, M. Emeje², A. George³, A. Pawar⁴, S. Ofoefule⁵; ¹National Institute for Pharmaceutical Research and Development, Drug screening for Infectious diseases, Abuja/NG, ²National Institute for Pharmaceutical Research and Development (NIPRD), Nanomedicine and Biophysical Drug delivery, Abuja, ABUJA/NG, ³National Chemical Laboratory, Pune, India, Nanoscience, Pune, MAHARASHTRA/IN, ⁴ Poona College of Pharmacy, Pune, India, Pharmaceutics,, Pune/IN, ⁵University of Nigeria, Nsukka Enugu, Nigeria, Pharmaceutical Techology and Microbiology, Enugu/NG

Abstract:

Background: Tuberculosis (TB) has been declared a public health emergency by the World Health Organization (WHO). Estimates reveal that about 9 million cases occur globally, with Asia and Africa accounting for 85 %. Isoniazid (INH), an effective antituberculosis drug used in many countries is poorly absorbed from the stomach; hence, low bioavailability remains its major challenge. Application of nanotechnology to solve this problem is gaining increasing interest in this regard. However, most of the researches on carrier systems use very expensive synthetic polymers, making the dosage forms out of the reach of many in developing countries.
Methods: We isolated and purified starch from a cheap and renewable source; Manihot esculenta. The purified starch was modified to obtain acetylated starch. NMR, FTIR and Raman spectroscopies were used to confirm the synthesis, while DSC-TGA, SEM, XRD, viscosity profile, water absorption and solubility indices were used to characterize the new polymer. We also report herein the binding of INH to starch protected silver nanoparticles and its application in enhanced delivery of INH for the treatment of TB. The INH nanoparticles (INH-NPs) were evaluated for mean particle size, polydispersity index, and zeta potential and further characterized by FTIR and SEM. In vitro release of INH-NPs as well as the effect of nanoencapsulation of INH on the antibacterial activity of INH against gram-positive and gram-negative bacteria was also evaluated on BACTEC-MGIT960.  
Results: Our results show that INH-NPs were generally spherical with monodispersed size distribution. The nanoparticles were evaluated for mean particle size (245 nm), polydispersity index (0.320) and zeta potential (-18.16 mV) and further confirmed by UV, FTIR and SEM.  In vitro release of encapsulated nanoparticles showed significant rapid release profile in acidic pH of the stomach. INH-NPs exhibited minimum inhibitory concentration (MIC) value of 0.003 ug/mL, while INH-free drug had MIC value of 0.07 ug/mL. 
Conclusion: This study shows that, INH-NPs prepared from a cheap, non-toxic, renewable and generally compatible natural polymer could considerably improve the INH antibacterial efficacy, while still being more economical.