| Reference | [1]. J Drug Target. 2019 Nov;27(9):984-994. doi: 10.1080/1061186X.2019.1574300. Epub 2019 Feb 11.<br />
Anti-inflammatory flurbiprofen nasal powders for nose-to-brain delivery in Alzheimer's disease.<br />
Tiozzo Fasiolo L(1)(2), Manniello MD(3), Bortolotti F(2), Buttini F(1), Rossi A(1), Sonvico F(1), Colombo P(1)(4), Valsami G(5), Colombo G(2), Russo P(3).<br />
Author information: (1)a Department of Food and Drug, University of Parma , Parma , Italy. (2)b Department of Life Sciences and Biotechnology, University of Ferrara , Ferrara , Italy. (3)c Department of Pharmacy, University of Salerno , Fisciano (SA) , Italy. (4)d PlumeStars Srl , Parma , Italy. (5)e Department of Pharmacy, National and Kapodistrian University of Athens , Athens , Greece.<br />
Neuroinflammation occurs in the early stages of Alzheimer's disease (AD). Thus, anti-inflammatory drugs in this asymptomatic initial phase could slow down AD progression, provided they enter the brain. Direct nose-to-brain drug transport occurs along olfactory or trigeminal nerves, bypassing the blood-brain barrier. Nasal administration may enable the drug to access the brain. Here, flurbiprofen powders for nose-to-brain drug transport in early AD-related neuroinflammation were studied. Their target product profile contemplates drug powder deposition in the nasal cavity, prompt dissolution in the mucosal fluid and attainment of saturation concentration to maximise diffusion in the tissue. Aiming to increase drug disposition into brain, poorly soluble flurbiprofen requires the construction of nasal powder microparticles actively deposited in nose for prompt drug release. Two groups of powders were formulated, composed of flurbiprofen acid or flurbiprofen sodium salt. Two spray dryer apparatuses, differing for spray and drying mechanisms, and particle collection, were applied to impact on the characteristics of the microparticulate powders. Flurbiprofen sodium nasal powders disclosed prompt dissolution and fast ex vivo transport across rabbit nasal mucosa, superior to the acid form, in particular when the powder was prepared using the Nano B-90 spray dryer at the lowest drying air temperature.<br />
DOI: 10.1080/1061186X.2019.1574300 PMID: 30691325 [Indexed for MEDLINE]<br />
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[2]. J Arthroplasty. 2020 Aug;35(8):2033-2038. doi: 10.1016/j.arth.2020.04.006. Epub 2020 Apr 10.<br />
Effect of Flurbiprofen and S-Flurbiprofen Patches on Multimodal Pain Management After Total Knee Arthroplasty: A Prospective Randomized Controlled Trial.<br />
Tsuji M(1), Kobayashi N(1), Yukizawa Y(1), Oishi T(1), Takagawa S(1), Inaba Y(2).<br />
Author information: (1)Department of Orthopaedic Surgery, Yokohama City University Medical Center, Yokohama, Japan. (2)Department of Orthopaedic Surgery, Yokohama City University School of Medicine, Yokohama, Japan.<br />
BACKGROUND: Total knee arthroplasty (TKA) is an established procedure for knee osteoarthritis. Multimodal analgesia is reportedly more effective for postoperative analgesia. We investigated the efficacy of 2 patches after TKA. METHODS: Seventy-nine knees that underwent unilateral TKA for osteoarthritis were included. Oral administration, local periarticular analgesic injection, and patches were adopted for pain management. The knees were randomly assigned to the flurbiprofen patch (FPP), S-flurbiprofen patch (SFPP), and control (no patch) groups. Patch treatment was continued for 14 days. Pain according to the visual analog scale, knee flexion angle, renal dysfunction, gastrointestinal injury, duration of hospitalization, dermatitis, and the rate of using additional oral nonsteroidal anti-inflammatory drugs were compared (from preoperative to postoperative day 14). RESULTS: The