Enhanced doxorubicin delivery to the brain administered through glutathione PEGylated liposomal doxorubicin (2B3-101) as compared with generic Caelyx,(®)/Doxil(®)--a cerebral open flow microperfusion pilot study.

Abstract:

:The neuroprotective blood-brain barrier (BBB) keeps many drug candidates below therapeutic levels in the central nervous system. Glutathione PEGylated liposomal doxorubicin (2B3-101) has been developed to safely enhance the delivery of doxorubicin to brain tumors. However, doxorubicin concentration in extracellular brain fluid cannot yet be reliably measured using conventional techniques. Cerebral open flow microperfusion (cOFM), a recently developed sampling technique, allows monitoring of drug concentrations in the brain independent of molecular weight and lipophilicity. In combination with cOFM sampling, sodium fluorescein (NaF) is used as a marker for BBB integrity. Rats received one intravenous dose of 7 mg/kg of either 2B3-101 or PEGylated liposomal doxorubicin (generic Caelyx(®)). Blood and cOFM sampling was performed for 5 h after dose injection. NaF concentration in the brain was monitored and remained low indicating an intact BBB. The brain-to-blood ratio of doxorubicin was 4.8-fold higher after administration of 2B3-101 as compared with generic Caelyx(®) (p = 0.0016). In conclusion, by using cOFM it was possible to show that 2B3-101 leads to enhanced doxorubicin concentration in the brain without affecting the BBB integrity.

journal_name

J Pharm Sci

authors

Birngruber T,Raml R,Gladdines W,Gatschelhofer C,Gander E,Ghosh A,Kroath T,Gaillard PJ,Pieber TR,Sinner F

doi

10.1002/jps.23994

subject

Has Abstract

pub_date

2014-07-01 00:00:00

pages

1945-1948

issue

7

eissn

0022-3549

issn

1520-6017

pii

S0022-3549(15)30507-4

journal_volume

103

pub_type

杂志文章
  • Developability index: a rapid in silico tool for the screening of antibody aggregation propensity.

    abstract::Determining the aggregation propensity of protein-based biotherapeutics is an important step in the drug development process. Typically, a great deal of data collected over a large period of time is needed to estimate the aggregation propensity of biotherapeutics. Thus, candidates cannot be screened early on for aggre...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.22758

    authors: Lauer TM,Agrawal NJ,Chennamsetty N,Egodage K,Helk B,Trout BL

    更新日期:2012-01-01 00:00:00

  • Cerebral kinetics of oxycodone in conscious sheep.

    abstract::Oxycodone is an opioid analgesic that is administered orally or parenterally. The time-course of opioid action is a function of the systemic kinetics of the opioid, and the rate and extent of its entry into the brain and central nervous system. The latter is incompletely understood for oxycodone. Therefore, the cerebr...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.20632

    authors: Villesen HH,Foster DJ,Upton RN,Somogyi AA,Martinez A,Grant C

    更新日期:2006-08-01 00:00:00

  • Slow-release characteristics of diltiazem from ethylated beta-cyclodextrin complexes.

    abstract::Release characteristics of two ethylated beta-cyclodextrins [heptakis(2,6-di-O-ethyl)-beta-cyclodextrin (diethyl-beta-cyclodextrin) and heptakis(2,3,6-tri-O-ethyl)-beta-cyclodextrin (triethyl-beta-cyclodextrin)] as sustained-release drug carriers were evaluated using diltiazem hydrochloride, a water-soluble calcium an...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.2600790211

    authors: Horiuchi Y,Hirayama F,Uekama K

    更新日期:1990-02-01 00:00:00

  • An Assessment of the Ability of Submicron- and Micron-Size Silicone Oil Droplets in Dropped Prefillable Syringes to Invoke Early- and Late-Stage Immune Responses.

    abstract::A number of biopharmaceuticals are available as lyophilized formulations along with a prefilled syringe (PFS) containing water for injection (WFI). Submicron- and micron-size droplets of lubricating silicone oil (SO) applied to the inner surface of the PFS barrel might migrate into the WFI, to which protein pharmaceut...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1016/j.xphs.2019.02.002

    authors: Krayukhina E,Yokoyama M,Hayashihara KK,Maruno T,Noda M,Watanabe H,Uchihashi T,Uchiyama S

    更新日期:2019-07-01 00:00:00

  • Evaluation of "external" predictability of an in vitro-in vivo correlation for an extended-release formulation containing metoprolol tartrate.

