Targeted delivery of complexes of biotin-PEG-polyethylenimine and NF-kappaB decoys to brain-derived endothelial cells in vitro.

Abstract:

PURPOSE:To evaluate the effect of re-directing the uptake mechanism of polyplexes containing oligodeoxynucleotide (ODN) decoys to nuclear factor kappa B (NF-kappaB) from absorptive-mediated to receptor-mediated endocytosis. MATERIALS AND METHODS:Complexes of ODNs and a co-polymer of biotin-polyethylenglycol and polyethylenimine (BPP) were targeted to brain-derived endothelial cells with a conjugate of antibody 8D3 and streptavidin (8D3SA). Size and stability of ODN/BPP complexes was measured by dynamic light scattering. Cellular uptake was studied by confocal microscopy. Cell viability and pharmacological effects were investigated on murine bEnd5 cells stimulated with tumor necrosis factor. RESULTS:ODN/BPP complexes showed sizes of 116+/-2.3 nm, which increased by 40 nm when coupled to 8D3SA, and were stable in physiological fluids. Targeted complexes were internalized intact into endosomal compartments. Treatment conditions, which yielded significant inhibitory effects on mRNA expression of VCAM-1, ICAM-1, IkappaBalpha and iNOS by bEnd5 cells, did not affect viability. At 0.5 microM, decoy ODN significantly inhibited monocyte adhesion to bEnd5 monolayers when delivered as 8D3SA-targeted complex, while higher concentrations of untargeted complex were ineffective. CONCLUSIONS:The complex of NF-kappaB decoys and BPP, which can be targeted to transferrin receptors, is a promising drug candidate for neuroinflammatory diseases affecting the blood-brain barrier.

journal_name

Pharm Res

journal_title

Pharmaceutical research

authors

Bhattacharya R,Osburg B,Fischer D,Bickel U

doi

10.1007/s11095-007-9389-y

subject

Has Abstract

pub_date

2008-03-01 00:00:00

pages

605-15

issue

3

eissn

0724-8741

issn

1573-904X

journal_volume

25

pub_type

杂志文章
  • In Silico Prediction of Diffusion Interaction Parameter (kD), a Key Indicator of Antibody Solution Behaviors.

    abstract:PURPOSE:To develop resource-sparing in silico approaches that aim to reduce experimental effort and material required by developability assessments (DA) of monoclonal antibody (mAb) drug candidates. METHODS:A battery of standardized biophysical experiments was performed on high concentration formulations of 16 drug pr...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1007/s11095-018-2466-6

    authors: Tomar DS,Singh SK,Li L,Broulidakis MP,Kumar S

    更新日期:2018-08-20 00:00:00

  • Functional identification of a novel transport system for endogenous and synthetic opioid peptides in the rabbit conjunctival epithelial cell line CJVE.

    abstract:PURPOSE:To investigate whether conjunctival epithelial cells express transport processes for opioid peptides. METHODS:We monitored the uptake of [(3)H]deltorphin II and [(3)H]DADLE, two hydrolysis-resistant synthetic opioid peptides, in the rabbit conjunctival epithelial cell line CJVE and elucidated the characteristi...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1007/s11095-008-9709-x

    authors: Ananth S,Karunakaran S,Martin PM,Nagineni CN,Hooks JJ,Smith SB,Prasad PD,Ganapathy V

    更新日期:2009-05-01 00:00:00

  • Probing the Distribution of Water in a Multi-Component System by Solid-State NMR Spectroscopy.

    abstract:PURPOSE:To characterize the distribution of water among various components in a powder blend using solid-state NMR spectroscopy. METHODS:Water sorption behavior of theophylline anhydrate and excipients was determined by dynamic vapor sorption (DVS) and Karl Fischer Titration (KFT) after storing them in humidity chambe...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1007/s11095-016-1972-7

    authors: Mistry P,Chakravarty P,Lubach JW

    更新日期:2016-10-01 00:00:00

  • Modification of the P-glycoprotein dependent pharmacokinetics of digoxin in rats by human recombinant interferon-alpha.

    abstract:PURPOSE:This study was conducted to investigate in vivo the impact of interferon-alpha (IFN)-alpha on P-glycoprotein (P-gp) activity in rats by studying how its administration modifies the bioavailability of digoxin, a fairly pure P-gp substrate. METHODS:Human recombinant IFN-alpha was given to rats (n = 5-7 per group...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1007/s11095-005-7415-5

    authors: Ben Reguiga M,Bonhomme-Faivre L,Orbach-Arbouys S,Farinotti R

    更新日期:2005-11-01 00:00:00

  • Controlled release of a contraceptive steroid from biodegradable and injectable gel formulations: in vitro evaluation.

