当前位置： SCI文献检索 > MOLECULAR PHARMACEUTICS期刊下所有文献 > The brain entry of HIV-1 protease inhibitors is facilitated when used in combination.

The brain entry of HIV-1 protease inhibitors is facilitated when used in combination.

Abstract：

:One hypothesis for persisting HIV-associated neurocognitive disorders (HAND) in effectively treated individuals is the limited permeation of antiretroviral agents (ARV) across the blood-brain barrier (BBB). However, the physicochemical factors limiting the brain entry of a given ARV and the mutual interactions of combined drugs on their brain entry have not been properly characterized. Using transporter kinetic measurements, we show that large lipophilic drugs such as protease inhibitors (PI) have strong binding affinities to drug efflux transporters expressed at the BBB and thus are prevented from entering the brain. However, when combined, the PI with the highest binding affinity (i.e., boosting ritonavir) will occupy a large proportion of the transporter binding sites and thus slow down the efflux rate of the coadministered PI thereby facilitating its brain entry. Furthermore, using thermodynamic measurements and computational modeling, we show that ARV with small cross-sectional areas (AD < 70 Å(2)) and octanol-water distribution coefficients (-1 < log D <5) such as most nucleoside analogues have a high passive influx and cross the BBB despite interactions with drug transporters. These data indicate that HIV therapies combining small diffusing molecules with large lipophilic molecules are better suited for brain entry and should be preferred for HAND. This work highlights the role of PI as modulators of drugs' brain entry.

journal_name

Mol Pharm

journal_title

Molecular pharmaceutics

authors

Marzolini C,Mueller R,Li-Blatter X,Battegay M,Seelig A

doi

10.1021/mp300712a

subject

Has Abstract

pub_date

2013-06-03 00:00:00

pages

2340-9

issue

6

eissn

1543-8384

issn

1543-8392

journal_volume

10

pub_type

杂志文章

相关文献

MOLECULAR PHARMACEUTICS文献大全
  • druGAN: An Advanced Generative Adversarial Autoencoder Model for de Novo Generation of New Molecules with Desired Molecular Properties in Silico.

    abstract：:Deep generative adversarial networks (GANs) are the emerging technology in drug discovery and biomarker development. In our recent work, we demonstrated a proof-of-concept of implementing deep generative adversarial autoencoder (AAE) to identify new molecular fingerprints with predefined anticancer properties. Another...

    journal_title：Molecular pharmaceutics

    pub_type： 杂志文章

    doi：10.1021/acs.molpharmaceut.7b00346

    authors： Kadurin A,Nikolenko S,Khrabrov K,Aliper A,Zhavoronkov A

    更新日期：2017-09-05 00:00:00

  • Click Biotinylation of PLGA Template for Biotin Receptor Oriented Delivery of Doxorubicin Hydrochloride in 4T1 Cell-Induced Breast Cancer.

    abstract：:PLGA was functionalized with PEG and biotin using click chemistry to generate a biotin receptor targeted copolymer (biotinylated-PEG-PLGA) which in turn was used to fabricate ultrafine nanoparticles (BPNP) of doxorubicin hydrochloride (DOX) for effective delivery in 4T1 cell induced breast cancer. However, adequate en...

    journal_title：Molecular pharmaceutics

    pub_type： 杂志文章

    doi：10.1021/acs.molpharmaceut.7b00310

    authors： Singh Y,Durga Rao Viswanadham KK,Kumar Jajoriya A,Meher JG,Raval K,Jaiswal S,Dewangan J,Bora HK,Rath SK,Lal J,Mishra DP,Chourasia MK

    更新日期：2017-08-07 00:00:00

  • Nanostructured Drugs Embedded into a Polymeric Matrix: Vinpocetine/PVP Hybrids Investigated by Debye Function Analysis.

    abstract：:Microcrystalline vinpocetine, coground with cross-linked polyvinylpyrrolidone, affords hybrids containing nanosized drug nanocrystals, the size and size distributions of which depend on milling times and drug-to-polymer weight ratios. Using an innovative approach to microstructural characterization, we analyzed wide-a...

