4,279 results match your criteria Molecular Pharmaceutics [Journal]


Multiple Machine Learning Comparisons of HIV Cell-Based and Reverse Transcriptase Datasets.

Mol Pharm 2019 Feb 19. Epub 2019 Feb 19.

The human immunodeficiency virus (HIV) causes over a million deaths every year and has a huge economic impact in many countries. The first class of drugs approved were nucleoside reverse transcriptase inhibitors. A newer generation of reverse transcriptase inhibitors have become susceptible to drug resistant strains of HIV, and hence alternatives are urgently needed. Read More

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http://dx.doi.org/10.1021/acs.molpharmaceut.8b01297DOI Listing
February 2019
1 Read

NIR-Light-Triggered Anticancer Strategy for Dual-Modality Imaging-Guided Combination Therapy via a Bioinspired Hybrid PLGA Nanoplatform.

Mol Pharm 2019 Feb 22. Epub 2019 Feb 22.

School of Life Science and Technology , University of Electronic Science and Technology of China , Chengdu 610054 , Sichuan , P. R. China.

A promising approach toward cancer therapy is expected to integrate imaging and therapeutic agents into a versatile nanocarrier for achieving improved antitumor efficacy and reducing the side effects of conventional chemotherapy. Herein, we designed a poly(d,l-lactic- co-glycolic acid) (PLGA)-based theranostic nanoplatform using the double emulsion solvent evaporation method (W/O/W), which is associated with bovine serum albumin (BSA) modifications, to codeliver indocyanine green (ICG), a widely used near-infrared (NIR) dye, and doxorubicin (Dox), a chemotherapeutic drug, for dual-modality imaging-guided chemo-photothermal combination cancer therapy. The resultant ICG/Dox co-loaded hybrid PLGA nanoparticles (denoted as IDPNs) had a diameter of around 200 nm and exhibited excellent monodispersity, fluorescence/size stability, and biocompatibility. Read More

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http://dx.doi.org/10.1021/acs.molpharmaceut.8b01321DOI Listing
February 2019

Evaluation of A Novel Pb-203-Labeled Lactam-Cyclized Alpha-Melanocyte-Stimulating Hormone Peptide for Melanoma Targeting.

Mol Pharm 2019 Feb 14. Epub 2019 Feb 14.

The purpose of this study is to examine the melanocortin-1 receptor (MC1R) targeting and specificity of 203Pb-DOTA-GGNle-CycMSHhex in melanoma cells and tumors to facilitate its potential therapeutic application when labeled with 212Pb. The melanocortin-1 receptor (MC1R)-specific targeting and imaging properties of 203Pb-DOTA-GGNle-CycMSHhex were determined on B16/F1 and B16/F10 murine melanoma cells, and in B16/F1 flank melanoma-, B16/F10 flank melanoma- and B16/F10 pulmonary metastatic melanoma-bearing C57 mice. 203Pb-DOTA-GGNle-CycMSHhex displayed MC1R-specific binding on B16/F1 and B16/F10 melanoma cells and tumors. Read More

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http://dx.doi.org/10.1021/acs.molpharmaceut.9b00025DOI Listing
February 2019

3β,23,28-Trihydroxy-12-oleanene 3β-caffeate from Desmodium sambuense induced neurogenesis in PC12 cells mediated by ER stress and BDNF-TrkB signalling pathways.

Mol Pharm 2019 Feb 14. Epub 2019 Feb 14.

3β,23,28-Trihydroxy-12-oleanene 3β-caffeate (compound 1) is a neuritogenic pentacyclic triterpenoid, which was isolated from Desmodium sambuense based on a PC12 cell bioassay system. Compound 1 induced neurite outgrowth dose-dependently in PC12 cells and primary cortical neurons at doses of 0.1, 0. Read More

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http://dx.doi.org/10.1021/acs.molpharmaceut.8b00939DOI Listing
February 2019

Spray-Dried Particles of Nitric Oxide-Modified Glutathione for the Treatment of Chronic Lung Infection.

Mol Pharm 2019 Feb 22. Epub 2019 Feb 22.

Sydney School of Pharmacy, Faculty of Medicine and Health , The University of Sydney , New South Wales 2006 , Australia.

Antibiotic resistance in pathogenic bacteria has emerged as a big challenge to human and animal health and significant economy loss worldwide. Development of novel strategies to tackle antibiotic resistance is of the utmost priority. In this study, we combined glutathione (GSH), a master antioxidant in all mammalian cells, and nitric oxide, a proven biofilm-dispersing agent, to produce GSNO. Read More

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http://dx.doi.org/10.1021/acs.molpharmaceut.9b00080DOI Listing
February 2019

Inflammation-Targeted Delivery of Celastrol via Neutrophil Membrane-Coated Nanoparticles in the Management of Acute Pancreatitis.

