| Reference | [1]. J Pharm Biomed Anal. 2019 Mar 20;166:371-378. doi: 10.1016/j.jpba.2019.01.037. Epub 2019 Jan 23.<br />
Electrospun nanofiber-based niflumic acid capsules with superior physicochemical properties.<br />
Radacsi N(1), Giapis KP(2), Ovari G(3), Szabó-Révész P(4), Ambrus R(4).<br />
Author information: (1)Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 E. California Blvd, Pasadena, CA, 91125, USA; Institute for Materials and Processes, The School of Engineering, The University of Edinburgh, Robert Stevenson Road, Edinburgh, EH9 3FB, UK. Electronic address: [email protected]. (2)Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 E. California Blvd, Pasadena, CA, 91125, USA. (3)Institute for Materials and Processes, The School of Engineering, The University of Edinburgh, Robert Stevenson Road, Edinburgh, EH9 3FB, UK. (4)Institute of Pharmaceutical Technology and Regulatory Affairs, University of Szeged, Interdisciplinary Excellence Centre, Eötvös Street 6, H-6720, Szeged, Hungary.<br />
The aim of this study was to assess whether nanofibrous drug mats have potential as delivery systems for poorly water-soluble drugs. Amorphous nanofiber mats from a model poorly water-soluble active pharmaceutical ingredient (API), niflumic acid, together with the polymer excipient, polyvinyl pyrrolidine, were prepared by nozzle-free electrospinning. This technique offers a scalable way for drug formulation, and by increasing the surface area of the drug, the dissolution rate and therefore bioavailability of the API can be improved. In this study, both the amount of the dissolved active ingredient and the dissolution kinetics has been improved significantly when the nanofibrous mats were used in the drug formulation. A 15-fold increase in the dissolved amount of the produced amorphous niflumic acid nanofiber was observed compared to the dissolved amount of the raw drug within the first 15 min. Capsule formulation was made by mixing the electrospun nanofibers with a microcrystalline cellulose filler agent. When comparing the dissolution rate of the capsule formulation on the market with the nanofibrous capsules, a 14-fold increase was observed in the dissolved drug amount within the first 15 min.<br />
DOI: 10.1016/j.jpba.2019.01.037 PMID: 30711806<br />
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[2]. Chin J Physiol. 2018 Dec 31;61(6):341-348. doi: 10.4077/CJP.2018.BAH635.<br />
Exploration of Niflumic Acid’s Action on Ca²⁺ Movement and Cell Viability in Human Osteosarcoma Cells.<br />
Liao WC(#)(1), Chou CT(2), Liang WZ(#)(3)(4), Hao LJ(#)(5), Kuo CC(6), Lin KL(7), Wang JL(7), Jan CR(3).<br />
Author information: (1)Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung 81362, Taiwan, Republic of China. (2)Department of Nursing, Division of Basic Medical Sciences, Chang Gung University of Science and Technology, Chia-Yi 61363, Taiwan, Republic of China. (3)Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung 81362, Taiwan, Republic of China. (4)Department of Pharmacy, Tajen University, Pingtung 90741, Taiwan, Republic of China. (5)Department of Metabolism, Kaohsiung Veterans General Hospital Tainan Branch, Tainan 71051, Taiwan, Republic of China. (6)Department of Nursing, Tzu Hui Institute of Technology, Pingtung 92641, Taiwan, Republic of China. (7)Department of Rehabilitation, Kaohsiung Veterans General Hospital, Kaohsiung 81362, Taiwan, Republic of China. (#)Contributed equally<br />
Niflumic acid, a drug used for joint and muscular pain, affected Ca²⁺ signaling in different models. However, the effect of niflumic acid on Ca²⁺ homeostasis and Ca²⁺-related physiology in human osteosarcoma cells is unknown. This study examined the effect of niflumic acid on cytosolic free Ca²⁺ concentrations ([Ca²⁺]i) in MG63 human osteosarcoma cells. Intracellular Ca²⁺ concentrations in suspended cells were monitored by using the fluorescent Ca²⁺-sensitive dye fura- 2. Cell viability was examined by using 4-[3-[4-lodophenyl]-2-4(4-nitrophenyl)-2H-5-tetrazolio- 1,3-benzene disulfonate] water soluble tetrazolium-1 (WST-1). In MG63 cells, niflumic acid at concentrations of 250-750 μM evoked [Ca²⁺]i rises concentration-dependently. Niflumic acid-evoked Ca²⁺ entry was confirmed by Mn²⁺-induced quenching of fura-2 fluorescence. This entry was inhibited by nifedipine, econazole, SKF96365, the protein kinase C (PKC) activator phorbol 12-myristate 13 acetate (PMA), but was not affected by the PKC inhibitor GF109203X. In Ca²⁺- free medium, treatment with the endoplasmic reticulum Ca²⁺ pump inhibitor thapsigargin (TG) inhibited niflumic acid-evoked [Ca²⁺]i rises. Conversely, treatment with niflumic acid abolished TG-evoked [Ca²⁺]i rises. Inhibition of phospholipase C (PLC) with U73122 also partly reduced niflumic acid-evoked [Ca²⁺]i rises. Niflumic acid killed cells at 200-500 μM in a concentration-dependent fashion. Chelating cytosolic Ca²⁺ with 1,2-bis(2-aminophenoxy)ethane-N,N,N’,N’-tetraacetic acid/ AM (BAPTA/AM) did not reverse niflumic acid-induced cytotoxicity. Collectively, our data suggest that in MG63 cells, niflumic acid induced [Ca²⁺]i rises by evoking PLC-dependent Ca²⁺ release from the endoplasmic reticulum, and Ca²⁺ entry via PKC-sensitive store-operated Ca²⁺ entry. Niflumic acid also induced Ca²⁺-independent cell death.<br />
DOI: 10.4077/CJP.2018.BAH635 PMID: 30580504<br />