    abstract::The purpose of this study was to examine the external predictability of an in vitro-in vivo correlation (IVIVC) for a metoprolol hydrophilic matrix extended-release formulation, with an acceptable internal predictability, in the presence of a range of formulation/manufacturing changes. In addition, this report evaluat...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1002/1520-6017(200010)89:10<1354::aid-jps13>3.0

    authors: Mahayni H,Rekhi GS,Uppoor RS,Marroum P,Hussain AS,Augsburger LL,Eddington ND

    更新日期:2000-10-01 00:00:00

  • Determination of benzalkonium chloride by reversed-phase high-pressure liquid chromatography.

    abstract::A new, specific, and useful approach for the analysis of benzalkonium chloride is presented. Reversed-phase high-pressure liquid chromatography is used to determine benzalkonium chloride in an ophthalmic system at the presevative level of 0.004%. Since the method separates each homolog, it can be extended to determine...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.2600691006

    authors: Meyer RC

    更新日期:1980-10-01 00:00:00

  • In Vitro Evaluation of Novel Phenytoin-Loaded Alkyd Nanoemulsions Designed for Application in Topical Wound Healing.

    abstract::Phenytoin-loaded alkyd nanoemulsions were prepared spontaneously using the phase inversion method from a mixture of novel biosourced alkyds and Tween 80 surfactant. Exposure of human adult keratinocytes (HaCaT cells) for 48 h to alkyd nanoemulsions producing phenytoin concentrations of 3.125-200 μg/mL resulted in rela...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1016/j.xphs.2016.06.028

    authors: Teo SY,Yew MY,Lee SY,Rathbone MJ,Gan SN,Coombes AGA

    更新日期:2017-01-01 00:00:00

  • A high-throughput UPLC method for the characterization of chemical modifications in monoclonal antibody molecules.

    abstract::Development of high-throughput release and characterization assays is critical for the effective support of the rapidly growing biologics pipeline for biotherapeutics. Clipping of polypeptide chains is commonly monitored during process optimization, formulation development, and stability studies. A reduced capillary e...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.22710

    authors: Stackhouse N,Miller AK,Gadgil HS

    更新日期:2011-12-01 00:00:00

  • Toward Understanding Drug Release From Biodegradable Polymer Microspheres of Different Erosion Kinetics Modes.

    abstract::Two generalized modes of erosion kinetics, that is, the power law mode and root type mode, respectively, were found to be able to better describe the reported weight loss data compared to the existing linear mode, for commonly used surface-eroding polymer microspheres. Based on the newly identified modes, a set of dru...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1016/j.xphs.2016.04.002

    authors: You S,Yang Z,Wang CH

    更新日期:2016-06-01 00:00:00

  • Progestin permeation through polymer membrane V: Progesterone release from monolithic hydrogel devices.

    abstract::Progesterone release from monolithic devices prepared from various copolymers of poly(hydroxyethyl methacrylate) and poly(methoxyethoxyethyl methacrylate) or poly(methoxyethyl methacrylate) was examined. In general, plots of the fraction of drug released versus (time)1/2 were linear during the early stages of drug rel...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.2600700226

    authors: Song SZ,Cardinal JR,Kim SH,Kim SW

    更新日期:1981-02-01 00:00:00

  • Hydrogen-bonded complexes between chloral hydrate and halide ions in aqueous solution.

    abstract::The hydrogen-bonded interactions of chloral hydrate and halide ions have been investigated conductometrically at 25.00 degrees C in aqueous solutions. In spite of the strong competing effect of water, the 1:1 associates have relatively high stability constants, in the order of chloride greater than bromide greater tha...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.2600770714

    authors: Barcza L,Lenner L

    更新日期:1988-07-01 00:00:00

  • pH indicator titration: a novel fast pKa determination method.

    abstract::This study describes a fast spectrophotometic titration method for apparent ionization constant (pKa) determination. In this method, a Universal pH indicator is utilized instead of the conventional pH electrode. An autoburette is set to add HCl at a constant rate to a vigorously stirred 1 cm UV cuvette which contains ...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.20959

    authors: Kong X,Zhou T,Liu Z,Hider RC

    更新日期:2007-10-01 00:00:00

  • Determination of polymorph conversion of an active pharmaceutical ingredient in wet granulation using NIR calibration models generated from the premix blends.

    abstract::Near infrared (NIR) spectroscopy was used for quantitatively monitoring polymorph conversion of an active pharmaceutical ingredient (API) in wet granulation. The API under pharmaceutical development has two different polymorphs. Polymorph A is the stable form for drug development and polymorph B is the undesired form ...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.20501

    authors: Li W,Worosila GD,Wang W,Mascaro T

    更新日期:2005-12-01 00:00:00

  • Formation of a cyclic derivative of ethacrynic acid with diazomethane.