FPP, SFPP, and control groups included 29, 27, and 23 knees, respectively. Visual analog scale was lower in the FPP and SFPP groups than in the control group on days 1 and 3 (day 1: 24.4, 25.0, and 39.4, respectively; day 3: 25.5, 23.3, and 39.3, respectively). Knee flexion angle was larger in the SFPP group than in the control group on days 7 and 14 (day 7: 89.8° and 76.6°, respectively; day 14: 98.3° and 84.2°, respectively). Neither renal dysfunction nor gastrointestinal injury was confirmed. The duration of hospitalization did not differ among the groups. Dermatitis occurred only in the SFPP group. The rate of using additional oral nonsteroidal anti-inflammatory drugs was higher in the control group. CONCLUSION: Both patches were effective and safe as part of multimodal analgesia for postoperative TKA.<br />
DOI: 10.1016/j.arth.2020.04.006 PMID: 32362479 [Indexed for MEDLINE]<br />
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[3]. Chem Res Toxicol. 2019 Aug 19;32(8):1504-1514. doi: 10.1021/acs.chemrestox.8b00404. Epub 2019 Jul 8.<br />
Flurbiprofen Inhibits Androgen Productions in Rat Immature Leydig Cells.<br />
Wang Y(1), Zheng W(1), Shan Y(2), Qiu L(3), Dong Y(2), Ni C(1), Li X(1), Huang T(1), Zhu Q(1), Lian Q(1), Ge RS(1).<br />
Author information: (1)Department of Anesthesiology , The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University , Wenzhou , Zhejiang 325027 , People's Republic of China. (2)Department of Pathology , The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University , Wenzhou , Zhejiang 325035 , People's Republic of China. (3)Department of Anesthesiology , The Affiliated Hospital of Guiyang Medical University , Guiyang , Guizhou 550001 , People's Republic of China.<br />
Flurbiprofen is one of the nonsteroidal anti-inflammatory drugs. Whether flurbiprofen affects androgen biosynthesis in Leydig cells is still unknown. Immature Leydig cells (ILCs) isolated from 35-day-old male Sprague-Dawley rats were cultured with 0-100 μM flurbiprofen for 24 h and medium androgen levels and Leydig cell mRNA levels were measured. Immature Leydig cells were also incubated with 100 μM flurbiprofen for 3 h in combination with luteinizing hormone (LH), 8bromo-cAMP, 22R-OH-cholesterol, pregnenolone, progesterone, androstenedione, testosterone, and dihydrotestosterone, respectively, and medium androgen levels were measured. The ROS generation and apoptosis rate were also investigated. The direct effects of flurbiprofen on androgen biosynthetic and metabolizing enzyme activities were measured. Flurbiprofen significantly inhibited basal, LH, and 8bromo-cAMP stimulated androgen production at 10 and 100 μM. Further study demonstrated that flurbiprofen competitively inhibited rat and human testis 3β-hydroxysteroid dehydrogenase (HSD3B) activity with the half maximal inhibitory concentration (IC50) values of 0.95 μM for rat enzyme and 6.31 μM for human enzyme. In addition, flurbiprofen down-regulated the expression of Srd5a1 and Akr1c14 at 1, 10, and 100 μM. Flurbiprofen also down-regulated Lhcgr expression at 100 μM. Flurbiprofen at 10 and 100 μM increased ROS production and apoptosis rate of rat Leydig cells. In conclusion, flurbiprofen directly inhibits HSD3B activity and the expression levels of Srd5a1 and Akr1c14 in rat Leydig cells, thus leading to the reduction of androgen secretion.<br />
DOI: 10.1021/acs.chemrestox.8b00404 PMID: 31184881 [Indexed for MEDLINE]<br />
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[4]. Chirality. 2019 Jun;31(6):457-467. doi: 10.1002/chir.23071. Epub 2019 May 7.<br />
Enantioseparation of flurbiprofen enantiomers using chiral ionic liquids by liquid-liquid extraction.<br />
Cui X(1)(2), Ding Q(1)(2), Shan RN(1)(2), He CH(1)(2), Wu KJ(3).<br />