    journal_title：Molecular pharmaceutics

    pub_type： 杂志文章

    doi：10.1021/acs.molpharmaceut.6b00124

    authors： Hasa D,Giacobbe C,Perissutti B,Voinovich D,Grassi M,Cervellino A,Masciocchi N,Guagliardi A

    更新日期：2016-09-06 00:00:00

  • FRET imaging approaches for in vitro and in vivo characterization of synthetic lipid nanoparticles.

    abstract：:DiI and DiD, two fluorophores able to interact by FRET (Förster resonance energy transfer), were coencapsulated in the core of lipid nanocapsules (LNCs) and nanoemulsions (LNEs), lipophilic reservoirs for the delivery of drugs. The ability of FRET imaging to provide information on the kinetics of dissociation of the n...

    journal_title：Molecular pharmaceutics

    pub_type： 杂志文章

    doi：10.1021/mp500329z

    authors： Gravier J,Sancey L,Hirsjärvi S,Rustique E,Passirani C,Benoît JP,Coll JL,Texier I

    更新日期：2014-09-02 00:00:00

  • Mechanism of Supersaturation Suppression in Dissolution Process of Acidic Drug Salt.

    abstract：:Supersaturable active pharmaceutical ingredients (sAPI), such as salts, cocrystals, and amorphous solids, can form supersaturated solutions after dissolving in the gastrointestinal fluids. However, there are cases in which supersaturation is not observed in an in vitro nonsink dissolution test. The purpose of the pres...

    journal_title：Molecular pharmaceutics

    pub_type： 杂志文章

    doi：10.1021/acs.molpharmaceut.9b00006

    authors： Oki J,Watanabe D,Uekusa T,Sugano K

    更新日期：2019-04-01 00:00:00

  • Alginate/CaCO3 hybrid nanoparticles for efficient codelivery of antitumor gene and drug.

    abstract：:In this study, a facile strategy for efficient codelivery of gene and drug was developed. Using a coprecipitation method, doxorubicin hydrochloride (DOX), an antitumor drug, and p53 expression plasmid were encapsulated in alginate/CaCO(3)/DNA/DOX nanoparticles with high encapsulation efficiency. The in vitro cell inhi...

    journal_title：Molecular pharmaceutics

    pub_type： 杂志文章

    doi：10.1021/mp3002123

    authors： Zhao D,Liu CJ,Zhuo RX,Cheng SX

    更新日期：2012-10-01 00:00:00

  • Effect of Seed Particles on Precipitation of Weak Base Drugs in Physiological Intestinal Conditions.

    abstract：:The purpose of the present study was to investigate the effect of seed particles on the precipitation behavior of weak base drugs in the small intestine. A simple in vitro infusion method was used to mimic in vivo processes. Dipyridamole, pioglitazone, topiroxostat, chlorpromazine, cinnarizine, and ketoconazole were u...

    journal_title：Molecular pharmaceutics

    pub_type： 杂志文章

    doi：10.1021/acs.molpharmaceut.6b00297

    authors： Koyama H,Ito M,Terada K,Sugano K

    更新日期：2016-08-01 00:00:00

  • Bacillus-shape design of polymer based drug delivery systems with janus-faced function for synergistic targeted drug delivery and more effective cancer therapy.

    abstract：:The particle shape of the drug delivery systems had a strong impact on their in vitro and in vivo performance, but there was limited availability of techniques to produce the specific shaped drug carriers. In this article, the novel methotrexate (MTX) decorated MPEG-PLA nanobacillus (MPEG-PLA-MTX NB) was prepared by t...

    journal_title：Molecular pharmaceutics

    pub_type： 杂志文章

    doi：10.1021/mp500464b

    authors： Cui F,Lin J,Li Y,Li Y,Wu H,Yu F,Jia M,Yang X,Wu S,Xie L,Ye S,Luo F,Hou Z