    abstract::Samples of ethacrynic acid were treated with methanol-hydrochloric acid or with diazomethane. GLC and mass spectrometric analysis indicated that the methanol-hydrochloric acid reaction gave the expected methyl ester, whereas diazomethane treatment gave a compound containing an additional 14 mass units. Accurate mass m...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.2600670728

    authors: Midha KK,Hubbard JW,Charette C,Jun HW

    更新日期:1978-07-01 00:00:00

  • Differences in Food Effects for 2 Weak Bases With Similar BCS Drug-Related Properties: What Is Happening in the Intestinal Lumen?

    abstract::Ketoconazole and posaconazole are both Biopharmaceutics Classification System class 2 drugs (highly permeable, poorly soluble), are structurally similar, and are administered at the same doses. Nevertheless, the duodenal concentration profile and the magnitude of the positive food effect observed for these 2 drugs are...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1016/j.xphs.2015.11.033

    authors: Cristofoletti R,Patel N,Dressman JB

    更新日期:2016-09-01 00:00:00

  • Synthesis and anti-inflammatory activity of 3-(benzylideneamino)coumarins in rodents.

    abstract::A series of substituted 3-(benzylideneamino) coumarins was synthesized and evaluated for anti-inflammatory activity against carrageenan-induced edema in rats. Halogenated derivatives 4g and 4c, at oral doses of 100 mg/kg, showed 75 and 60% antiedmatous activity, respectively (phenylbutazone antiedematous activity, 58%...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.2600810926

    authors: Maddi V,Raghu KS,Rao MN

    更新日期:1992-09-01 00:00:00

  • Development of respirable nanomicelle carriers for delivery of amphotericin B by jet nebulization.

    abstract::The aim of the present work was to prepare and characterize chitosan-stearic acid conjugate nanomicelles for encapsulation of amphotericin B (AmB) and to evaluate the in vitro nebulization of the formulations. Water soluble chitosan was grafted to stearic acid (SA) chains via 1-ethyl-3-(3-dimethylaminopropyl)carbodiim...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.22274

    authors: Gilani K,Moazeni E,Ramezanli T,Amini M,Fazeli MR,Jamalifar H

    更新日期:2011-01-01 00:00:00

  • High-Throughput Melanin-Binding Affinity and In Silico Methods to Aid in the Prediction of Drug Exposure in Ocular Tissue.

    abstract::Drugs possessing the ability to bind to melanin-rich tissue, such as the eye, are linked with higher ocular exposure, and therefore have the potential to affect the efficacy and safety profiles of therapeutics. A high-throughput melanin chromatographic affinity assay has been developed and validated, which has allowed...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.24680

    authors: Reilly J,Williams SL,Forster CJ,Kansara V,End P,Serrano-Wu MH

    更新日期:2015-12-01 00:00:00

  • Membrane transport of drugs in different regions of the intestinal tract of the rat.

    abstract::Regional permeability coefficients of 19 drugs with different physicochemical properties were determined using excised segments from three regions of rat intestine: jejunum, ileum, and colon. The results are discussed in relation to the characteristics of the drug, i.e., MW (range 113-1071 Da), pKa, log D (octanol/wat...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1021/js970218s

    authors: Ungell AL,Nylander S,Bergstrand S,Sjöberg A,Lennernäs H

    更新日期:1998-03-01 00:00:00

  • Moisture sorption kinetics for water-soluble substances. I: Theoretical considerations of heat transport control.

    abstract::A model based on heat transport control was developed to describe the uptake of water on a deliquescent solid in an atmosphere of pure water vapor. The model assumes the presence of a saturated liquid film on the surface of the solid. The decrease in the vapor pressure of water over the surface, brought about by the c...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.2600721204

    authors: Van Campen L,Amidon GL,Zografi G

    更新日期:1983-12-01 00:00:00

  • Limits on optimizing ocular drug delivery.

    abstract::The problem of optimizing ocular bioavailability of topically applied ophthalmic drugs is discussed. A formula for drug concentration in the tear film is derived using well-known pharmacokinetic relationships and a first-order drug decay model for the tear film. The time integral of the tear film concentration is then...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.2600800113

    authors: Keister JC,Cooper ER,Missel PJ,Lang JC,Hager DF

    更新日期:1991-01-01 00:00:00

  • Do multidrug resistance-associated protein-1 and -2 play any role in the elimination of estradiol-17 beta-glucuronide and 2,4-dinitrophenyl-S-glutathione across the blood-cerebrospinal fluid barrier?