Mol Pharm 2019 Feb 21. Epub 2019 Feb 21.

Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy , Sichuan University , Chengdu 610041 , China.

Celastrol (CLT)-loaded PEG-PLGA nanoparticles (NPs/CLT) coated with neutrophil membranes (NNPs/CLT) were explored for the management of acute pancreatitis (AP). PEG-PLGA nanoparticles sized around 150 nm were proven to selectively accumulate in the pancreas in rats with AP. NNPs were found to overcome the blood-pancreas barrier and specifically distributed to the pancreatic tissues. Read More

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http://dx.doi.org/10.1021/acs.molpharmaceut.8b01342DOI Listing
February 2019
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Detecting Vulnerable Atherosclerotic Plaques by Ga-Labeled Divalent Cystine Knot Peptide.

Mol Pharm 2019 Feb 20. Epub 2019 Feb 20.

Molecular Imaging Program at Stanford (MIPS), Department of Radiology and Bio-X Program, Canary Center at Stanford for Cancer Early Detection , Stanford University , Stanford , California 94305-5484 , United States.

Integrin αβ has been considered as a promising biomarker for vulnerable atherosclerotic plaques, and it is highly expressed by those instability-associated factors, such as macrophages, vessel endothelial cells, and smooth muscle cells. Our previous study successfully showed that the Cu-labeled divalent (containing two RGD motifs) cystine knot peptide, Cu-NOTA-3-4A, had high binding affinity and specificity in targeting vulnerable carotid atherosclerotic plaques with increased αβ levels. Therefore, considering that Ga has excellent nuclear physical properties for positron emission tomography (PET), this study aimed to investigate the feasibility of using Ga-NOTA-3-4A for PET study of vulnerable atherosclerotic plaques. Read More

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http://pubs.acs.org/doi/10.1021/acs.molpharmaceut.8b01291
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http://dx.doi.org/10.1021/acs.molpharmaceut.8b01291DOI Listing
February 2019
1 Read

Proteomic Quantification of Human Blood-Brain Barrier SLC and ABC Transporters in Healthy Individuals and Dementia Patients.

Mol Pharm 2019 Feb 8. Epub 2019 Feb 8.

Centre for Applied Pharmacokinetic Research (CAPKR) , University of Manchester , Manchester M13 9PT , U.K.

The blood-brain barrier (BBB) maintains brain homeostasis by controlling traffic of molecules from the circulation into the brain. This function is predominantly dependent on proteins expressed at the BBB, especially transporters and tight junction proteins. Alterations to the level and function of BBB proteins can impact the susceptibility of the central nervous system to exposure to xenobiotics in the systemic circulation with potential consequent effects on brain function. Read More

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http://dx.doi.org/10.1021/acs.molpharmaceut.8b01189DOI Listing
February 2019
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Immuno-PET Imaging and Pharmacokinetics of an Anti-CEA scFv-based Trimerbody and Its Monomeric Counterpart in Human Gastric Carcinoma-Bearing Mice.

Mol Pharm 2019 Feb 18. Epub 2019 Feb 18.

Radiochemistry and Nuclear Imaging Group , CIC biomaGUNE , 20014 San Sebastián , Guipúzcoa , Spain.

Monoclonal antibodies (mAbs) are currently used as therapeutic agents in different types of cancer. However, mAbs and antibody fragments developed so far show suboptimal properties in terms of circulation time and tumor penetration/retention. Here, we report the radiolabeling, pharmacokinetic evaluation, and determination of tumor targeting capacity of the previously validated anti-CEA MFE23-scFv-based N-terminal trimerbody (MFE23-trimerbody), and the results are compared to those obtained for the monomeric MFE23-scFv. Read More

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http://dx.doi.org/10.1021/acs.molpharmaceut.8b01006DOI Listing
February 2019
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Novel kappa opioid receptor agonist as improved PET radiotracer: Development and in vivo evaluation.

Mol Pharm 2019 Feb 6. Epub 2019 Feb 6.

The kappa opioid receptor (KOR) is involved in depression, alcoholism and drug abuse. The current agonist radiotracer C-GR103545 is not ideal for imaging KOR due to its slow tissue kinetics in human. The aim of our project was to develop novel KOR agonist radiotracers with improved imaging properties. Read More

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http://dx.doi.org/10.1021/acs.molpharmaceut.8b01209DOI Listing
February 2019
1 Read

Cannabidiol Increases Proliferation, Migration, Tubulogenesis, and Integrity of Human Brain Endothelial Cells through TRPV2 Activation.

Mol Pharm 2019 Feb 5. Epub 2019 Feb 5.

Inserm , U1144 , Paris F-75006 , France.

