Development of a novel anti-tuberculosis nanodelivery formulation using magnesium layered hydroxide as the nanocarrier and pyrazinamide as a model drug

Abstract

Designing and synthesizing biodegradable drug delivery systems are key research areas in biomedical nanotechnology. Here, we report the development of biodegradable magnesium-layered hydroxide (MgLH) based nanodelivery systems using magnesium oxide (MgO) as the precursor by a precipitation method. The designed nanocarrier does not contain any trivalent metal ions, which are most commonly used for the synthesis of layered double hydroxides (LDHs). The designed delivery system was characterized in detail using X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, Thermogravimetric analysis (TGA), Transmission electron microscopy (TEM) and inductively coupled plasma (ICP) analyses. The anti-tuberculosis (anti-TB) drug pyrazinamide (PZA) was successfully intercalated into interlayer galleries of MgLH, resulting in the formation of the nanocomposite, PZA-MgLH, having an average size of about 107 ± 24 nm with a uniform circular shape. The in vitro release of PZA in a human body simulated phosphate buffer saline (PBS) solution was sustained (i.e., almost 66 h) and followed a pseudo-secondorder kinetic model. Moreover, the designed nanodelivery system was found to be highly biocompatible with human normal lung cells (MRC-5) and with 3T3 fibroblast cells as controls for 24 and 48 h. Lastly, the PZA-MgLH nanocomposite showed good anti-tuberculosis activity against Mycobacterium tuberculosis and both the PZA-MgLH nanocomposite and its released free drug PZA showed antibacterial activity against tested Gram-positive and Gram-negative bacteria with percentage inhibition ranging from 5.6% to 68% against S. aureus, E. coli, and P. aeruginosa for the PZA free drug, and 32% to 32.5% against E. coli for the PZA-MgLH nanocomposite. In summary, the present results provide significant evidence that the designed nanodelivery system can be used for the delivery of PZA and, thus, should be investigated further for a wide range of anti-TB applications.