    abstract::The purpose of this study was to examine the role of multidrug resistance-associated protein-1 and -2 (Mrp1 and Mrp2) in the efflux transport of organic anions across the blood-cerebrospinal fluid (CSF) barrier. The CSF concentration of estradiol-17beta-glucuronide (E(2)17betaG) and 2,4-dinitrophenyl-S-glutathione (DN...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.10521

    authors: Lee YJ,Kusuhara H,Sugiyama Y

    更新日期:2004-01-01 00:00:00

  • No clinically relevant pharmacokinetic and safety interactions of ambrisentan in combination with tadalafil in healthy volunteers.

    abstract::Ambrisentan is a nonsulfonamide, ET(A)-selective endothelin receptor antagonist (ERA) approved for the treatment of pulmonary arterial hypertension (PAH), and tadalafil is a phosphodiesterase type 5 (PDE-5) inhibitor under investigation for treatment of PAH. Due to the potential combination use, the pharmacokinetic (P...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章,随机对照试验

    doi:10.1002/jps.21789

    authors: Spence R,Mandagere A,Harrison B,Dufton C,Boinpally R

    更新日期:2009-12-01 00:00:00

  • Evaluation of 6β-Hydroxycortisol and 6β-Hydroxycortisone as Biomarkers for Cytochrome P450 3A Activity: Insight into Their Predictive Value for Estimating Oral Immunosuppressant Metabolism.

    abstract::The combined clearance of endogenous 6β-hydroxycortisol and 6β-hydroxycortisone is suggested biomarker for in vivo cytochrome P450 3A (CYP3A) activity. We aimed to determine whether the combined clearance of these two markers together with information of biopharmaceutics classification system (BCS) of drugs could be u...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.24566

    authors: Luo X,Zheng L,Cai N,Liu Q,Yang S,He X,Cheng Z

    更新日期:2015-10-01 00:00:00

  • Derivative and graphical procedures for correction of irrelevant UV spectrophotometric absorption in changeable matrixes.

    abstract::The application of direct zero-order UV spectrophotometric and graphical or derivative background correction methods to selected pharmaceutical preparations shows their relative advantages in different situations. The assay of the active components in a changeable matrix is a problem with formulations having a limited...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.2600690605

    authors: Traveset J,Such V,Gonzalo R,Gelpi E

    更新日期:1980-06-01 00:00:00

  • Another model for giving.

    abstract::Most of the global healthcare issues facing us--from expanding access to care, to providing medical and dental care in the aftermath of disasters--are far too complex for any single sector to successfully solve. Industry, the healthcare profession, government, academia and non-governmental organizations (NGOs) are all...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.21557

    authors: Bergman SM

    更新日期:2008-12-01 00:00:00

  • Determination of time course of tablet disintegration II: Method using continuous functions.

    abstract::An analysis of the disintegration-dissolution sequence of drug release from a tablet leads to a mathematical expression relating disintegration to the dissolution profile of the tablet and the dissolution rate of the primary drug particles in the tablet. The equation describing the disintegration of an acetaminophen t...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.2600670122

    authors: Nelson KG,Wang LY

    更新日期:1978-01-01 00:00:00

  • Analysis of coating structures and interfaces in solid oral dosage forms by three dimensional terahertz pulsed imaging.

    abstract::Three dimensional terahertz pulsed imaging (TPI) was evaluated as a novel tool for the nondestructive characterization of different solid oral dosage forms. The time-domain reflection signal of coherent pulsed light in the far infrared was used to investigate film-coated tablets, sugar-coated tablets, multilayered con...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.20789

    authors: Zeitler JA,Shen Y,Baker C,Taday PF,Pepper M,Rades T

    更新日期:2007-02-01 00:00:00

  • ¹⁴N nuclear quadrupole resonance study of polymorphism in famotidine.

    abstract::(14)N nuclear quadrupole resonance (NQR) in two known polymorphs of famotidine was measured. At room temperature, seven quadrupolar sets of transition frequencies (ν(+), ν(-), and ν(0)) corresponding to seven different nitrogen sites in the crystal structure of each of the two polymorphs were found. This confirms the ...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.23956

    authors: Luźnik J,Pirnat J,Jazbinšek V,Lavrič Z,Žagar V,Srčič S,Seliger J,Trontelj Z

    更新日期:2014-09-01 00:00:00

  • Molecular complexes of alprazolam with carboxylic acids, boric acid, boronic acids, and phenols. Evaluation of supramolecular heterosynthons mediated by a triazole ring.

    abstract::A series of molecular complexes, both co-crystals and salts, of a triazole drug-alprazolam-with carboxylic acids, boric acid, boronic acids, and phenols have been analyzed with respect to heterosynthons present in the crystal structures. In all cases, the triazole ring behaves as an efficient hydrogen bond acceptor wi...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章

    doi:10.1002/jps.22117

    authors: Varughese S,Azim Y,Desiraju GR

    更新日期:2010-09-01 00:00:00