The effect of cannabidiol (CBD), a high-affinity agonist of the transient receptor potential vanilloid-2 (TRPV2) channel, has been poorly investigated in human brain microvessel endothelial cells (BMEC) forming the blood-brain barrier (BBB). TRPV2 expression and its role on Ca cellular dynamics, trans-endothelial electrical resistance (TEER), cell viability and growth, migration, and tubulogenesis were evaluated in human primary cultures of BMEC (hPBMEC) or in the human cerebral microvessel endothelial hCMEC/D3 cell line. Abundant TRPV2 expression was measured in hCMEC/D3 and hPBMEC by qRT-PCR, Western blotting, nontargeted proteomics, and cellular immunofluorescence studies. Read More

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http://pubs.acs.org/doi/10.1021/acs.molpharmaceut.8b01252
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http://dx.doi.org/10.1021/acs.molpharmaceut.8b01252DOI Listing
February 2019
4 Reads

Photolytic Labeling To Quantify Peptide-Water Interactions in Lyophilized Solids.

Mol Pharm 2019 Feb 14. Epub 2019 Feb 14.

Department of Industrial and Physical Pharmacy, College of Pharmacy , Purdue University , 575 Stadium Mall Drive , West Lafayette , Indiana 47906 , United States.

Interactions of a lyophilized peptide with water and excipients in a solid matrix were explored using photolytic labeling. A model peptide "KLQ" (Ac-QELHKLQ-NHCH) was covalently labeled with NHS-diazirine (succinimidyl 4,4'-azipentanoate), and the labeled peptide (KLQ-SDA) was formulated and exposed to UV light in both solution and lyophilized solids. Solid samples contained the following excipients at a 1:400 molar ratio: sucrose, trehalose, mannitol, histidine, or arginine. Read More

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http://dx.doi.org/10.1021/acs.molpharmaceut.8b01031DOI Listing
February 2019

Self-Assembled Cationic β-Cyclodextrin Nanostructures for siRNA Delivery.

Mol Pharm 2019 Feb 19. Epub 2019 Feb 19.

Department of Physics, Bernal Institute , University of Limerick , V94 T9PX Limerick , Ireland.

Functionalized cyclodextrin molecules assemble into a wide variety of superstructures in solution, which are of interest for drug delivery and other nanomaterial and biomaterial applications. Here we use a combined simulation and experimental approach to probe the coassembly of siRNA and cationic cyclodextrin (c-CD) derivatives into a highly stable gene delivery nanostructure. The c-CD form supramolecular structures via interdigitation of their aliphatic tails, analogous to the formation of lipid bilayers and micelles. Read More

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http://dx.doi.org/10.1021/acs.molpharmaceut.8b01307DOI Listing
February 2019

Impact of Polymer Enrichment at the Crystal-Liquid Interface on Crystallization Kinetics of Amorphous Solid Dispersions.

Mol Pharm 2019 Feb 15. Epub 2019 Feb 15.

State Key Laboratory of Natural Medicines, Department of Pharmaceutics , China Pharmaceutical University , Nanjing 210009 , China.

Amorphous solid dispersions have been widely used as an effective formulation strategy in the oral delivery of poorly soluble drugs. However, one of the main challenges in the development of amorphous drugs is to maintain their physical stability. The underlying mechanism of amorphous drugs crystallized in polymeric matrices is still poorly understood. Read More

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http://dx.doi.org/10.1021/acs.molpharmaceut.8b01331DOI Listing
February 2019

Biodegradable Hyaluronic Acid Modified with Tetraglycine-l-octaarginine as a Safe Adjuvant for Mucosal Vaccination.

Mol Pharm 2019 Feb 4. Epub 2019 Feb 4.

Faculty of Pharmaceutical Sciences , Setsunan University , 45-1, Nagaotoge-cho , Hirakata , Osaka 573-0101 , Japan.

We have been investigating the potential use of polymers modified with cell-penetrating peptides as an adjuvant for mucosal vaccination and have already developed nondegradable poly( N-vinylacetamide- co-acrylic acid) (PNVA- co-AA) with which d-octaarginine, a typical cell-penetrating peptide, was grafted. Our previous murine infection experiments demonstrated that immunoglobulin G (IgG) and immunoglobulin A (IgA) were induced in systemic circulation and secreted on nasal mucosa, respectively, through 4-time nasal inoculations with a mixture of influenza viral antigens and d-octaarginine-linked PNVA- co-AA at 7-day intervals, and that immunized mice were perfectly protected from homologous virus infection. In the present study, we designed novel biodegradable polymers bearing cell-penetrating peptides from a perspective of clinical application. Read More

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http://dx.doi.org/10.1021/acs.molpharmaceut.8b01110DOI Listing
February 2019

Linear Desferrichrome-Linked Silicon-Rhodamine Antibody Conjugate Enables Targeted Multimodal Imaging of HER2 in Vitro and in Vivo.

