A Novel Para-Amino Salicylic Acid Magnesium Layered Hydroxide Nanocomposite Anti-Tuberculosis Drug Delivery System with Enhanced in vitro Therapeutic and Anti-Inflammatory Properties

Abstract

Introduction:Mycobacterium tuberculosis infections are associated with severe local inflammatory reactions, which may be life-threatening and lead to tuberculosis pathogenesis and associated complications. Inorganic nanolayers have been vastly exploited for biomedical applications (especially in drug delivery) because of their biocompatible and biodegradable nature with the ability to release a drug in a sustained manner. Herein, we report a new nanodelivery system of inorganic nanolayers based on magnesium layered hydroxides (MgLH) and a successfully intercalated anti-tuberculosis drug para-aminosalicylic acid (PAS). Methods: The designed anti-tuberculosis nanodelivery composite, MgLH-PAS, was prepared by a novel co-precipitation method using MgNO 3 as well MgO as starting materials. Results:The designed nano-formulation, PAS-MgLH, showed good antimycobacterial and antimicrobial activities with significant synergistic anti-inflammatory effects on the suppression of lipopolysaccharide (LPS) stimulated inflammatory mediators in RAW 264.7 macrophages. The designed nano-formulation was also found to be biocompatible with human normal lung cells (MRC-5) and 3T3 fibroblast cells. Furthermore, the in vitro release of PAS from PAS-MgLH was found to be sustained in human body simulated phosphate buffer saline (PBS) solutions of pH 7.4 and pH 4.8. Discussion: The results of the present study are highly encouraging for further in vivo studies. This new nanodelivery system, MgLH, can be exploited in the delivery of other drugs and in numerous other biomedical applications as well.

Construction of High Energy Nanoscale Lead Azide Composite with Improved Flame Sensibility from Intercalated Hydroxide

“…38,42 The increased basal spacings in SA-Pb(OH) 2 strongly suggest the successful intercalation of salicylate into the interlayer galleries of Pb(OH) 2 . 43 It needs to be added that the intensity of the diffraction peaks of Pb(OH) 2 weakens rather than disappears, indicating the existence of Pb(OH) 2 without successful intercalation. Figure 2c shows the TG-DTG curves of SA-Pb(OH) 2 .…”

“…The EDS mapping (Figure S2) of SA-Pb­(OH) 2 proves that C, O, and Pb elements are uniformly distributed on the surface of the material. As shown in the XRD patterns of SA-Pb­(OH) 2 and Pb­(OH) 2 (Figure b), the diffraction peaks of Pb­(OH) 2 obtained by coprecipitation of lead nitrate and sodium hydroxide are almost identical to the standard diffraction peak, except that two new diffraction peaks appear at the low diffraction angle, presumably due to the insertion of a small amount of NO 3 – and H 2 O in the solution into the interlayer of Pb­(OH) 2 . − However, the diffraction peaks of SA-Pb­(OH) 2 appear at 2θ angles of 6.79, 13.83, and 20.77 with a good multiplication relationship, revealing that SA-Pb­(OH) 2 with a bedded structure was successfully synthesized. − Besides, the strongest diffraction peak appears when 2θ is 6.79, corresponding to a basal spacing of 1.28 nm, which virtually is the sum of ordinary Pb­(OH) 2 basal spacing (0.61 nm) and diameter of salicylate (0.62 nm). , The increased basal spacings in SA-Pb­(OH) 2 strongly suggest the successful intercalation of salicylate into the interlayer galleries of Pb­(OH) 2 . It needs to be added that the intensity of the diffraction peaks of Pb­(OH) 2 weakens rather than disappears, indicating the existence of Pb­(OH) 2 without successful intercalation.…”

Novel Approaches for the Treatment of Drug-Resistant Tuberculosis

“…MgLH and intercalated para-aminosalicylic acid (PAS) second-line anti-TB drug has shown highly encouraging results in the study. [52] These studies highlight the remarkable potential of nanostructures with long shelf life, better bioavailability of the drugs, and better safety profiles and thus better clinical outcomes. [5]…”