    abstract:PURPOSE:The purpose of this study was to investigate the effects of formulation factors including varying wax concentration, drug loading and drug particle size, on drug release characteristics from both pure oil and gel formulations prepared with a combination of derivatized vegetable oil (Labrafil 1944 CS) and glycer...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1023/a:1016209020160

    authors: Gao ZH,Shukla AJ,Johnson JR,Crowley WR

    更新日期:1995-06-01 00:00:00

  • Intestinal absorption of miltefosine: contribution of passive paracellular transport.

    abstract:PURPOSE:This study aimed to characterize the transepithelial transport of miltefosine (HePC), the first orally effective drug against visceral leishmaniasis, across the intestinal barrier to further understand its oral absorption mechanism. MATERIALS AND METHODS:Caco-2 cell monolayers were used as an in vitro model of...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1007/s11095-006-9170-7

    authors: Ménez C,Buyse M,Dugave C,Farinotti R,Barratt G

    更新日期:2007-03-01 00:00:00

  • Bioavailability and pharmacokinetics of a new sustained-release potassium chloride tablet.

    abstract::The bioavailability of a new sustained-release potassium chloride (KCl) tablet, designed for once-a-day dosing, was compared to a KCl elixir using urinary excretion data. The study utilized 25 male volunteers dosed in a crossover design in a dietary/activity-controlled environment. The regimens consisted of a total of...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1023/a:1016438413297

    authors: Betlach CJ,Arnold JD,Frost RW,Leese PT,Gonzalez MA

    更新日期:1987-10-01 00:00:00

  • Grapefruit juice activates P-glycoprotein-mediated drug transport.

    abstract:PURPOSE:Grapefruit juice (GJ) is known to increase the oral bioavailability of many CYP3A-substrates by inhibiting intestinal phase-I metabolism. However, the magnitude of AUC increase is often insignificant and highly variable. Since we earlier suggested that CYP3A and P-glycoprotein (P-gp) form a concerted barrier to...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1023/a:1011902625609

    authors: Soldner A,Christians U,Susanto M,Wacher VJ,Silverman JA,Benet LZ

    更新日期:1999-04-01 00:00:00

  • Formulating paclitaxel in nanoparticles alters its disposition.

    abstract:PURPOSE:Paclitaxel is active and widely used to treat multiple types of solid tumors. The commercially available paclitaxel formulation uses Cremophor/ethanol (C/E) as the solubilizers. Other formulations including nanoparticles have been introduced. This study evaluated the effects of nanoparticle formulation of pacli...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1007/s11095-005-4581-4

    authors: Yeh TK,Lu Z,Wientjes MG,Au JL

    更新日期:2005-06-01 00:00:00

  • Structure-activity relationships for substrates and inhibitors of mammalian liver microsomal carboxylesterases.

    abstract:PURPOSE:Carboxylesterases are important in the detoxification of drugs, pesticides and other xenobiotics. This study was to evaluate a series of substrates and inhibitors for characterizing these enzymes. METHODS:A series of novel aliphatic esters and thioesters were used in spectral assays to monitor human, murine an...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1023/a:1016071311190

    authors: Huang TL,Shiotsuki T,Uematsu T,Borhan B,Li QX,Hammock BD

    更新日期:1996-10-01 00:00:00

  • Novel mucosal insulin delivery systems based on fusogenic liposomes.

    abstract:PURPOSE:Fusogenic liposomes (FLs) are unique delivery vehicles capable of introducing their contents directly into the cytoplasm with the aid of envelope glycoproteins of Sendai virus (SeV). The objective of this study was to evaluate the potential of FL to improve the mucosal absorption of insulin from rat intestinal ...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1007/s11095-005-9175-7

    authors: Goto T,Morishita M,Nishimura K,Nakanishi M,Kato A,Ehara J,Takayama K

    更新日期:2006-02-01 00:00:00

  • Effect of polymer blending on the release of ganciclovir from PLGA microspheres.

    abstract:PURPOSE:The aim of the study is to investigate the effect of polymer blending on entrapment and release of ganciclovir (GCV) from poly(D,L-lactide-co-glycolide) (PLGA) microspheres using a set of empirical equations. METHODS:Two grades of PLGA, PLGA 7525 [D,L-lactide:glycolide(75:25), MW 90,000-126,000 Da] and Resomer...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1007/s11095-005-9042-6

    authors: Duvvuri S,Gaurav Janoria K,Mitra AK

    更新日期:2006-01-01 00:00:00

  • Novel beads made of alpha-cyclodextrin and oil for topical delivery of a lipophilic drug.

