当前位置： SCI文献检索 > PHARMACEUTICAL RESEARCH期刊下所有文献 > Local Application of Pyrophosphorylated Simvastatin Prevents Experimental Periodontitis.

Local Application of Pyrophosphorylated Simvastatin Prevents Experimental Periodontitis.

Abstract：

PURPOSE:Simvastatin (SIM), a HMG-CoA reductase inhibitor widely prescribed for hypercholesterolemia, has been reported to ameliorate inflammation and promote osteogenesis. Its clinical applications on these potential secondary indications, however, have been hampered by its lack of osteotropicity and poor water solubility. To address this challenge, we propose to design and evaluate the therapeutic efficacy of a novel simvastatin prodrug with better water solubility and bone affinity. METHOD:The prodrug (SIM-PPi) was synthesized by directly conjugating a SIM trimer to a pyrophosphate (PPi). It was characterized and evaluated in vitro for its water solubility, osteotropicity, toxicity, anti-inflammatory and osteoinductive properties. It was then tested for anti-inflammatory and osteoinductive properties in vivo by three weekly injections into gingiva of a ligature-induced experimental periodontitis rat model. RESULTS:In vitro studies showed that SIM-PPi has greatly improved water-solubility of SIM and shows strong binding to hydroxyapatite (HA). In macrophage culture, SIM-PPi inhibited LPS-induced pro-inflammatory cytokines (IL-1β, IL-6). In osteoblast culture, it was found to significantly increase alkaline phosphatase (ALP) activity with accelerated mineral deposition, confirming the osteogenic potential of SIM-PPi. When tested in vivo on an experimental periodontal bone-loss model, SIM-PPi exhibited a superior prophylactic effect compared to dose equivalent SIM in reducing inflammatory cells and in preserving alveolar bone structure, as shown in the histological and micro-CT data. CONCLUSION:SIM-PPi may have the potential to be further developed for better clinical management of bone loss associated with periodontitis.

journal_name

Pharm Res

journal_title

Pharmaceutical research

authors

Wang X,Jia Z,Almoshari Y,Lele SM,Reinhardt RA,Wang D

doi

10.1007/s11095-018-2444-z

subject

Has Abstract

pub_date

2018-06-25 00:00:00

pages

164

issue

8

eissn

0724-8741

issn

1573-904X

pii

10.1007/s11095-018-2444-z

journal_volume

35

pub_type

杂志文章

相关文献

PHARMACEUTICAL RESEARCH文献大全
  • Asymmetric peptide dendrimers are effective linkers for antibody-mediated delivery of diverse payloads to b cells in vitro and in vivo.

    abstract：PURPOSE:Safe, targeted delivery of therapeutics remains a focus of drug/gene delivery, the aim being to achieve optimal efficacy while minimising off-target delivery. Dendrimers have a vast array of potential applications and have great potential as gene and drug delivery tools. We previously reported the development o...

    journal_title：Pharmaceutical research

    pub_type： 杂志文章

    doi：10.1007/s11095-014-1408-1

    authors： Shah ND,Parekh HS,Steptoe RJ

    更新日期：2014-11-01 00:00:00

  • Relationship among physicochemical properties, skin permeability, and topical activity of the racemic compound and pure enantiomers of a new antifungal.

    abstract：:The topical antifungal Sch-39304 is a racemic compound comprised of two enantiomers, Sch-42427 and Sch-42426, only one of which (Sch-42427) is pharmacologically active. The pure enantiomers have a lower melting point and, therefore, a higher solubility than the racemic compound. Because of these differences in physico...

    journal_title：Pharmaceutical research

    pub_type： 杂志文章

    doi：10.1023/a:1018945618264

    authors： Wearley L,Antonacci B,Cacciapuoti A,Assenza S,Chaudry I,Eckhart C,Levine N,Loebenberg D,Norris C,Parmegiani R

    更新日期：1993-01-01 00:00:00

  • Application of fractal kinetics for carrier-mediated transport of drugs across intestinal epithelial membrane.

