Synthesis and characterization of pH tolerant and mucoadhesive (thiol-polyethylene glycol) chitosan graft polymer for drug delivery.

Abstract:

:The objective of this study was to generate a water-soluble thiolated chitosan to enable the permeation-enhancing effect of chitosan at pH of at least 5.5 without losing the advantages of improved mucoadhesive properties. Therefore, the thiol-bearing polyoxyethylene ligand {O-(3-carboxylpropyl)-O'-[2-[3-mercaptopropionylamino)ethyl]-polyethyleneglycol} was conjugated via amide bond formation to the amino group of chitosan. Resulting novel chitosan derivative (Chito-PEG-SH) exhibited 250 μmol free thiol groups per gram polymer. By the attachment of the thiol-bearing PEG ligand, an improvement of permeation-enhancing effect on rat intestine (2.7-fold improvement) as well as on a Caco-2 monolayer model (1.9-fold improvement) could be found. Cytotoxicity studies on Caco-2 cells revealed no change in biocompatibility. Mucoadhesion was improved 3.1-fold by the formation of disulfide bonds with mucus glycoproteins. The mucoadhesive effect of Chito-PEG-SH turned out to be similar to thiolated chitosan and more pronounced than mucoadhesive properties of unmodified chitosan. The graft polymer is soluble in water and aqueous solutions over a broad pH range. In aqueous media, the novel polymer does not precipitate at pH of 8.6 or less. According to these results, Chito-PEG-SH might show potential as auxiliary agent in oral drug delivery where its solubility even up to pH 8 is likely beneficial.

journal_name

J Pharm Sci

authors

Hauptstein S,Bonengel S,Griessinger J,Bernkop-Schnürch A

doi

10.1002/jps.23832

subject

Has Abstract

pub_date

2014-02-01 00:00:00

pages

594-601

issue

2

eissn

0022-3549

issn

1520-6017

pii

S0022-3549(15)30726-7

journal_volume

103

pub_type

杂志文章
  • Reevaluation of the absorption of carbenoxolone using an in situ rat intestinal technique.

    abstract::The absorption of the model drug carbenoxolone was reevaluated using an in situ rat intestinal perfusion technique in which disappearance from the intestinal lumen, binding to the perfused jejunal segment, and appearance in the mesenteric (jejunal) vein were measured. The effect of the degree of ionization on these pr...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.2600790510

    authors: Blanchard J,Tang LM,Earle ME

    更新日期:1990-05-01 00:00:00

  • Distribution and elimination of polymethyl methacrylate nanoparticles after peroral administration to rats.

    abstract::Polymethyl [1-14C]methacrylate nanoparticles were administered orally to bile cannulated rats. Ten to fifteen percent of the administered radioactivity was absorbed and found in the bile and urine. Within 48 h, 94-97% of the absorbed radioactivity had been eliminated from the body. After 8 d, the highest residual radi...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.2600730934

    authors: Nefzger M,Kreuter J,Voges R,Liehl E,Czok R

    更新日期:1984-09-01 00:00:00

  • Intravascular bioresorbable polymeric stents: a potential alternative to current drug eluting metal stents.

    abstract::Stent implantation following angioplasty is the standard treatment of coronary artery disease necessitating interventional procedures. The use of stents as a platform for local drug delivery is a popular strategy to achieve local pharmacological treatment to the diseased artery. Drug eluting stents (DES) are now large...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章,评审

    doi:10.1002/jps.20957

    authors: Sharkawi T,Cornhill F,Lafont A,Sabaria P,Vert M

    更新日期:2007-11-01 00:00:00

  • Investigating monoclonal antibody aggregation using a combination of H/DX-MS and other biophysical measurements.

    abstract::To determine how structural changes in antibodies are connected with aggregation, the structural areas of an antibody prone to and/or impacted by aggregation must be identified. In this work, the higher-order structure and biophysical properties of two different monoclonal antibody (mAb) monomers were compared with th...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.23754

    authors: Iacob RE,Bou-Assaf GM,Makowski L,Engen JR,Berkowitz SA,Houde D

    更新日期:2013-12-01 00:00:00

  • Kinetic and mechanistic studies of blue tetrazolium reaction with phenylhydrazines.

    abstract::The reaction kinetics of blue tetrazolium with selected arylhydrazines were investigated under pseudo-first-order conditions. The reaction rate constants were obtained at various temperatures, and the enthalpy (8.4-11.2 kcal/mole) and entropy (-38--45 eu) of activations were calculated. A Hammett plot yielded a straig...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.2600670714

    authors: Biehl ER,Wooten R,Kenner CT,Graham RE

    更新日期:1978-07-01 00:00:00

  • Stabilization and HPLC analysis of betamethasone sodium phosphate in plasma.