    abstract:PURPOSE:To investigate the potential of a novel lipid carrier, comprising beads of alpha-cyclodextrin and soybean oil, for topical drug delivery. Adapalene was chosen as a model drug to explore the ability of the beads to encapsulate and release a highly lipophilic compound. MATERIALS AND METHODS:Adapalene-loaded bead...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1007/s11095-007-9395-0

    authors: Trichard L,Delgado-Charro MB,Guy RH,Fattal E,Bochot A

    更新日期:2008-02-01 00:00:00

  • Competitive inhibition of glycylsarcosine transport by enalapril in rabbit renal brush border membrane vesicles: interaction of ACE inhibitors with high-affinity H+/peptide symporter.

    abstract:PURPOSE:To examine the inhibitory potential of enalapril [and other angiotensin converting enzyme (ACE) inhibitors] on glycylsarcosine (GlySar) transport by the high-affinity renal peptide transporter. METHODS:Studies were performed in rabbit renal brush border membrane vesicles in which the uptake of radiolabeled Gly...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1023/a:1018847818766

    authors: Lin CJ,Akarawut W,Smith DE

    更新日期:1999-05-01 00:00:00

  • Aerosol dispersion of respirable particles in narrow size distributions produced by jet-milling and spray-drying techniques.

    abstract:PURPOSE:To examine the effect of particle size and morphology on aerosol dispersion using jet-milled and spray-dried mannitol particles in narrow size distributions within the respirable range. METHODS:Particle size and morphology were examined by laser diffraction and scanning electron microscopy, respectively. Aeros...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1023/b:pham.0000033007.27278.60

    authors: Louey MD,Van Oort M,Hickey AJ

    更新日期:2004-07-01 00:00:00

  • Mechanisms of tumor vascular priming by a nanoparticulate doxorubicin formulation.

    abstract:PURPOSE:Tumor vascular normalization by antiangiogenic agents may increase tumor perfusion but reestablish vascular barrier properties in CNS tumors. Vascular priming via nanoparticulate carriers represents a mechanistically distinct alternative. This study investigated mechanisms by which sterically-stabilized liposom...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1007/s11095-012-0823-4

    authors: Roy Chaudhuri T,Arnold RD,Yang J,Turowski SG,Qu Y,Spernyak JA,Mazurchuk R,Mager DE,Straubinger RM

    更新日期:2012-12-01 00:00:00

  • Selective contrast enhancement of individual Alzheimer's disease amyloid plaques using a polyamine and Gd-DOTA conjugated antibody fragment against fibrillar Abeta42 for magnetic resonance molecular imaging.

    abstract:PURPOSE:The lack of an in vivo diagnostic test for AD has prompted the targeting of amyloid plaques with diagnostic imaging probes. We describe the development of a contrast agent (CA) for magnetic resonance microimaging that utilizes the F(ab')2 fragment of a monoclonal antibody raised against fibrillar human Abeta42 ...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1007/s11095-008-9600-9

    authors: Ramakrishnan M,Wengenack TM,Kandimalla KK,Curran GL,Gilles EJ,Ramirez-Alvarado M,Lin J,Garwood M,Jack CR Jr,Poduslo JF

    更新日期:2008-08-01 00:00:00

  • A pharmacokinetic model of intravenously administered hyaluronan in sheep.

    abstract::Hyaluronan (HA: hyaluronic acid) is produced in the interstitium and reaches the blood circulation through the lymph. It is rapidly eliminated by means of specific receptors on liver endothelium. The elimination characteristics of intravenously administered HA were studied in 10 conscious sheep at the normal plasma HA...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1023/a:1015982204926

    authors: Lebel L,Fraser JR,Kimpton WS,Gabrielsson J,Gerdin B,Laurent TC

    更新日期:1989-08-01 00:00:00

  • Microdialysis sampling for determination of plasma protein binding of drugs.

    abstract::The use of microdialysis sampling to study the binding of drugs to plasma proteins was evaluated. Microdialysis sampling is accomplished by placing a short length of dialysis fiber in the sample and perfusing the fiber with a vehicle. Small molecules in the sample, such as drugs, diffuse into the fiber and are transpo...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1023/a:1015955503708

    authors: Herrera AM,Scott DO,Lunte CE

    更新日期:1990-10-01 00:00:00

  • An in vitro/in vivo correlation for the disintegration and onset of drug release from enteric-coated pellets.

    abstract::An empirical mass-transfer model for enteric-coating dissolution that uses in vivo dissolution data to characterize the pH-dependent solubility properties of the polymer film and a mass-transfer coefficient determined from in vivo dissolution or disintegration studies is developed. Once the in vivo mass-transfer coeff...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1023/a:1018986827350

    authors: Ebel JP,Jay M,Beihn RM

    更新日期:1993-02-01 00:00:00

  • Recrystallization and Water Absorption Properties of Vitrified Trehalose Near Room Temperature.