    abstract：PURPOSE:Fractal kinetics was used for the analysis of the carrier-mediated transport for drugs across the intestinal epithelial cells. METHODS:The transport was examined under various agitation rates using a monolayer of Caco-2 cells and rabbit ileum sheets. RESULTS:The passive transport of antipyrine across Caco-2 c...

    journal_title：Pharmaceutical research

    pub_type： 杂志文章

    doi：10.1023/a:1011994230346

    authors： Ogihara T,Tamai I,Tsuji A

    更新日期：1998-04-01 00:00:00

  • Pectin and Mucin Enhance the Bioadhesion of Drug Loaded Nanofibrillated Cellulose Films.

    abstract：PURPOSE:Bioadhesion is an important property of biological membranes, that can be utilized in pharmaceutical and biomedical applications. In this study, we have fabricated mucoadhesive drug releasing films with bio-based, non-toxic and biodegradable polymers that do not require chemical modifications. METHODS:Nanofibr...

    journal_title：Pharmaceutical research

    pub_type： 杂志文章

    doi：10.1007/s11095-018-2428-z

    authors： Laurén P,Paukkonen H,Lipiäinen T,Dong Y,Oksanen T,Räikkönen H,Ehlers H,Laaksonen P,Yliperttula M,Laaksonen T

    更新日期：2018-05-22 00:00:00

  • Experimental and computational screening models for prediction of aqueous drug solubility.

    abstract：PURPOSE:To devise experimental and computational models to predict aqueous drug solubility. METHODS:A simple and reliable modification of the shake flask method to a small-scale format was devised, and the intrinsic solubilities of 17 structurally diverse drugs were determined. The experimental solubility data were us...

    journal_title：Pharmaceutical research

    pub_type： 杂志文章

    doi：10.1023/a:1014224900524

    authors： Bergström CA,Norinder U,Luthman K,Artursson P

    更新日期：2002-02-01 00:00:00

  • Influence of gallate esterification on the activity of procyanidin B2 in androgen-dependent human prostate carcinoma LNCaP cells.

    abstract：PURPOSE:Present study assessed the influence of gallate esterification on the anti-cancer activity of procyanidin B2 (B2) in androgen-dependent human prostate carcinoma LNCaP cells employing B2-3,3'-di-O-gallate (B2-G(2)), two mono-gallate esters B2-3-O-gallate (B2-3G) and B2-3'-O-gallate (B2-3'G) and the parent compou...

    journal_title：Pharmaceutical research

    pub_type： 杂志文章

    doi：10.1007/s11095-009-0037-6

    authors： Chou SC,Kaur M,Thompson JA,Agarwal R,Agarwal C

    更新日期：2010-04-01 00:00:00

  • Effects of Different Component Contents of Colistin Methanesulfonate on the Pharmacokinetics of Prodrug and Formed Colistin in Human.

    abstract：PURPOSES:To evaluate the effects of component contents in different colistin methanesulfonate (CMS) formulas on their clinical pharmacokinetics of the prodrug CMS and the formed colistin. METHODS:Two CMS formulas (CTTQ and Parkedale) were investigated in a single dose, randomized, open-label, crossover study conducted...

    journal_title：Pharmaceutical research

    pub_type： 杂志文章

    doi：10.1007/s11095-021-02991-4

    authors： Fan YX,Chen YC,Li Y,Yu JC,Bian XC,Li X,Li WZ,Guo BN,Wu HL,Liu XF,Wang Y,Xu XY,Hu JL,Wang JJ,Wu XJ,Cao GY,Wu JF,Xue CJ,Feng J,Zhang YY,Zhang J

    更新日期：2021-01-26 00:00:00

  • Role of Knowledge Management in Development and Lifecycle Management of Biopharmaceuticals.

    abstract：:Knowledge Management (KM) is a key enabler for achieving quality in a lifecycle approach for production of biopharmaceuticals. Due to the important role that it plays towards successful implementation of Quality by Design (QbD), an analysis of KM solutions is needed. This work provides a comprehensive review of the in...