    abstract::The analysis of corticosteroid prodrugs in pharmacokinetic (PK) studies poses the risk of overestimation of corticosteroid concentrations due to in vitro hydrolysis of prodrugs after sample collection. This study tests the effectiveness of enzyme inhibitors as stabilizers for betamethasone sodium phosphate (BSP) in pr...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.10577

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

    更新日期:2004-03-01 00:00:00

  • A novel approach to preparing water soluble prodrug forms of cisplatin analogues bearing chelating diamines.

    abstract::A novel method for creating water soluble prodrugs of cisplatin analogues bearing chelating diamines is introduced. When 2-(amino-methyl)aniline is reacted with K2PtCl4 between a pH of 6 and 7, the neutral chelated complex [2-(aminomethyl)aniline)dichloroplatinum(II) (1) is isolated. On the other hand, when the comple...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.2600840707

    authors: Köckerbauer R,Bednarski PJ

    更新日期:1995-07-01 00:00:00

  • Fluorescence assay of nitrofurantoin with o-aminothiophenol in plasma and urine.

    abstract::A fluorescence method is presented for the determination of nitrofurantoin based on conversion of the drug to a fluorescent substance. The method requires 0.1-0.5 ml of plasma or diluted urine and is 10 times more sensitive than the commonly used colorimetric method. ...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.2600690134

    authors: Watari N,Funaki T,Kaneniwa N

    更新日期:1980-01-01 00:00:00

  • Utilizing a novel tandem oral dosing strategy to enhance exposure of low-solubility drug candidates in a preclinical setting.

    abstract::Time and resource constraints necessitate increasingly early decision making to accelerate or stop preclinical drug discovery programs. Early discovery drug candidates may be potent inhibitors of new targets, but all too often exhibit poor pharmaceutical and pharmacokinetic properties that limit the in vivo exposure. ...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.22092

    authors: Chiang PC,South SA,Foster KA,Daniels JS,Wene SP,Albin LA,Thompson DC

    更新日期:2010-07-01 00:00:00

  • Attaching zanamivir to a polymer markedly enhances its activity against drug-resistant strains of influenza a virus.

    abstract::Effects of the commercial drug zanamivir (Relenza) covalently attached to poly-l-glutamine on the infectivity of influenza A viruses are examined using the plaque reduction assay and binding affinity to viral neuraminidase (NA). These multivalent drug conjugates exhibit (i) up to a 20,000-fold improvement in anti-infl...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.22338

    authors: Weight AK,Haldar J,Alvarez de Cienfuegos L,Gubareva LV,Tumpey TM,Chen J,Klibanov AM

    更新日期:2011-03-01 00:00:00

  • Impact of curcumin supersaturation in antibacterial photodynamic therapy--effect of cyclodextrin type and amount: studies on curcumin and curcuminoides XLV.

    abstract::Curcumin has been investigated as a potential photosensitizer (PS) in antimicrobial photodynamic therapy (aPDT). The phototoxic effect of curcumin is dependent on proper formulations of the compound because of the lipophilic nature of the molecule and the extremely low water solubility at physiological conditions. In ...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.23046

    authors: Hegge AB,Nielsen TT,Larsen KL,Bruzell E,Tønnesen HH

    更新日期:2012-04-01 00:00:00

  • Segmental difference and effect of glucose on drug exsorption across the small intestine of rats.

    abstract::An exsorption technique which can assess the transport of a drug from blood to the intestinal lumen was used to study the effects of glucose and to determine the presence of segmental differences in drug transport across the rat small intestinal membrane following intravenous drug administration. The drugs used in the...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.2600740319

    authors: Johno I,Kitazawa S

    更新日期:1985-03-01 00:00:00

  • Enzyme inhibition. VIII: Mode of inhibition of reverse transcriptase activity by analogues, isomers, and related alkaloids of coralyne.

    abstract::Coralyne analogues, isomers, and related alkaloids were examined as inhibitors of reverse transcriptase of RNA tumor viruses in the presence of polyriboadenylic acid-oligodeoxythymidylic acid (Poly rA.oligo dT), polydeoxyadenylic acid-oligodeoxythymidylic acid (Poly dA.oligo dT), polyribocytidylic acid-oligodeoxyguany...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.2600740819

    authors: Sethi ML

    更新日期:1985-08-01 00:00:00

  • Transformation of 2,2'-anhydro-1-beta-D-arabinofuranosylcytosine induced by hydrogen peroxide.