Author information: (1)Zhejiang Provincial Key Laboratory of Advanced Chemical Engineering Manufacture Technology, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, China. (2)Institute of Zhejiang University-Quzhou, Quzhou, China. (3)School of Chemical and Process Engineering, University of Leeds, Leeds, UK.<br />
Flurbiprofen is a kind of nonsteroidal anti-inflammatory drug, which has been widely used in clinic for treatment of rheumatoid arthritis and osteoarthritis. It has been reported that S-flurbiprofen shows good performance on clinic anti-inflammatory treatment, while R-enantiomer almost has no pharmacological activities. It has important practical values to obtain optically pure S-flurbiprofen. In this work, chiral ionic liquids, which have good structural designability and chiral recognize ability, were selected as the extraction selector by the assistance of quantum chemistry calculations. The distribution behaviors of flurbiprofen enantiomers were investigated in the extraction system, which was composed of organic solvent and aqueous phase containing chiral ionic liquid. The results show that maximum enantioselectivity up to 1.20 was attained at pH 2.0, 25°C using 1,2-dichloroethane as organic solvent, 1-butyl-3-methylimidazole L-tryptophan ([Bmim][L-trp]) as chiral selector. The racemic flurbiprofen initial concentration was 0.2 mmol L-1 , and [Bmim][L-trp] concentration was 0.02 mol L-1 . Furthermore, the recycle of chiral ionic liquids has been achieved by reverse extraction process of the aqueous phase with chiral selector, which is significant for industrial application of chiral ionic liquids and scale-up of the extraction process.<br />
DOI: 10.1002/chir.23071 PMID: 31062890 [Indexed for MEDLINE]<br />
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[5]. J Pharm Pharmacol. 2018 Jul;70(7):929-936. doi: 10.1111/jphp.12914. Epub 2018 Apr 1.<br />
Analgesic effect of S (+)-flurbiprofen plaster in a rat model of knee arthritis: analysis of gait and synovial fluid prostaglandin E(2) levels.<br />
Fukumoto A(1), Tajima K(1), Hori M(1), Toda Y(2), Kaku S(1), Matsumoto H(3).<br />
Author information: (1)Pharmacology Laboratories, Taisho Pharmaceutical Co., Ltd., Saitama, Japan. (2)Pharmaceutical Business Strategic Planning, Taisho Pharmaceutical Co., Ltd., Tokyo, Japan. (3)Institute for Integrated Sports Medicine, Keio University School of Medicine, Tokyo, Japan.<br />
OBJECTIVES: We developed S (+)-flurbiprofen plaster (SFPP), a novel NSAID patch containing S (+)-flurbiprofen (SFP), a potent cyclooxygenase (COX) inhibitor. The purpose of this study was to assess efficacy of SFPP by analysing its effect on the gait disturbance and measuring the prostaglandin E2 (PGE2 ) production in synovial fluid in a rat model of knee arthritis. METHODS: Knee inflammation was induced in rats by intra-articular injection of a yeast suspension. Subsequently, an NSAID patch containing SFP, ketoprofen or loxoprofen was applied over the affected knee. Gait was assessed at 2, 4 and 6 h after application of the patch. The PGE2 concentration in the synovial fluid was measured after the gait assessment. KEY FINDINGS: Application of SFPP (0.125, 0.25, 0.5 or 1 mg/sheet) was followed by a decrease in the visual gait score at all the doses examined. In the case of the other two NSAID patches, only the ketoprofen patch (1 or 2 mg/sheet) and loxoprofen patch (5 mg/sheet) produced a decrease in the visual gait score. All of the NSAID patches decreased the PGE2 production in the synovial fluid. CONCLUSIONS: These results suggest the potential usefulness of SFPP as an analgesic patch in patients with inflammatory joint pain.<br />
DOI: 10.1111/jphp.12914 PMCID: PMC6033094 PMID: 29607510 [Indexed for MEDLINE]
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