    journal_title：Pharmaceutical research

    pub_type： 杂志文章,评审

    doi：10.1007/s11095-016-2043-9

    authors： Rathore AS,Garcia-Aponte OF,Golabgir A,Vallejo-Diaz BM,Herwig C

    更新日期：2017-02-01 00:00:00

  • Local Radiation Treatment of HER2-Positive Breast Cancer Using Trastuzumab-Modified Gold Nanoparticles Labeled with 177Lu.

    abstract：PURPOSE:To compare the effectiveness of trastuzumab-modified gold nanoparticles (AuNP) labeled with 177Lu (trastuzumab-AuNP-177Lu) targeted to HER2 with non-targeted AuNP-177Lu for killing HER2-overexpressing breast cancer (BC) cells in vitro and inhibiting tumor growth in vivo following intratumoral (i.t.) injection. ...

    journal_title：Pharmaceutical research

    pub_type： 杂志文章

    doi：10.1007/s11095-016-2082-2

    authors： Cai Z,Yook S,Lu Y,Bergstrom D,Winnik MA,Pignol JP,Reilly RM

    更新日期：2017-03-01 00:00:00

  • Mesoporous Silica Nanoparticle-Coated Microneedle Arrays for Intradermal Antigen Delivery.

    abstract：PURPOSE:To develop a new intradermal antigen delivery system by coating microneedle arrays with lipid bilayer-coated, antigen-loaded mesoporous silica nanoparticles (LB-MSN-OVA). METHODS:Synthesis of MSNs with 10-nm pores was performed and the nanoparticles were loaded with the model antigen ovalbumin (OVA), and coate...

    journal_title：Pharmaceutical research

    pub_type： 杂志文章

    doi：10.1007/s11095-017-2177-4

    authors： Tu J,Du G,Reza Nejadnik M,Mönkäre J,van der Maaden K,Bomans PHH,Sommerdijk NAJM,Slütter B,Jiskoot W,Bouwstra JA,Kros A

    更新日期：2017-08-01 00:00:00

  • Antigene, ribozyme and aptamer nucleic acid drugs: progress and prospects.

    abstract：:Nucleic acids are increasingly being considered for therapeutic uses, either to interfere with the function of specific nucleic acids or to bind specific proteins. Three types of nucleic acid drugs are discussed in this review: aptamers, compounds which bind specific proteins; triplex forming (antigene) compounds; whi...

    journal_title：Pharmaceutical research

    pub_type： 杂志文章,评审

    doi：10.1023/a:1016281324761

    authors： Stull RA,Szoka FC Jr

    更新日期：1995-04-01 00:00:00

  • Transfer of dopamine in the olfactory pathway following nasal administration in mice.

    abstract：PURPOSE:The aim of the study was to investigate whether dopamine is transferred along the olfactory pathway to the brain following nasal administration to mice. METHODS:[3H]-Dopamine was administered nasally or intravenously to female mice. Brain tissue samples were excised and the radioactive content was measured. Th...

    journal_title：Pharmaceutical research

    pub_type： 杂志文章

    doi：10.1023/a:1007542618378

    authors： Dahlin M,Bergman U,Jansson B,Björk E,Brittebo E

    更新日期：2000-06-01 00:00:00

  • Molecular mobility as a predictor of the water sorption by annealed amorphous trehalose.

    abstract：PURPOSE:The work aims at investigating the correlation of water sorption potential with different measures of molecular mobility in an annealed amorphous model compound (trehalose). METHODS:Amorphous trehalose, prepared by freeze-drying, was annealed at 100°C (17°C < T (g)) for up to 120 h. Global mo...

    journal_title：Pharmaceutical research

    pub_type： 杂志文章

    doi：10.1007/s11095-012-0910-6

    authors： Bhardwaj SP,Suryanarayanan R

    更新日期：2013-03-01 00:00:00

  • In vivo evaluation of enteric-coated naproxen tablets using gamma scintigraphy.