    abstract::2,2'-Anhydro-1-beta-D-arabinofuranosylcytosine (I) is a more potent and less toxic antineoplastic agent than is cytarabine (1-beta-D-arabinofuranosylcytosine) (II). The anhydronucleoside (I) was found to be readily transformed by hydrogen peroxide into 2,2'-anhydro-5-hydroxy-1-beta-D-arabinofuranosylcytosine (III) by ...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.2600640315

    authors: Kikugawa K

    更新日期:1975-03-01 00:00:00

  • Alloxan analogues as potential pancreatic-imaging radiopharmaceuticals.

    abstract::Three families of alloxan derivatives, 5-arylthiobarbituric, 5-aryliminobarbituric, and 5-aryldialuric acids, were prepared as prospective radioiodine-transporting radiopharmaceuticals for the delineation of pancreatic insulinomas. Members of each class were screened for effects on blood sugar levels in a rat glucose ...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.2600730327

    authors: Adams WE,Heindel ND,Tutwiler G,Fawthrop H

    更新日期:1984-03-01 00:00:00

  • GLC-mass spectrometry of Teucrium polium oil.

    abstract::The essential oil of Teucrium polium, growing in Saudi Arabia, was thoroughly investigated for its constituents by GLC-mass spectrometry, TLC, and spectrophotometric methods. This investigation revealed the presence of 10 terpenoidal compounds including the hydrocarbons beta-pinene, limonene, alpha-phellandrene, and g...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.2600680639

    authors: Hassan MM,Muhtadi FJ,Al-Badr AA

    更新日期:1979-06-01 00:00:00

  • Determination of free bile acids in pharmaceutical preparations by packed column supercritical fluid chromatography.

    abstract::A method was developed for the baseline separation of common free bile acids by supercritical fluid chromatography. A phenylbonded silica column, with UV detection at 210 nm, and carbon dioxide modified with methanol as the mobile phase were used. The influence of the stationary phase, modifier concentration, temperat...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.2600820110

    authors: Scalia S,Games DE

    更新日期:1993-01-01 00:00:00

  • Preparation of in situ-forming ophthalmic gels of ciprofloxacin hydrochloride for the treatment of bacterial conjunctivitis: in vitro and in vivo studies.

    abstract::Sol-to-gel systems of ciprofloxacin hydrochloride were prepared utilizing the phase transition properties of hydroxy propyl methyl cellulose K 15 M grade (HPMC) and carbopol 934. The sol-to-gel systems were sterilized by gamma radiation and/or filtration. The sol-to-gel systems were evaluated for rheological character...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.10290

    authors: Charoo NA,Kohli K,Ali A

    更新日期:2003-02-01 00:00:00

  • Determination of mianserin and metabolites in plasma by liquid chromatography with electrochemical detection.

    abstract::A procedure for the determination of mianserin, desmethylmianserin, and 8-hydroxymianserin in plasma at therapeutic concentrations by liquid chromatography with electrochemical detection is described. Following a multiple-step extraction from alkaline plasma into methyl-tert-butyl ether, the reconstituted extract was ...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.2600710812

    authors: Suckow RF,Cooper TB,Quitkin FM,Stewart JW

    更新日期:1982-08-01 00:00:00

  • Differential elimination of synthetic butyric triglycerides in vivo: a pharmacokinetic study.

    abstract::New butyrate derivatives were synthesized to investigate the residence time of potent butyric acid in vivo. These derivatives were triglycerides in which one, two, or three butyric acid molecules were bound to glycerol or to mono- and dipalmitic esters of glycerol. Pharmacokinetic studies showed that a constant plasma...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:

    authors: Planchon P,Pouillart P,Ronco G,Villa P,Pieri F

    更新日期:1993-10-01 00:00:00

  • Synthesis, stability, and pharmacological evaluation of nipecotic acid prodrugs.

    abstract::Nipecotic acid (1), one of the most potent in vitro inhibitors of neuronal and glial gamma-amino butyric acid (GABA) uptake, is inactive as an anticonvulsant when administered systemically. To obtain in vivo active prodrugs of (1), we synthesized four new nipecotic acid esters (3-6), which were obtained by chemical co...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1021/js980302n

    authors: Bonina FP,Arenare L,Palagiano F,Saija A,Nava F,Trombetta D,de Caprariis P

    更新日期:1999-05-01 00:00:00

  • Improvement in solubility and dissolution rate of 1, 2-dithiole-3-thiones upon complexation with beta-cyclodextrin and its hydroxypropyl and sulfobutyl ether-7 derivatives.