Mol Pharm 2019 Feb 15. Epub 2019 Feb 15.

Department of Chemistry , Stony Brook University , 100 Nicolls Road , Stony Brook , New York 11790 , United States.

We report the nuclear and optical in vitro and in vivo imaging of SKOV-3 cells by targeting HER2 with a bimodal trastuzumab conjugate. Previously, we have shown that desferrichrome derivatives provide a robust and versatile radiolabeling platform for the radioisotope zirconium-89. Here, we appended silicon-rhodamine functionalized linear desferrichrome to trastuzumab. Read More

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http://dx.doi.org/10.1021/acs.molpharmaceut.8b01278DOI Listing
February 2019

Role of Endocytosis in Nanoparticle Penetration of 3D Pancreatic Cancer Spheroids.

Mol Pharm 2019 Feb 14. Epub 2019 Feb 14.

Department of Pharmaceutical Sciences, College of Pharmacy , South Dakota State University , Brookings , South Dakota 57007 , United States.

Robust deposition of extracellular matrix is a significant barrier for delivery of nanotherapeutics and small-molecule anticancer drugs to different tumors including pancreatic ductal adenocarcinoma. Here, we investigated permeation and total uptake of polystyrene nanoparticles of different diameters in 3D multicellular spheroid models of pancreatic tumors. Special attention was given to analysis of the impact of endocytic processes on nanoparticle accumulation and distribution in spheroids. Read More

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http://dx.doi.org/10.1021/acs.molpharmaceut.8b01078DOI Listing
February 2019

N-Hydroxysulfosuccinimide Esters versus Thiomers: A Comparative Study Regarding Mucoadhesiveness.

Mol Pharm 2019 Feb 18. Epub 2019 Feb 18.

The objective of the study was to compare poly(acrylic acid)- N-hydroxysulfosuccinimide reactive esters (PAA-Sulfo-NHS) and poly(acrylic acid)-cysteine conjugates (PAA-Cys) regarding their mucoadhesiveness. Polymer conjugates were synthesized in a water free environment and characterized by UV-vis spectroscopy and FTIR. Water uptake studies were performed, and the polymers were further examined for their mucoadhesive properties and cohesiveness using the rotating cylinder method. Read More

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http://pubs.acs.org/doi/10.1021/acs.molpharmaceut.8b01183
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http://dx.doi.org/10.1021/acs.molpharmaceut.8b01183DOI Listing
February 2019
3 Reads

Unprecedented behavior of (9R)-9-hydroxystearic acid loaded keratin nanoparticles on cancer cell cycle.

Mol Pharm 2019 Jan 31. Epub 2019 Jan 31.

Histone deacetylases, HDACs, have been demonstrated to play a critical role in epigenetic signaling and were found to be overexpressed in several type of cancers, therefore they represent valuable targets for anticancer therapy. 9-Hydroxystearic acid has been shown to bind the catalytic site of HDAC1, inducing G0/G1 phase cell cycle arrest and activation of p21WAF1 gene, thus promoting cells growth inhibition and differentiation in many cancer cells. Despite the (R) enantiomer of 9-hydroxystearic acid (9R) displayed promising in vitro growth-inhibitory effect on HT29 cell line, its scarce water solubility and micromolar activity require novel solutions for improving its efficacy and bioavailability. Read More

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http://dx.doi.org/10.1021/acs.molpharmaceut.8b00827DOI Listing
January 2019

The Development of a Macromolecular Analgesic for Arthritic Pain.

Mol Pharm 2019 Jan 31. Epub 2019 Jan 31.

The addictive potential of clinically-used opioids due to their direct action on the dopaminergic reward system in the brain has limited their application. In an attempt to reduce negative side effects as well as to improve the overall effectiveness of these analgesics, we have designed, synthesized, and evaluated an N-(2-hydroxypropyl)methacrylamide (HPMA)-based macromolecular prodrug of hydromorphone (HMP), a commonly used opioid. To this end, P-HMP was synthesized via RAFT polymerization and a subsequent polymer analogous reaction. Read More

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http://dx.doi.org/10.1021/acs.molpharmaceut.8b01197DOI Listing
January 2019
1 Read

Fixed Dose Combination Formulations: Multi-Layered Platforms Designed for the Management of Cardiovascular Disease.

Mol Pharm 2019 Jan 31. Epub 2019 Jan 31.

