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

Saifullah B, Arulselvan P, El Zowalaty ME, Tan WS, Fakurazi S, Webster TJ, et al.

Int J Nanomedicine, 2021;16:7035-7050.
PMID: 34703226 DOI: 10.2147/IJN.S297040

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 MgNO3 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.

Matched MeSH terms: Aminosalicylic Acid*
Analyzing seismogram of the earthquake C051099C, PNGon UGM, PMG and CHTO observation stations to understand the S and P wave velocity Structure

Santosa BJ

Sains Malaysiana, 2009;38.

This research, compares the observed seismogram of the PNG earthquake, C051099C with its synthetics in UGM, Wanagama, Indonesia, PMG, Port Moresby, PNG and CHTO, Chiang May, Thailand. The synthetic seismogram is calculated using preliminary earth model, which are the IASPEI91 and the anisotropic version of PREM. The seismogram comparison is conducted after imposing a low pass filter whose corner frequency is fixed at 20 mHz. We have found a real discrepancy on the travel time and waveform of some wave phases, namely P, S and Rayleigh and Love surface waves, by seismogram comparison in time domain. To correct the discrepancies, we need to adjust the earth structures, which include the depth of the Moho reflector, the velocity gradient of bh, and the propagation velocity of the P and S waves. The correction has been conducted in the earth layering system from the upper mantle down to the CMB, so that the excellent seismogram fitting was obtained for nearly all phases of the targeted waves. The used wave length for analysing is about 150 km. It turns out that the waveform of the body and surface waves is sensitive to the change of velocity structure. The analysis of repetitive ScS depth phases at closer distance stations gives better opportunity to investigate the S velocity structure near the CMB, something not used by other seismologists.

Matched MeSH terms: Aminosalicylic Acid
Fulltext Antituberculosis nanodelivery system with controlled-release properties based on para-amino salicylate-zinc aluminum-layered double-hydroxide nanocomposites

Saifullah B, Hussein MZ, Hussein-Al-Ali SH, Arulselvan P, Fakurazi S

Drug Des Devel Ther, 2013;7:1365-75.
PMID: 24255593 DOI: 10.2147/DDDT.S50665

We report the intercalation and characterization of para-amino salicylic acid (PASA) into zinc/aluminum-layered double hydroxides (ZLDHs) by two methods, direct and indirect, to form nanocomposites: PASA nanocomposite prepared by a direct method (PASA-D) and PASA nanocomposite prepared by an indirect method (PASA-I). Powder X-ray diffraction, Fourier-transform infrared spectroscopy, and thermogravimetric analysis revealed that the PASA drugs were accommodated within the ZLDH interlayers. The anions of the drug were accommodated as an alternate monolayer (along the long-axis orientation) between ZLDH interlayers. Drug loading was estimated to be 22.8% and 16.6% for PASA-D and PASA-I, respectively. The in vitro release properties of the drug were investigated in physiological simulated phosphate-buffered saline solution of pH 7.4 and 4.8. The release followed the pseudo-second-order model for both nanocomposites. Cell viability (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide [MTT] assays) was assessed against normal human lung fibroblast MRC-5 and 3T3 mouse fibroblast cells at 24, 48, and 72 hours. The results showed that the nanocomposite formulations did not possess any cytotoxicity, at least up to 72 hours.

Matched MeSH terms: Aminosalicylic Acid/administration & dosage*; Aminosalicylic Acid/chemistry
Asian Organization for Crohn's and Colitis and Asia Pacific Association of Gastroenterology practice recommendations for medical management and monitoring of inflammatory bowel disease in Asia

Ran Z, Wu K, Matsuoka K, Jeen YT, Wei SC, Ahuja V, et al.

J Gastroenterol Hepatol, 2021 Mar;36(3):637-645.
PMID: 32672839 DOI: 10.1111/jgh.15185

Inflammatory bowel disease (IBD) has increased in incidence and prevalence in Asian countries since the end of the 20th century. Moreover, differences in the cause, phenotypes, and natural history of IBD between the East and West have been recognized. Therefore, the Asian Organization for Crohn's and Colitis and the Asia Pacific Association of Gastroenterology have established recommendations on medical management of IBD in Asia. Initially, the committee members drafted 40 recommendations, which were then assessed according to Grading of Recommendations Assessment, Development and Evaluation. Eight statements were rejected as this indicated that consensus had not been reached. The recommendations encompass pretreatment evaluation; medical management of active IBD; medical management of IBD in remission; management of IBD during the periconception period and pregnancy; surveillance strategies for colitis-associated cancer; monitoring side effects of thiopurines and methotrexate; and infections in IBD.

Matched MeSH terms: Aminosalicylic Acid/adverse effects; Aminosalicylic Acid/therapeutic use
Fulltext Antimycobacterial, antimicrobial, and biocompatibility properties of para-aminosalicylic acid with zinc layered hydroxide and Zn/Al layered double hydroxide nanocomposites

Saifullah B, El Zowalaty ME, Arulselvan P, Fakurazi S, Webster TJ, Geilich BM, et al.

Drug Des Devel Ther, 2014;8:1029-36.
PMID: 25114509 DOI: 10.2147/DDDT.S63753

The treatment of tuberculosis by chemotherapy is complicated due to multiple drug prescriptions, long treatment duration, and adverse side effects. We report here for the first time an in vitro therapeutic effect of nanocomposites based on para-aminosalicylic acid with zinc layered hydroxide (PAS-ZLH) and zinc-aluminum layered double hydroxides (PAS-Zn/Al LDH), against mycobacteria, Gram-positive bacteria, and Gram-negative bacteria. The nanocomposites demonstrated good antimycobacterial activity and were found to be effective in killing Gram-positive and Gram-negative bacteria. A biocompatibility study revealed good biocompatibility of the PAS-ZLH nanocomposites against normal human MRC-5 lung cells. The para-aminosalicylic acid loading was quantified with high-performance liquid chromatography analysis. In summary, the present preliminary in vitro studies are highly encouraging for further in vivo studies of PAS-ZLH and PAS-Zn/Al LDH nanocomposites to treat tuberculosis.

Matched MeSH terms: Aminosalicylic Acid/chemistry*
Fulltext Development of a highly biocompatible antituberculosis nanodelivery formulation based on para-aminosalicylic acid-zinc layered hydroxide nanocomposites

Saifullah B, Arulselvan P, El Zowalaty ME, Fakurazi S, Webster TJ, Geilich B, et al.

ScientificWorldJournal, 2014;2014:401460.
PMID: 25050392 DOI: 10.1155/2014/401460

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.

Matched MeSH terms: Aminosalicylic Acid/chemistry*