    abstract::Inclusion complexes between beta-cyclodextrin derivatives and 1, 2-dithione-3-thiones were studied in aqueous solution and in the solid state. Phase solubility study was used to evaluate the complexation in solution, at 37 degrees C, of three cyclodextrins, i. e., beta-cyclodextrin (betaCD), hydroxypropyl-beta-cyclode...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1021/js990067o

    authors: Dollo G,Le Corre P,Chollet M,Chevanne F,Bertault M,Burgot JL,Le Verge R

    更新日期:1999-09-01 00:00:00

  • Chloride ion nuclear magnetic resonance spectroscopy probe studies of copper and nickel binding to serum albumins.

    abstract::The binding of Cu2+ and Ni2+ to bovine, dog, and human serum albumin has been studied by the 35Cl NMR probe technique. The number of primary copper sites were estimated to be 1.3 for human serum albumin, 3.1 for bovine serum albumin, and 6.6 for dog serum albumin. A similar number of primary nickel sites was determine...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.2600740116

    authors: Mohanakrishnan P,Chignell CF,Cox RH

    更新日期:1985-01-01 00:00:00

  • Controlled and complete release of a model poorly water-soluble drug, prednisolone, from hydroxypropyl methylcellulose matrix tablets using (SBE)(7m)-beta-cyclodextrin as a solubilizing agent.

    abstract::Sustained-release formulations such as hydroxypropyl methylcellulose (HPMC)-based hydrophilic matrix tablets of poorly water-soluble drugs often result in incomplete release because of the poor solubility and dissolution rate of the drug in the hydrophilic matrix. Sulfobutylether-beta-cyclodextrins ((SBE)(7M)-beta-CDs...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.1034

    authors: Rao VM,Haslam JL,Stella VJ

    更新日期:2001-07-01 00:00:00

  • Fcγ Receptor Activation by Human Monoclonal Antibody Aggregates.

    abstract::Protein aggregates are a potential risk factor for immunogenicity. The measurement, characterization, and control of protein aggregates in drug products are indispensable for the development of biopharmaceuticals, including therapeutic mAbs. In this study, Fcγ receptor (FcγR)-expressing reporter cell lines were used t...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1016/j.xphs.2019.10.046

    authors: Tada M,Aoyama M,Ishii-Watabe A

    更新日期:2020-01-01 00:00:00

  • Cocrystalline Solids of Telaprevir with Enhanced Oral Absorption.

    abstract::A combination of coformer screening and modeling, followed by characterization using calorimetry, structure elucidation, and solubility led to the identification of novel crystalline forms of the hepatitis C protease inhibitor, telaprevir. The lead crystalline form, a cocrystalline solid of telaprevir with 4-aminosaly...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.24534

    authors: Stavropoulos K,Johnston SC,Zhang Y,Rao BG,Hurrey M,Hurter P,Topp EM,Kadiyala I

    更新日期:2015-10-01 00:00:00

  • A physiologically relevant pharmacokinetic model of xenobiotic percutaneous absorption utilizing the isolated perfused porcine skin flap.

    abstract::A physiologic pharmacokinetic model describing percutaneous absorption of topically applied compounds in the isolated perfused porcine skin flap (IPPSF) is presented. As an extension of a previously reported hybrid physiologically relevant compartmental model of uptake of intra-arterially administered drug in the IPPS...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.2600790407

    authors: Williams PL,Carver MP,Riviere JE

    更新日期:1990-04-01 00:00:00

  • Onion phases of PEG-8 distearate.

    abstract::The aims of the present study were to formulate stable onion phases of the biodegradable surfactant PEG-8 Distearate (PEG8DS) and evaluate application of the onion phases in encapsulating sumatriptan succinate, a BCS class III potent antimigraine drug. Drug loaded and placebo onion phases were prepared by shearing lyo...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.20863

    authors: Redkar M,Hassan PA,Aswal V,Devarajan P

    更新日期:2007-09-01 00:00:00

  • Synthesis and characterization of surface-hydrophobic ion-exchange microspheres and the effect of coating on drug release rate.

    abstract::Biodegradable, dextran-based ion-exchange microspheres (IE-MS) have been used for localized delivery of anticancer drugs and chemosensitizers. Because of their hydrophilic nature, the IE-MS release their payload quickly. The purpose of this work was to develop an IE-MS system that could provide a broad range of releas...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/(SICI)1520-6017(200006)89:6<807::AID-JPS13

    authors: Liu Z,Wu XY,Ballinger JR,Bendayan R

    更新日期:2000-06-01 00:00:00

  • Understanding disintegrant action by visualization.

    abstract::The aim of this study was to utilize high-speed video imaging for understanding the disintegrability of compacts and disintegrant action upon wetting. High-speed video imaging was used to visualize the disintegration of compacts and effect of wetting on free disintegrant particles. Acquired images were processed using...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.23119

    authors: Desai PM,Liew CV,Heng PW

    更新日期:2012-06-01 00:00:00