    更新日期：2015-04-06 00:00:00

  • Acetal derivatives as prodrugs of resveratrol.

    abstract：:The pharmacological exploitation of resveratrol is hindered by rapid phase-II conjugative metabolism in enterocytes and hepatocytes. One approach to the solution of this problem relies on prodrugs. We report the synthesis and characterization as well as the assessment of in vivo absorption and metabolism of a set of p...

    journal_title：Molecular pharmaceutics

    pub_type： 杂志文章

    doi：10.1021/mp400226p

    authors： Mattarei A,Azzolini M,Carraro M,Sassi N,Zoratti M,Paradisi C,Biasutto L

    更新日期：2013-07-01 00:00:00

  • Recent advances in intravesical drug/gene delivery.

    abstract：:Targeting of drugs administered systemically relies on the higher affinity of ligands for specific receptors to obtain selectivity in drug response. However, achieving the same goal inside the bladder is much easier with an intelligent pharmaceutical approach that restricts drug effects by exploiting the pelvic anatom...

    journal_title：Molecular pharmaceutics

    pub_type： 杂志文章,评审

    doi：10.1021/mp060001j

    authors： Tyagi P,Wu PC,Chancellor M,Yoshimura N,Huang L

    更新日期：2006-07-01 00:00:00

  • Design, synthesis, and characterization of new 5-fluorocytosine salts.

    abstract：:5-Fluorocytosine (FC), an antifungal drug and a cytosine derivative, has a complex solid-state landscape that challenges its development into a drug product. A total of eight new FC salts, both cytosinium and hemicytosinium, with four strong acids were prepared by controlling acid concentration in the crystallization ...

    journal_title：Molecular pharmaceutics

    pub_type： 杂志文章

    doi：10.1021/mp400070a

    authors： Perumalla SR,Pedireddi VR,Sun CC

    更新日期：2013-06-03 00:00:00

  • Cationic phospholipids forming cubic phases: lipoplex structure and transfection efficiency.

    abstract：:The transfection activity and the phase behavior of two novel cationic O-alkyl-phosphatidylcholines, 1,2-dioleoyl- sn-glycero-3-hexylphosphocholine (C6-DOPC) and 1,2-dierucoyl- sn-glycero-3-ethylphosphocholine (di22:1-EPC), have been examined with the aim of more completely understanding the mechanism of lipid-mediate...

    journal_title：Molecular pharmaceutics

    pub_type： 杂志文章

    doi：10.1021/mp800011e

    authors： Koynova R,Wang L,Macdonald RC

    更新日期：2008-09-01 00:00:00

  • Polyarginine molecular weight determines transfection efficiency of calcium condensed complexes.

    abstract：:Cell penetrating peptides (CPPs) have been extensively studied in polyelectrolyte complexes as a means to enhance the transfection efficiency of plasmid DNA (pDNA). Increasing the molecular weight of CPPs often enhances gene expression but poses a risk of increased cytotoxicity and immunogenicity compared to low molec...

    journal_title：Molecular pharmaceutics

    pub_type： 杂志文章

    doi：10.1021/mp3007117

    authors： Alhakamy NA,Berkland CJ

    更新日期：2013-05-06 00:00:00

  • Optimization of the Conditions for Plasmid DNA Delivery and Transfection with Self-Assembled Hyaluronic Acid-Based Nanoparticles.

    abstract：:Polymeric systems have been extensively studied as polyelectrolyte complexes to enhance the cellular delivery and transfection efficiency of genetic materials, such as plasmid DNA (pDNA). Here, self-assembled nanoparticles were formulated by complexation of hyaluronic acid (HA)-conjugated poly(ethylene glycol) (HA-PEG...

    journal_title：Molecular pharmaceutics

    pub_type： 杂志文章

    doi：10.1021/acs.molpharmaceut.8b00904

    authors： Aldawsari HM,Dhaliwal HK,Aljaeid BM,Alhakamy NA,Banjar ZM,Amiji MM

    更新日期：2019-01-07 00:00:00

  • ImmunoPET and Near-Infrared Fluorescence Imaging of Pancreatic Cancer with a Dual-Labeled Bispecific Antibody Fragment.