    abstract:PURPOSE:To provide the physicochemical properties of vitrified trehalose for predicting its recrystallization. METHODS:Thin films of vitrified trehalose solutions were prepared at room temperature and exposed to various humid and temperature atmospheres. The in-situ amount of retained water in the vacuum-dried trehalo...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1007/s11095-018-2420-7

    authors: Shirakashi R,Takano K

    更新日期:2018-05-10 00:00:00

  • Acylation of exenatide by glycolic acid and its anti-diabetic activities in db/db mice.

    abstract:PURPOSE:To prepare acylated exenatide analogues and investigate their biological properties for guiding the development of PLGA formulations of exenatide. METHODS:The acylated exenatide analogues were prepared by reaction with glycolic acid (GA), one constitutional unit of PLGA, and characterized by HPLC-MS/MS and Cir...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1007/s11095-014-1298-2

    authors: Liang R,Li X,Zhang R,Shi Y,Wang A,Chen D,Sun K,Liu W,Li Y

    更新日期:2014-08-01 00:00:00

  • Optical purity determination of threo-methylphenidate hydrochloride using a chiral europium nuclear magnetic resonance (NMR) shift reagent.

    abstract::A 1H-NMR spectroscopic method for the determination of the optical purity of threo-methylphenidate hydrochloride is presented. Complexation of the free-base form of the substrate with a chiral Eu(III) shift reagent resulted in two distinct enantiomeric ester methyl proton signals of utility for quantitative work. The ...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1023/a:1015815605583

    authors: Hanna GM,Lau-Cam CA

    更新日期:1990-07-01 00:00:00

  • Effects of variation in drug elimination on five methods for assessing zero-order drug absorption rates.

    abstract::The area function method for assessing zero-order (ko) drug absorption rates was compared to four other methods under conditions where variation occurs in the plasma concentration data and in the elimination rate constant (kel or k10) for one- or two-compartment models. For deviant kel values of a one-compartment mode...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1023/a:1015843811150

    authors: Cheng HY,Jusko WJ

    更新日期:1990-01-01 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

  • Microinfusion using hollow microneedles.

    abstract:PURPOSE:The aim of the study is to determine the effect of experimental parameters on microinfusion through hollow microneedles into skin to optimize drug delivery protocols and identify rate-limiting barriers to flow. METHODS:Glass microneedles were inserted to a depth of 720-1080 microm into human cadaver skin to mi...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1007/s11095-005-8498-8

    authors: Martanto W,Moore JS,Kashlan O,Kamath R,Wang PM,O'Neal JM,Prausnitz MR

    更新日期:2006-01-01 00:00:00

  • Anti-melanoma effects of vorinostat in combination with polyphenolic antioxidant (-)-epigallocatechin-3-gallate (EGCG).

    abstract:PURPOSE:Melanoma is an aggressive neoplasm with a propensity for metastases and resistance to therapy. Previously, we showed that (-)-epigallocatechin-3-gallate (EGCG), the major polyphenolic antioxidant present in green tea, resulted in a significant decrease in the viability and growth of melanoma and induction of ap...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1007/s11095-010-0054-5

    authors: Nihal M,Roelke CT,Wood GS

    更新日期:2010-06-01 00:00:00

  • Body distribution of camptothecin solid lipid nanoparticles after oral administration.

    abstract:PURPOSE:The aim of this study was to investigate the specific changes in body distribution of camptothecin (CA) through incorporation into solid lipid nanoparticles (SLN) by peroral route. METHODS:Camptothecin loaded solid lipid nanoparticles (CA-SLN) coated with poloxamer 188 were produced by high pressure homogeniza...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1023/a:1018888927852

    authors: Yang S,Zhu J,Lu Y,Liang B,Yang C

    更新日期:1999-05-01 00:00:00

  • The use of disaccharides in inhibiting enzymatic activity loss and secondary structure changes in freeze-dried β-galactosidase during storage.

    abstract:PURPOSE:The purpose of this study is to show how disaccharides differ in their ability to protect lyophilized β-galactosidase from enzymatic activity loss and secondary structure changes during storage. METHODS:β-galactosidase was lyophilized with trehalose, sucrose, cellobiose or melibiose at 2:1, 20:1 and 40:1 excip...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1007/s11095-010-0300-x

    authors: Heljo VP,Jouppila K,Hatanpää T,Juppo AM

    更新日期:2011-03-01 00:00:00

  • Long-Acting Phospholipid Gel of Exenatide for Long-Term Therapy of Type II Diabetes.

    abstract:PURPOSE:This study aimed to develop a sustained-release formulation of exenatide (EXT) for the long-term therapeutic efficacy in the treatment of type II diabetes. METHODS:In this study, we present an injectable phospholipid gel by mixing biocompatible phospholipid S100, medium chain triglyceride (MCT) with 85% (w/w) ...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1007/s11095-016-1873-9

    authors: Hu M,Zhang Y,Xiang N,Zhong Y,Gong T,Zhang ZR,Fu Y

    更新日期:2016-06-01 00:00:00