title: Development of a highly biocompatible antituberculosis nanodelivery formulation based on para-aminosalicylic acid-zinc layered hydroxide nanocomposites.
abstract: Tuberculosis is a lethal epidemic, difficult to control disease, claiming thousands of lives every year. We have developed a nanodelivery formulation based on para-aminosalicylic acid (PAS) and zinc layered hydroxide using zinc nitrate salt as a precursor. The developed formulation has a fourfold higher efficacy of PAS against mycobacterium tuberculosis with a minimum inhibitory concentration (MIC) found to be at 1.40 μg/mL compared to the free drug PAS with a MIC of 5.0 μg/mL. The newly developed formulation was also found active against Gram-positive bacteria, Gram-negative bacteria, and Candida albicans. The formulation was also found to be biocompatible with human normal lung cells MRC-5 and mouse fibroblast cells-3T3. The in vitro release of PAS from the formulation was found to be sustained in a human body simulated phosphate buffer saline (PBS) solution at pH values of 7.4 and 4.8. Most importantly the nanocomposite prepared using zinc nitrate salt was advantageous in terms of yield and free from toxic zinc oxide contamination and had higher biocompatibility compared to one prepared using a zinc oxide precursor. In summary, these promising in vitro results are highly encouraging for the continued investigation of para-aminosalicylic acid and zinc layered hydroxide nanocomposites in vivo and eventual preclinical studies.
authors: Materials Synthesis and Characterization Laboratory, Institute of Advanced Technology(ITMA), Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia.
authors: Bullo
authors: 0000-0002-0470-6292
authors: B
authors: Saifullah
authors: Laboratory of Vaccines and Immunotherapeutics, Institute of Bioscience, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia.
authors: Palanisamy
authors: P
authors: Arulselvan
authors: Laboratory of Vaccines and Immunotherapeutics, Institute of Bioscience, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia ; Department of Environmental Health, Faculty of Public Health and Tropical Medicine, Jazan University, Jazan, Saudi Arabia.
authors: Mohamed Ezzat
authors: ME
authors: El Zowalaty
authors: Laboratory of Vaccines and Immunotherapeutics, Institute of Bioscience, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia ; Department of Human Anatomy, Faculty of Medicine and Health Science, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia.
authors: Sharida
authors: S
authors: Fakurazi
authors: Department of Chemical Engineering and Program in Bioengineering, Northeastern University, Boston, MA 02115, USA ; Center of Excellence for Advanced Materials Research, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
authors: Thomas J
authors: TJ
authors: Webster
authors: Department of Chemical Engineering and Program in Bioengineering, Northeastern University, Boston, MA 02115, USA.
authors: Benjamin
authors: B
authors: Geilich
authors: Materials Synthesis and Characterization Laboratory, Institute of Advanced Technology(ITMA), Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia.
authors: Mohd Zobir
authors: MZ
authors: Hussein
mesh_terms: D016475:3T3 Cells; D010131:Aminosalicylic Acid / Q000737:chemistry*; D000818:Animals; D000995:Antitubercular Agents / Q000008:administration & dosage* / Q000737:chemistry* / Q000633:toxicity; D001672:Biocompatible Materials; D002460:Cell Line; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D003692:Delayed-Action Preparations; D016503:Drug Delivery Systems; D006801:Humans; D006878:Hydroxides / Q000737:chemistry*; D007700:Kinetics; D051379:Mice; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D053761:Nanocomposites / Q000737:chemistry* / Q000648:ultrastructure; D009566:Nitrates / Q000737:chemistry; D010316:Particle Size; D017550:Spectroscopy, Fourier Transform Infrared; D013499:Surface Properties; D013818:Thermogravimetry; D014961:X-Ray Diffraction; D015032:Zinc / Q000737:chemistry*; D017967:Zinc Compounds / Q000737:chemistry; D015034:Zinc Oxide / Q000737:chemistry
chemical_list: D000995:Antitubercular Agents; D001672:Biocompatible Materials; D003692:Delayed-Action Preparations; D006878:Hydroxides; D009566:Nitrates; D017967:Zinc Compounds; D010131:Aminosalicylic Acid; C042103:zinc nitrate; D015032:Zinc; D015034:Zinc Oxide