    abstract：:Dual-targeted imaging agents have shown improved targeting efficiencies in comparison to single-targeted entities. The purpose of this study was to quantitatively assess the tumor accumulation of a dual-labeled heterobifunctional imaging agent, targeting two overexpressed biomarkers in pancreatic cancer, using positro...

    journal_title：Molecular pharmaceutics

    pub_type： 杂志文章

    doi：10.1021/acs.molpharmaceut.6b01123

    authors： Luo H,England CG,Goel S,Graves SA,Ai F,Liu B,Theuer CP,Wong HC,Nickles RJ,Cai W

    更新日期：2017-05-01 00:00:00

  • Predicting the formation and stability of amorphous small molecule binary mixtures from computationally determined Flory-Huggins interaction parameter and phase diagram.

    abstract：:The Flory-Huggins interaction parameter has been shown to be useful in predicting the thermodynamic miscibility of a polymer and a small molecule in a binary mixture. In the present paper, this concept was extended and evaluated to determine whether or not the Flory-Huggins interaction parameter can be applied to smal...

    journal_title：Molecular pharmaceutics

    pub_type： 杂志文章

    doi：10.1021/mp900304p

    authors： Pajula K,Taskinen M,Lehto VP,Ketolainen J,Korhonen O

    更新日期：2010-06-07 00:00:00

  • Conjugates of superoxide dismutase 1 with amphiphilic poly(2-oxazoline) block copolymers for enhanced brain delivery: synthesis, characterization and evaluation in vitro and in vivo.

    abstract：:Superoxide dismutase 1 (SOD1) efficiently catalyzes dismutation of superoxide, but its poor delivery to the target sites in the body, such as brain, hinders its use as a therapeutic agent for superoxide-associated disorders. Here to enhance the delivery of SOD1 across the blood-brain barrier (BBB) and in neurons the e...

    journal_title：Molecular pharmaceutics

    pub_type： 杂志文章

    doi：10.1021/mp300496x

    authors： Tong J,Yi X,Luxenhofer R,Banks WA,Jordan R,Zimmerman MC,Kabanov AV

    更新日期：2013-01-07 00:00:00

  • Investigation of Spatial Heterogeneity of Salt Disproportionation in Tablets by Synchrotron X-ray Diffractometry.

    abstract：:Tablets which were binary mixtures of pioglitazone hydrochloride (PioHCl) with magnesium stearate (MgSt), croscarmellose sodium (CCS), microcrystalline cellulose, or lactose monohydrate were prepared. Two sets of experiments, using intact tablets, were performed. (i) Tablets containing PioHCl (90% w/w) and MgSt were e...

    journal_title：Molecular pharmaceutics

    pub_type： 杂志文章

    doi：10.1021/acs.molpharmaceut.6b01052

    authors： Koranne S,Govindarajan R,Suryanarayanan R

    更新日期：2017-04-03 00:00:00

  • Sustained release of transgenic human factor IX: preparation, characterization, and in vivo efficacy.

    abstract：:The current regimen of factor IX (FIX) injection is of an episodic format, which leads to limited efficacy. A sustained release dosage form is beneficial in terms of reducing the injection frequency and improving the therapeutic effectiveness. The aim of this study was to formulate a new microsphere form of a FIX-cont...

    journal_title：Molecular pharmaceutics

    pub_type： 杂志文章

    doi：10.1021/mp200133s

    authors： Chang LC,Yang CY,Chua AC,Lin YJ,Lai SM

    更新日期：2011-10-03 00:00:00

  • The biowaiver extension for BCS class III drugs: the effect of dissolution rate on the bioequivalence of BCS class III immediate-release drugs predicted by computer simulation.