Hyperlipidaemia is considered as one of the main risk factors associated with cardiovascular diseases (CVDs). Among different lipid-lowering agents used to manage hyperlipidaemia, statins are highly prescribed for management of hyperlipidaemia with simvastatin being one of the most common. Simvastatin is susceptible to extensive metabolism by CYP450 3A4 and 3A5 which are expressed both in the liver and the gastrointestinal tract. Read More

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http://dx.doi.org/10.1021/acs.molpharmaceut.8b01068DOI Listing
January 2019
6 Reads

Predicting the Physical Stability of Amorphous Tenapanor Hydrochloride using Local Molecular Structure Analysis, Relaxation Time Constants and Molecular Modelling Sanjeev Kothari and Radha R. Vippagunta* Pharmaceutical Chemistry and Formulations, Ardelyx, 34175 Ardenwood Blvd, Fremont, CA 94555, USA. *Corresponding Author: rvippagunta@ardelyx.com; Phone :5104567717.

Mol Pharm 2019 Jan 30. Epub 2019 Jan 30.

The conformational flexibility of organic molecules introduces more structural options for crystallization to occur, but has potential complications, such as, reduced crystallization tendency and conformational polymorphism. Although, a variety of energetically similar conformers could be anticipated, it is extremely difficult to predict the crystal conformation for conformationally flexible molecules. The present study investigates differences in thermodynamic pa-rameters for the free base, c-FB and an amorphous dihydrochloride salt, a-Di-HCl, of a conformationally flexible drug substance, tenapanor (RDX5791). Read More

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http://dx.doi.org/10.1021/acs.molpharmaceut.8b00853DOI Listing
January 2019

Doxorubicin and Anti-PD-L1 Antibody Conjugated Gold Nanoparticles for Colorectal Cancer Photochemotherapy.

Mol Pharm 2019 Feb 14. Epub 2019 Feb 14.

College of Pharmacy , Keimyung University , Daegu 42601 , Republic of Korea.

Colorectal cancer (CRC) is the third leading cause of cancer-related death worldwide. The prognosis and overall survival of CRC are known to be significantly correlated with the overexpression of PD-L1. Since combination therapies can significantly improve therapeutic efficacy, we constructed doxorubicin (DOX) conjugated and anti-PD-L1 targeting gold nanoparticles (PD-L1-AuNP-DOX) for the targeted chemo-photothermal therapy of CRC. Read More

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http://dx.doi.org/10.1021/acs.molpharmaceut.8b01157DOI Listing
February 2019

Therapeutic potential of plasma proteins derived from umbilical cord blood for acute liver failure.

Mol Pharm 2019 Jan 30. Epub 2019 Jan 30.

Acute liver failure is a life-threatening condition that rapidly progresses to loss of liver function. Currently, liver transplantation is the most definitive treatment for this entity, but suitable organs are at a significant shortage. Therefore, developing a clinically viable approach to gain additional waiting time before liver transplantation can be performed remains a top clinical priority. Read More

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http://dx.doi.org/10.1021/acs.molpharmaceut.8b01108DOI Listing
January 2019
1 Read
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Developing Biologics Tablets: The Effects of Compression on the Structure and Stability of Bovine Serum Albumin and Lysozyme.

Mol Pharm 2019 Feb 18. Epub 2019 Feb 18.

Department of Pharmaceutical Chemistry , University of Kansas , 2030 Becker Drive , Lawrence , Kansas 66047 , United States.

Oral administration is advantageous compared to the commonly used parenteral administration for local therapeutic uses of biologics or mucosal vaccines, since it can specifically target the gastrointestinal (GI) tract. It offers better patient compliance, even though the general use of such a delivery route is often limited by potential drug degradation in the GI tract and poor absorption. Using bovine serum albumin (BSA) and lysozyme as two model proteins, we studied their solid-state properties, mechanical properties, and tabletability as well as effects of compaction pressure, particle size, and humidity on protein degradation. Read More

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http://dx.doi.org/10.1021/acs.molpharmaceut.8b01118DOI Listing
February 2019

Targeted and Synergic Glioblastoma Treatment: Multifunctional Nanoparticles Delivering Verteporfin as Adjuvant Therapy for Temozolomide Chemotherapy.

Mol Pharm 2019 Feb 11. Epub 2019 Feb 11.

Center of Nanotechnology and Tissue Engineering, Photobiology and Photomedicine Research Group, Department of Chemistry FFCLRP , São Paulo University , Ribeirão Preto , Brazil.

Despite advances in cancer therapies, glioblastoma multiforme treatment remains inefficient due to the brain-blood barrier (BBB) inhibitory activity and to the low temozolomide (TMZ) chemotherapeutic selectivity. To improve therapeutic outcomes, in this work we propose two strategies, (i) photodynamic therapy (PDT) as adjuvant treatment and (ii) engineering of multifunctional theranostic/targeted nanoparticles ( m-NPs) that integrate biotin as a targeting moiety with rhodamine-B as a theranostic agent in pluronic P85/F127 copolymers. These smart m-NPs can surmount the BBB and coencapsulate multiple cargoes under optimized conditions. Read More

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http://dx.doi.org/10.1021/acs.molpharmaceut.8b01001DOI Listing
February 2019

Synthesis and Aggregation of a Porphyrin-Cored Hyperbranched Polyglycidol and Its Application as a Macromolecular Photosensitizer for Photodynamic Therapy.

