Molecular Dynamics Simulation, Characterization and In Vitro Drug Release of Isoniazid Loaded Poly-ε-caprolactone Magnetite Nanocomposite

Background: This study reports on the development of a controlled-release isoniazid (INH) drug delivery system using poly-є-caprolactone (PCL) functionalized magnetite-nanoparticles (MNPs), as a theoretical potential tool for tuberculosis (TB) chemotherapy.
Method: The magnetite Fe3O4 core was fabricated by the co-precipitation method and coated with PCL by emulsion polymerization. INH was loaded onto the PCL-MNP surface to shape an INH-PCL-MNP nanocomposite. Deposing the INH on the nanocomposite surface was demonstrated through the molecular dynamics simulations. To investigate the stability of the polymer, the root-mean-square deviation (RMSD) and the radius of gyration (Rg) were calculated. The composite was characterized by Scanning electron microscopy (SEM) and X-Ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR). Mycobacterium tuberculosis was used to assess the antimicrobial activity of the nanoparticles. The drug loading efficiency, drug content, and in-vitro release behavior of the INH-PCL-MNPs were evaluated by UV–Vis spectrophotometry.
Results: RMSD of PCL show that the structure of polymer after 40 ns is stable. INH molecules interested to spend more time close to the polymer. Rg of PCL indicated that PCL folded and radius of gyration changed near 1nm. The drug loading efficiency and drug content of the NPs were 720±46 mg/g and 69.3±3.8 (%), respectively. The compound showed a strong level of activity in-vitro. The amount of drug release at all times was above the minimum inhibitory concentration (MIC) (6 μg/ml).
Conclusion: INH-PCL-MNP nanocomposite have been effectively used as a potential tool to treat TB infections and a magnetic drug carrier system.