    abstract：:Seven healthy, male volunteers were entered into a randomized, open crossover study of the gastrointestinal transit of two enteric-coated 500-mg naproxen tablets. Two radiolabeled tablets were given to each volunteer on two occasions separated by 7 days, once in the fasted state and once after breakfast. Radiolabeling...

    journal_title：Pharmaceutical research

    pub_type： 临床试验,杂志文章,随机对照试验

    doi：10.1023/a:1015858829187

    authors： Wilding IR,Hardy JG,Sparrow RA,Davis SS,Daly PB,English JR

    更新日期：1992-11-01 00:00:00

  • Improved prediction of in vivo peroral absorption from in vitro intestinal permeability using an internal standard to control for intra- and inter-rat variability.

    abstract：PURPOSE:To evaluate the use of an in vitro intestinal permeability model to predict rat and human absorption as well as to evaluate the use of an internal standard to control for intra- and inter-rat variability. METHODS:In vivo peroral absorption and in vitro steady-state intestinal permeability coefficients were det...

    journal_title：Pharmaceutical research

    pub_type： 杂志文章

    doi：10.1023/a:1012148300807

    authors： Dowty ME,Dietsch CR

    更新日期：1997-12-01 00:00:00

  • Bioavailability prediction based on molecular structure for a diverse series of drugs.

    abstract：PURPOSE:Radial basis function artificial neural networks and theoretical descriptors were used to develop a quantitative structure-pharmacokinetic relationship for structurally diverse drug compounds. METHODS:Human bioavailability values were taken from the literature and descriptors were generated from the drug struc...

    journal_title：Pharmaceutical research

    pub_type： 杂志文章

    doi：10.1023/b:pham.0000012154.09631.26

    authors： Turner JV,Maddalena DJ,Agatonovic-Kustrin S

    更新日期：2004-01-01 00:00:00

  • Co-Delivery of Ciprofloxacin and Colistin in Liposomal Formulations with Enhanced In Vitro Antimicrobial Activities against Multidrug Resistant Pseudomonas aeruginosa.

    abstract：PURPOSE:This study aims to develop liposomal formulations containing synergistic antibiotics of colistin and ciprofloxacin for the treatment of infections caused by multidrug-resistant Pseudomonas aeruginosa. METHODS:Colistin (Col) and ciprofloxacin (Cip) were co-encapsulated in anionic liposomes by ammonium sulfate g...

    journal_title：Pharmaceutical research

    pub_type： 杂志文章

    doi：10.1007/s11095-018-2464-8

    authors： Wang S,Yu S,Lin Y,Zou P,Chai G,Yu HH,Wickremasinghe H,Shetty N,Ling J,Li J,Zhou QT

    更新日期：2018-08-09 00:00:00

  • The influence of cytotoxicity of macromolecules and of VEGF gene modulated vascular permeability on the enhanced permeability and retention effect in resistant solid tumors.

    abstract：PURPOSE:To study the influence of cytotoxicity of macromolecules, VEGF gene expression, and vascular permeability on the enhanced permeability and retention (EPR) effect. METHODS:Mice bearing xenografts of A2780 multidrug resistant human ovarian carcinoma were treated by free doxorubicin (DOX) and N-(2-hydroxypropyl)m...

    journal_title：Pharmaceutical research

    pub_type： 杂志文章

    doi：10.1023/a:1007500412442

    authors： Minko T,Kopeckova P,Pozharov V,Jensen KD,Kopecek J

    更新日期：2000-05-01 00:00:00

  • Hollow fibers as an oral sustained-release delivery system using propranolol hydrochloride.

    abstract：:Fibers were spun by the downward configuration of the wet spinning technique. This configuration is capable of encapsulating nonspherical and/or coarse particles. We examined encapsulation of propranolol hydrochloride and the ability of the fibers to act as a sustained-release delivery system for propranolol hydrochlo...