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[3]. Reumatologia. 1975;13(3):227-32.<br />
[Niflumic acid].<br />
[Article in Polish]<br />
Danysz A.<br />
PMID: 1101331<br />
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[4]. Sci Rep. 2020 Aug 19;10(1):13999. doi: 10.1038/s41598-020-70983-2.<br />
Identification of the hypertension drug niflumic acid as a glycine receptor inhibitor.<br />
Ito D(1), Kawazoe Y(2), Sato A(3), Uesugi M(4), Hirata H(5).<br />
Author information: (1)Department of Chemistry and Biological Science, College of Science and Engineering, Aoyama Gakuin University, Sagamihara, 252-5258, Japan. (2)Saga University Center for Education and Research in Agricultural Innovation, Karatsu, 847-0021, Japan. (3)Institute of Transformative Bio-Molecules (WPI-ITbM), Nagoya University, Nagoya, 464-8601, Japan. (4)Institute for Chemical Research (ICR) and Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Uji, 611-0011, Japan. (5)Department of Chemistry and Biological Science, College of Science and Engineering, Aoyama Gakuin University, Sagamihara, 252-5258, Japan. [email protected].<br />
Glycine is one of the major neurotransmitters in the brainstem and the spinal cord. Glycine binds to and activates glycine receptors (GlyRs), increasing Cl- conductance at postsynaptic sites. This glycinergic synaptic transmission contributes to the generation of respiratory rhythm and motor patterns. Strychnine inhibits GlyR by binding to glycine-binding site, while picrotoxin blocks GlyR by binding to the channel pore. We have previously reported that bath application of strychnine to zebrafish embryos causes bilateral muscle contractions in response to tactile stimulation. To explore the drug-mediated inhibition of GlyRs, we screened a chemical library of ~ 1,000 approved drugs and pharmacologically active molecules by observing touch-evoked response of zebrafish embryos in the presence of drugs. We found that exposure of zebrafish embryos to nifedipine (an inhibitor of voltage-gated calcium channel) or niflumic acid (an inhibitor of cyclooxygenase 2) caused bilateral muscle contractions just like strychnine-treated embryos showed. We then assayed strychnine, picrotoxin, nifedipine, and niflumic acid for concentration-dependent inhibition of glycine-mediated currents of GlyRs in oocytes and calculated IC50s. The results indicate that all of them concentration-dependently inhibit GlyR in the order of strychnine > picrotoxin > nifedipine > niflumic acid.<br />
DOI: 10.1038/s41598-020-70983-2 PMCID: PMC7438329 PMID: 32814817<br />
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[5]. Inflammopharmacology. 2016 Dec;24(6):319-334. doi: 10.1007/s10787-016-0285-0. Epub 2016 Oct 18.<br />
Niflumic acid, a TRPV1 channel modulator, ameliorates stavudine-induced neuropathic pain.<br />
Marwaha L(1), Bansal Y(1), Singh R(1), Saroj P(1), Sodhi RK(1), Kuhad A(2).<br />
Author information: (1)Pharmacology Research Laboratory, University Institute of Pharmaceutical Sciences, UGC-Centre of Advanced Study, Punjab University, Chandigarh, 160 014, India. (2)Pharmacology Research Laboratory, University Institute of Pharmaceutical Sciences, UGC-Centre of Advanced Study, Punjab University, Chandigarh, 160 014, India. [email protected].<br />
TRP channels have been discovered as a specialized group of somatosensory neurons involved in the detection of noxious stimuli. Desensitization of TRPV1 located on dorsal root and trigeminal ganglia exhibits analgesic effect and makes it potential therapeutic target for treatment of neuropathic pain. With this background, the present study was aimed to investigate the protective effect of niflumic acid, a TRPV1 modulator, on stavudine (STV)-induced neuropathic pain in rats. Stavudine (50 mg/kg) was administered intravenously via tail vein in rats to induce neuropathic pain. Various behavioral tests were performed to access neuropathic pain (hyperalgesia and allodynia) on 7th, 14th, 21st, and 28th days. Electrophysiology (motor nerve conduction velocity; MNCV) and biochemical estimations were conducted after 28th day. Niflumic acid (10, 15, and 20 mg/kg) was administered intraperitoneally and evaluated against behavioral, electrophysiological (MNCV), and biochemical alterations in stavudine-treated rats. Pregabalin (30 mg/kg) was taken as reference standard and administered intraperitoneally. Four weeks after stavudine injection, rats developed behavioral, electrophysiological (MNCV), and biochemical (oxidative, nitrosative stress, and inflammatory cytokines, TRPV1) alterations. Niflumic acid restored core and associated symptoms of peripheral neuropathy by suppressing oxidative-nitrosative stress, inflammatory cytokines (TNF-α, IL-1β) and TRPV1 level in stavudine-induced neuropathic pain in rats. Pharmacological efficacy of niflumic acid (20 mg/kg) was equivalent to pregabalin (30 mg/kg). In conclusion, niflumic acid attenuates STV-induced behavioral, electrophysiological and biochemical alterations by manipulating TRP channel activity in two manners: (1) direct antagonistic action against TRPV1 channels and (2) indirect inhibition of TRP channels by blocking oxidative and inflammatory surge. Therefore, NA can be developed as a potential pharmacotherapeutic adjunct for antiretroviral drug-induced neuropathy.<br />
DOI: 10.1007/s10787-016-0285-0 PMID: 27757590
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