    abstract：:The Biopharmaceutical Classification System (BCS) guidance issued by the FDA allows waivers for in vivo bioavailability and bioequivalence studies for immediate-release (IR) solid oral dosage forms only for BCS class I drugs. However, a number of drugs within BCS class III have been proposed to be eligible for biowaiv...

    journal_title：Molecular pharmaceutics

    pub_type： 杂志文章

    doi：10.1021/mp100053q

    authors： Tsume Y,Amidon GL

    更新日期：2010-08-02 00:00:00

  • Prediction of Response to Therapy for Autoimmune/Inflammatory Diseases Using an Activated Macrophage-Targeted Radioimaging Agent.

    abstract：:The ability to select patients who will respond to therapy is especially acute for autoimmune/inflammatory diseases, where the costs of therapies can be high and the progressive damage associated with ineffective treatments can be irreversible. In this article we describe a clinical test that will rapidly predict the ...

    journal_title：Molecular pharmaceutics

    pub_type： 杂志文章

    doi：10.1021/acs.molpharmaceut.5b00134

    authors： Kelderhouse LE,Robins MT,Rosenbalm KE,Hoylman EK,Mahalingam S,Low PS

    更新日期：2015-10-05 00:00:00

  • Treatment of breast and lung cancer cells with a N-7 benzyl guanosine monophosphate tryptamine phosphoramidate pronucleotide (4Ei-1) results in chemosensitization to gemcitabine and induced eIF4E proteasomal degradation.

    abstract：:The development of cancer and fibrotic diseases has been shown to be highly dependent on disregulation of cap-dependent translation. Binding protein eIF4E to N(7)-methylated guanosine capped mRNA has been found to be the rate-limiting step governing translation initiation, and therefore represents an attractive target...

    journal_title：Molecular pharmaceutics

    pub_type： 杂志文章

    doi：10.1021/mp300699d

    authors： Li S,Jia Y,Jacobson B,McCauley J,Kratzke R,Bitterman PB,Wagner CR

    更新日期：2013-02-04 00:00:00

  • Delayed Sequential Co-Delivery of Gefitinib and Doxorubicin for Targeted Combination Chemotherapy.

    abstract：:There are an increasing number of studies showing the order of drug presentation plays a critical role in achieving optimal combination therapy. Here, a nanoparticle design is presented using ion pairing and drug-polymer conjugate for the sequential delivery of gefitinib (Gi) and doxorubicin (Dox) targeting epidermal ...

    journal_title：Molecular pharmaceutics

    pub_type： 杂志文章

    doi：10.1021/acs.molpharmaceut.7b00669

    authors： Zhou Z,Jafari M,Sriram V,Kim J,Lee JY,Ruiz-Torres SJ,Waltz SE

    更新日期：2017-12-04 00:00:00

  • Capsid-Incorporation Strategy To Display Antigens for an Alternative Adenoviral Vector Vaccine Approach.

    abstract：:The adenovirus (Ad) is widely used as a vaccine because of its ability to induce a cellular and humoral immune response. In addition, human clinical trials have validated the safety and efficacy of Ad as a vaccine vector. The traditional approach for employing the adenovirus as vaccine is to configure the antigen gene...

    journal_title：Molecular pharmaceutics

    pub_type： 杂志文章,评审

    doi：10.1021/acs.molpharmaceut.8b00591

    authors： van Winkel CAJ,Moreno A,Curiel DT

    更新日期：2018-12-03 00:00:00

  • Attenuated Accumulation of Novel Fluorine (19F)-Labeled Bile Acid Analogues in Gallbladders of Fibroblast Growth Factor-15 (FGF15)-Deficient Mice.

    abstract：:Our work has focused on defining the utility of fluorine (19F)-labeled bile acid analogues and magnetic resonance imaging (MRI) to identify altered bile acid transport in vivo. In the current study, we explored the ability of this approach to differentiate fibroblast growth factor-15 (FGF15)-deficient from wild-type (...