    journal_title：Pharmaceutical research

    pub_type： 杂志文章

    doi：10.1023/a:1015982521706

    authors： Hussain MA,DiLuccio RC,Shefter E,Hurwitz AR

    更新日期：1989-12-01 00:00:00

  • Selective effect of adjuvant arthritis on the disposition of propranolol enantiomers in rats detected using a stereospecific HPLC assay.

    abstract：:Nonstereospecific studies have indicated that the pharmacokinetics of propranolol (PR) are altered in inflammatory conditions such as arthritis. However, as the kinetics and dynamics of PR are stereoselective, we examined the effect of adjuvant arthritis (AA) on the disposition of the individual enantiomers. A novel n...

    journal_title：Pharmaceutical research

    pub_type： 杂志文章

    doi：10.1023/a:1018907431893

    authors： Piquette-Miller M,Jamali F

    更新日期：1993-02-01 00:00:00

  • Dextran-catechin conjugate: a potential treatment against the pancreatic ductal adenocarcinoma.

    abstract：PURPOSE:A polysaccharide-flavonoid conjugate was developend and proposed for the treatment of pancreatic ductal adenocarcinoma (PDAC). METHODS:The conjugate was synthesized by free radical grafting reaction between catechin and dextran. The chemical characterization of the conjugate was obtained by UV-Vis, 1H-NMR, FT-...

    journal_title：Pharmaceutical research

    pub_type： 杂志文章

    doi：10.1007/s11095-012-0790-9

    authors： Vittorio O,Cirillo G,Iemma F,Di Turi G,Jacchetti E,Curcio M,Barbuti S,Funel N,Parisi OI,Puoci F,Picci N

    更新日期：2012-09-01 00:00:00

  • Area/moment and compartmental modeling of pharmacokinetics during pregnancy: applications to maternal/fetal exposures to corticosteroids in sheep and rats.

    abstract：PURPOSE:The pharmacokinetics of corticosteroids in pregnancy were analyzed to assess maternal/fetal disposition and factors controlling fetal exposure. Area/Moment equations and compartmental models for estimating pharmacokinetic parameters from single dose data during pregnancy were developed. METHODS:Betamethasone i...

    journal_title：Pharmaceutical research

    pub_type： 杂志文章

    doi：10.1007/s11095-004-7681-7

    authors： Samtani MN,Schwab M,Nathanielsz PW,Jusko WJ

    更新日期：2004-12-01 00:00:00

  • The asymmetry of the unstirred water layer in permeability experiments.

    abstract：PURPOSE:To elucidate the apical and basolateral components of the total unstirred water layer in regular permeability experiment. METHODS:A novel stirring apparatus was constructed to remove the basolateral unstirred water layer. Caco-2 cells were used as the permeability barrier both in Transwell-type and side-by-sid...

    journal_title：Pharmaceutical research

    pub_type： 杂志文章

    doi：10.1007/s11095-008-9573-8

    authors： Korjamo T,Heikkinen AT,Waltari P,Mönkkönen J

    更新日期：2008-07-01 00:00:00

  • Buccal absorption. III. Simultaneous diffusion and metabolism of an aminopeptidase substrate in the hamster cheek pouch.

    abstract：:The simultaneous diffusion and metabolism of the D- and L-isomers of the aminopeptidase substrate, leucine-p-nitroanilide (LPNA), were examined in vitro in the hamster cheek pouch. L-LPNA was completely hydrolyzed during diffusion across the cheek pouch, whereas D-LPNA crossed the cheek pouch intact. The metabolic bar...

    journal_title：Pharmaceutical research

    pub_type： 杂志文章

    doi：10.1023/a:1015949614437

    authors： Garren KW,Topp EM,Repta AJ

    更新日期：1989-11-01 00:00:00

  • Transport characteristics of peptidomimetics. Effect of the pyrrolinone bioisostere on transport across Caco-2 cell monolayers.

    abstract：PURPOSE:To compare the permeation characteristics of amide bond-containing HIV-1 protease inhibitors and their pyrrolinone-containing counterparts across Caco-2 cell monolayers, a model of the intestinal mucosa. METHODS:Transepithelial transport and cellular uptake of three pairs of amide bond-containing and pyrrolino...