Mol Pharm 2019 Feb 12. Epub 2019 Feb 12.

Department of Chemistry , University of Sheffield , Sheffield S3 7HF , U.K.

Macromolecules are potentially useful delivery systems for cancer drugs, as their size allows them to utilize the enhanced permeability and retention effect (EPR), which facilitates selective delivery to (and retention within) tumors. In addition, macromolecular delivery systems can prolong circulation times as well as protect and solubilize toxic and hydrophobic drug moieties. Overall, these properties and abilities can result in an enhanced therapeutic effect. Read More

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http://dx.doi.org/10.1021/acs.molpharmaceut.8b01119DOI Listing
February 2019
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Inhibition of ABCB1 and ABCG2 at the Mouse Blood-Brain Barrier with Marketed Drugs To Improve Brain Delivery of the Model ABCB1/ABCG2 Substrate [C]erlotinib.

Mol Pharm 2019 Feb 11. Epub 2019 Feb 11.

Center for Health & Bioresources , AIT Austrian Institute of Technology GmbH , 2444 Seibersdorf , Austria.

P-Glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) are two efflux transporters at the blood-brain barrier (BBB), which effectively restrict brain distribution of diverse drugs, such as tyrosine kinase inhibitors. There is a crucial need for pharmacological ABCB1 and ABCG2 inhibition protocols for a more effective treatment of brain diseases. In the present study, seven marketed drugs (osimertinib, erlotinib, nilotinib, imatinib, lapatinib, pazopanib, and cyclosporine A) and one nonmarketed drug (tariquidar), with known in vitro ABCB1/ABCG2 inhibitory properties, were screened for their inhibitory potency at the BBB in vivo. Read More

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http://dx.doi.org/10.1021/acs.molpharmaceut.8b01217DOI Listing
February 2019
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Physiologically Based Pharmacokinetic/Pharmacodynamic Model for Caffeine Disposition in Pregnancy.

Mol Pharm 2019 Feb 11. Epub 2019 Feb 11.

Department of Drug Discovery and Development, Harrison School of Pharmacy, Pharmacy Research Building , Auburn University , Auburn , Alabama 36849 , United States.

Caffeine is the most consumed active stimulant. About 80% of pregnant women consume caffeine orally on a daily basis. Many reports indicated consumption of >200 mg caffeine during pregnancy could increase the likelihood of miscarriage. Read More

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http://pubs.acs.org/doi/10.1021/acs.molpharmaceut.8b01276
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http://dx.doi.org/10.1021/acs.molpharmaceut.8b01276DOI Listing
February 2019
3 Reads

Synthesis and Characterization of Multivalent Protein based Soluble Antigen Arrays for Juvenile Diabetes.

Mol Pharm 2019 Jan 25. Epub 2019 Jan 25.

Autoimmune diseases are believed to be highly dependent on loss of immune tolerance to self-antigens. Currently, no treatments have been successful clinically in inducing autoantigen-specific tolerance, including efforts to utilize antigen-specific immunotherapy (ASIT) to selectively correct the aberrant autoimmunity. Soluble antigen arrays (SAgAs) represent a novel autoantigen delivery system composed of a linear polymer, hyaluronic acid (HA), displaying multiple copies of conjugated autoantigen. Read More

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http://dx.doi.org/10.1021/acs.molpharmaceut.8b01250DOI Listing
January 2019

Host-guest interactions between candesartan and its prodrug candesartan cilexetil in complex with 2-hydroxypropyl-β-cyclodextrin: on the biological potency for Angiotensin II antagonism.

Mol Pharm 2019 Jan 25. Epub 2019 Jan 25.

Renin-angiotensin aldosterone system inhibitors are for a long time extensively used for the treatment of cardiovascular and renal diseases. AT1 receptor blockers (ARBs or sartans) act as antihypertensive drugs by blocking the octapeptide hormone Angiotensin II to stimulate AT1 receptors. The antihypertensive drug candesartan (CAN) is the active metabolite of candesartan cilexetil (Atacand, CC). Read More

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http://pubs.acs.org/doi/10.1021/acs.molpharmaceut.8b01212
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http://dx.doi.org/10.1021/acs.molpharmaceut.8b01212DOI Listing
January 2019
2 Reads

Snapshots of Iron Speciation: Tracking the Fate of Iron Nanoparticle Drugs via a Liquid Chromatography-Inductively Coupled Plasma-Mass Spectrometric Approach.

Mol Pharm 2019 Feb 14. Epub 2019 Feb 14.

Department of Pharmaceutical Sciences , University of Maryland School of Pharmacy , Baltimore , Maryland 21201 , United States.