    journal_title：Molecular pharmaceutics

    pub_type： 杂志文章

    doi：10.1021/acs.molpharmaceut.8b00454

    authors： Metry M,Felton J,Cheng K,Xu S,Ai Y,Xue F,Raufman JP,Polli JE

    更新日期：2018-11-05 00:00:00

  • PCPP-Adjuvanted Respiratory Syncytial Virus (RSV) sF Subunit Vaccine: Self-Assembled Supramolecular Complexes Enable Enhanced Immunogenicity and Protection.

    abstract：:PCPP, a well-defined polyphosphazene macromolecule, has been studied as an immunoadjuvant for a soluble form of the postfusion glycoprotein of respiratory syncytial virus (RSV sF), which is an attractive vaccine candidate for inducing RSV-specific immunity in mice and humans. We demonstrate that RSV sF-PCPP formulatio...

    journal_title：Molecular pharmaceutics

    pub_type： 杂志文章

    doi：10.1021/acs.molpharmaceut.7b00118

    authors： Cayatte C,Marin A,Rajani GM,Schneider-Ohrum K,Snell Bennett A,Marshall JD,Andrianov AK

    更新日期：2017-07-03 00:00:00

  • Development of High-Functionality and -Quality Lipids with RGD Peptide Ligands: Application for PEGylated Liposomes and Analysis of Intratumoral Distribution in a Murine Colon Cancer Model.

    abstract：:High-functionality and -quality (HFQ) lipids have a discrete molecular weight and good water dispersibility and can be produced by solid-phase peptide synthesis. Therefore, HFQ lipids are a promising material for the preparation of ligand-grafted PEGylated liposomes. Recently, we have reported serine-glycine repeated ...

    journal_title：Molecular pharmaceutics

    pub_type： 杂志文章

    doi：10.1021/acs.molpharmaceut.8b00476

    authors： Suga T,Kato N,Hagimori M,Fuchigami Y,Kuroda N,Kodama Y,Sasaki H,Kawakami S

    更新日期：2018-10-01 00:00:00

  • In vitro and in vivo evaluation of an innocuous drug cocktail to improve the quality of folic acid targeted nuclear imaging in preclinical research.

    abstract：:Folate receptor (FR) targeting is an attractive strategy for nuclear imaging of cancer and activated macrophages through application of folic acid radioconjugates. However, significant renal accumulation of folate radioconjugates and hence exceedingly high emission of radiation from the kidneys may mask uptake of radi...

    journal_title：Molecular pharmaceutics

    pub_type： 杂志文章

    doi：10.1021/mp300428p

    authors： Müller C,Reber J,Schlup C,Leamon CP,Schibli R

    更新日期：2013-03-04 00:00:00

  • Superparamagnetic iron oxide nanotheranostics for targeted cancer cell imaging and pH-dependent intracellular drug release.

    abstract：:Studies were conducted to develop antibody- and fluorescence-labeled superparamagnetic iron oxide nanoparticle (SPIO) nanotheranostics for magnetic resonance imaging (MRI) and fluorescence imaging of cancer cells and pH-dependent intracellular drug release. SPIO nanoparticles (10 nm) were coated with amphiphilic polym...

    journal_title：Molecular pharmaceutics

    pub_type： 杂志文章

    doi：10.1021/mp100273t

    authors： Zou P,Yu Y,Wang YA,Zhong Y,Welton A,Galbán C,Wang S,Sun D

    更新日期：2010-12-06 00:00:00

  • Block Copolymer Stereoregularity and Its Impact on Polymeric Micellar Nanodrug Delivery.

    abstract：:Stereoregularity of polymers is known to influence their physicochemical and functional properties in the bulk form. Recent studies have also provided evidence for the effect of polymer stereoregularity on the physicochemical and functional properties of their self-assembled nanostructures. Research in this area has w...

    journal_title：Molecular pharmaceutics

    pub_type： 杂志文章

    doi：10.1021/acs.molpharmaceut.6b01169

    authors： Soleymani Abyaneh H,Vakili MR,Shafaati A,Lavasanifar A

    更新日期：2017-08-07 00:00:00