    journal_title：Pharmaceutical research

    pub_type： 杂志文章

    doi：10.1023/a:1011966918959

    authors： Sudoh M,Pauletti GM,Yao W,Moser W,Yokoyama A,Pasternak A,Sprengeler PA,Smith AB 3rd,Hirschmann R,Borchardt RT

    更新日期：1998-05-01 00:00:00

  • Characterization of the transport properties of a quinolone antibiotic, fleroxacin, in rat choroid plexus.

    abstract：PURPOSE:It is reported that the cerebrospinal fluid (CSF) to plasma unbound concentration ratio of fleroxacin at steady-state is approximately 0.5 in experimental animals. These results can be accounted for by assuming the presence of an active transport system for the efflux of this compound across the choroid plexus....

    journal_title：Pharmaceutical research

    pub_type： 杂志文章

    doi：10.1023/a:1016081618149

    authors： Ooie T,Suzuki H,Terasaki T,Sugiyama Y

    更新日期：1996-04-01 00:00:00

  • Evidence for LHRH-receptor expression in human airway epithelial (Calu-3) cells and its role in the transport of an LHRH agonist.

    abstract：PURPOSE:To determine whether LHRH-receptor is expressed in Calu-3, a human bronchial epithelial cell line, and to further determine whether this receptor plays a role in the transport of deslorelin, an LHRH agonist. METHODS:Using cultured monolayers of Calu-3 grown at air-interface, the presence and localization of LH...

    journal_title：Pharmaceutical research

    pub_type： 杂志文章

    doi：10.1023/b:pham.0000029294.70707.74

    authors： Koushik K,Bandi N,Sundaram S,Kompella UB

    更新日期：2004-06-01 00:00:00

  • Nanoparticulate Impurities in Pharmaceutical-Grade Sugars and their Interference with Light Scattering-Based Analysis of Protein Formulations.

    abstract：PURPOSE:In the present study we investigated the root-cause of an interference signal (100-200 nm) of sugar-containing solutions in dynamic light scattering (DLS) and nanoparticle tracking analysis (NTA) and its consequences for the analysis of particles in biopharmaceutical drug products. METHODS:Different sugars as ...

    journal_title：Pharmaceutical research

    pub_type： 杂志文章

    doi：10.1007/s11095-015-1634-1

    authors： Weinbuch D,Cheung JK,Ketelaars J,Filipe V,Hawe A,den Engelsman J,Jiskoot W

    更新日期：2015-07-01 00:00:00

  • Percutaneous penetration enhancement in vivo measured by attenuated total reflectance infrared spectroscopy.

    abstract：:A novel application of attenuated total reflectance IR spectroscopy (ATR-IR) was used to monitor the outer several microns of the stratum corneum (SC) and, thereby, demonstrate enhanced percutaneous absorption in vivo in man. 4-Cyanophenol (CP) as a model permeant yielded a unique IR signal, distinct from those of the...

    journal_title：Pharmaceutical research

    pub_type： 杂志文章

    doi：10.1023/a:1015960815578

    authors： Mak VH,Potts RO,Guy RH

    更新日期：1990-08-01 00:00:00

  • Modeling of corticosteroid effects on hepatic low-density lipoprotein receptors and plasma lipid dynamics in rats.

    abstract：PURPOSE:This study examines methylprednisolone (MPL) effects on the dynamics of hepatic low-density lipoprotein receptor (LDLR) mRNA and plasma lipids associated with increased risks for atherosclerosis. MATERIALS AND METHODS:Normal male Wistar rats were given 50 mg/kg MPL intramuscularly (IM) and sacrificed at variou...

    journal_title：Pharmaceutical research

    pub_type： 杂志文章

    doi：10.1007/s11095-007-9371-8

    authors： Hazra A,Pyszczynski NA,DuBois DC,Almon RR,Jusko WJ

    更新日期：2008-04-01 00:00:00