Nanomedicines are nanoparticle-based therapeutic or diagnostic agents designed for targeted delivery or enhanced stability. Nanotechnology has been successfully employed to develop various drug formulations with improved pharmacokinetic characteristics, and current research efforts are focused on the development of new innovator and generic nanomedicines. Nanomedicines, which are often denoted as complex or nonbiological complex drugs, have inherently different physicochemical and pharmacokinetic properties than conventional small molecule drugs. Read More

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http://dx.doi.org/10.1021/acs.molpharmaceut.8b01215DOI Listing
February 2019
5 Reads

In Vivo Ester Hydrolysis as a New Approach in Development of Positron Emission Tomography Tracers for Imaging Hypoxia.

Mol Pharm 2019 Feb 20. Epub 2019 Feb 20.

Beijing Institute for Brain Disorders , Capital Medical University , Beijing 100069 , P. R. China.

Hypoxia is an important biochemical and physiological condition associated with uncontrolled growth of tumor. Measurement of hypoxia in tumor tissue may be useful in characterization of tumor progression and monitoring drug treatment. [F]FMISO is the most widely employed radiotracer for imaging of hypoxic tissue with positron emission tomography (PET). Read More

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http://dx.doi.org/10.1021/acs.molpharmaceut.8b01131DOI Listing
February 2019
6 Reads

Insights into the Dissolution Mechanism of Ritonavir-Copovidone Amorphous Solid Dispersions: Importance of Congruent Release for Enhanced Performance.

Mol Pharm 2019 Feb 5. Epub 2019 Feb 5.

Department of Industrial and Physical Pharmacy, College of Pharmacy , Purdue University , West Lafayette , Indiana 47907 , United States.

The aim of this study was to probe the dissolution mechanisms of amorphous solid dispersions (ASDs) of a poorly water-soluble drug formulated with a hydrophilic polymer. Ritonavir (RTV) and polyvinylpyrrolidone/vinyl acetate (PVPVA) were used as the model drug and polymer, respectively. ASDs with drug loadings (DLs) from 10 to 50 wt % were prepared by solvent evaporation. Read More

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http://pubs.acs.org/doi/10.1021/acs.molpharmaceut.8b01261
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http://dx.doi.org/10.1021/acs.molpharmaceut.8b01261DOI Listing
February 2019
22 Reads

Cell Permeable NBD Peptide-Modified Liposomes by Hyaluronic Acid Coating for the Synergistic Targeted Therapy of Metastatic Inflammatory Breast Cancer.

Mol Pharm 2019 Feb 5. Epub 2019 Feb 5.

Key Laboratory of Smart Drug Delivery, Ministry of Education (Fudan University), Department of Pharmaceutics, School of Pharmacy , Fudan University , Shanghai 200032 , China.

Chronic inflammation is closely related to the development, deterioration, and metastasis of tumors. Recently, many studies have shown that down-regulating the expression of inflammation by blocking nuclear factor-κB (NF-κB) and signal transducer and activator of transcription 3 (STAT3) pathways could significantly inhibit tumor growth and metastasis. The combined application of curcumin (CUR) and celecoxib (CXB) has been proven to exert a synergistic antitumor effect via inhibiting the activation of NF-κB and STAT3. Read More

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http://dx.doi.org/10.1021/acs.molpharmaceut.8b01123DOI Listing
February 2019
5 Reads

Polymer Nanocoating of Amorphous Drugs for Improving Stability, Dissolution, Powder Flow, and Tabletability: The Case of Chitosan-Coated Indomethacin.

Mol Pharm 2019 Feb 6. Epub 2019 Feb 6.

College of Pharmacy , University of Minnesota , Minneapolis , Minnesota 55455 , United States.

As a result of its higher molecular mobility, the surface of an amorphous drug can grow crystals much more rapidly than the bulk, causing poor stability and slow dissolution of drug products. We show that a nanocoating of chitosan (a pharmaceutically acceptable polymer) can be deposited on the surface of amorphous indomethacin by electrostatic deposition, leading to significant improvement of physical stability, wetting by aqueous media, dissolution rate, powder flow, and tabletability. The coating condition was chosen so that the positively charged polymer deposits on the negatively charged drug. Read More

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http://dx.doi.org/10.1021/acs.molpharmaceut.8b01237DOI Listing
February 2019
4 Reads

Short Peptide-Mediated Brain-Targeted Drug Delivery with Enhanced Immunocompatibility.

Mol Pharm 2019 Feb 22;16(2):907-913. Epub 2019 Jan 22.

Department of Pharmacology, School of Basic Medical Sciences & State Key Laboratory of Molecular Engineering of Polymers , Fudan University , Shanghai 200032 , P.R. China.

Peptide ligands have been exploited as versatile tools to facilitate targeted delivery of nanocarriers. However, the effects of peptide ligands on immunocompatibility and therapeutic efficacy of liposomes remain intricate. Here, a short and stable brain targeted peptide ligand D8 was modified on the surface of doxorubicin-loaded liposomes (D8-sLip/DOX), demonstrating prolonged blood circulation and lower liver distribution in comparison to the long and stable D-peptide ligand CDX-modified doxorubicin-loaded liposomes (CDX-sLip/DOX) by mitigating natural IgM absorption. Read More

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http://dx.doi.org/10.1021/acs.molpharmaceut.8b01216DOI Listing
February 2019
6 Reads
4.384 Impact Factor

Interplay of the Organic Cation Transporters OCT1 and OCT2 with the Apically Localized Export Protein MATE1 for the Polarized Transport of Trospium.

Mol Pharm 2019 Feb 18;16(2):510-517. Epub 2019 Jan 18.

Institute of Experimental and Clinical Pharmacology and Toxicology , Friedrich-Alexander-Universität Erlangen-Nürnberg , 91054 Erlangen , Germany.

The anticholinergic drug trospium is secreted into urine and, to a smaller extent, into bile. Chemically, it is an organic cation, and it is a substrate of the uptake transporters OCT1 and OCT2 as well as for the export proteins MATE1 and MATE2-K as determined in uptake studies using HEK293 cells. So far, neither MATE-mediated export nor the interplay of OCT-mediated uptake and MATE-mediated export have been investigated. Read More

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http://dx.doi.org/10.1021/acs.molpharmaceut.8b00779DOI Listing
February 2019
1 Read

Oral Delivery of Honokiol Microparticles for Nonrapid Eye Movement Sleep.

Mol Pharm 2019 Feb 17;16(2):737-743. Epub 2019 Jan 17.

School of Pharmacy and Key Laboratory of Smart Drug Delivery, Ministry of Education , Fudan University , Shanghai 201203 , China.

Honokiol (HNK) is a small-molecule lignin extracted from Magnolia Officinalis, demonstrating high potency in promoting nonrapid eye movement (NREM) sleep by modulating the benzodiazepine site of the GABA receptor. However, the clinical use of HNK in the treatment of insomnia is restricted by its extremely low oral bioavailability. In the present work, enhanced oral bioavailability of HNK was achieved by loading it into poly lactide-glycolide acid microparticles (HNK-MP). Read More

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http://dx.doi.org/10.1021/acs.molpharmaceut.8b01016DOI Listing
February 2019
3 Reads
4.384 Impact Factor

Metallo-Cubosomes: Zinc-Functionalized Cubic Nanoparticles for Therapeutic Nucleotide Delivery.

Mol Pharm 2019 Feb 1. Epub 2019 Feb 1.

School of Chemistry, Bio21 Institute , University of Melbourne , Melbourne , Victoria 3010 , Australia.

Development of an effective and potent RNA delivery system remains a challenge for the clinical application of RNA therapeutics. Herein, we describe the development of an RNA delivery platform derived from self-assembled bicontinuous cubic lyotropic liquid crystalline phases, functionalized with zinc coordinated lipids. These metallo-cubosomes were prepared from a series of novel lipidic zinc(II)-bis(dipicolylamine) (ZnBDPA)) complexes admixed with glycerol monooleate (GMO). Read More

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http://dx.doi.org/10.1021/acs.molpharmaceut.8b00890DOI Listing
February 2019
1 Read

Effect of Polymer Hydrophobicity on the Stability of Amorphous Solid Dispersions and Supersaturated Solutions of a Hydrophobic Pharmaceutical.

Mol Pharm 2019 Feb 15;16(2):682-688. Epub 2019 Jan 15.

Department of Chemistry and the Macromolecular Science & Engineering Program , The University of Michigan , Ann Arbor , Michigan 48109 , United States.

Amorphous solid dispersions of pharmaceuticals often show improved solubility over crystalline forms. However, the crystallization of amorphous solid dispersions during storage, or from elevated supersaturation once dissolved, compromise the solubility advantage of delivery in the amorphous phase. To combat this phenomenon, polymer additives are often included in solid dispersions to inhibit crystallization; however, the optimal properties for polymer to stabilize against crystallization are not fully understood, and furthermore, it is not known how inhibition of precipitation from solution is related to the propensity of a polymer to inhibit crystallization from the amorphous phase. Read More

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http://dx.doi.org/10.1021/acs.molpharmaceut.8b00972DOI Listing
February 2019
1 Read

Use of PBPK Modeling To Evaluate the Performance of Dissolv It, a Biorelevant Dissolution Assay for Orally Inhaled Drug Products.

Mol Pharm 2019 Feb 15. Epub 2019 Feb 15.

King's College London , Institute of Pharmaceutical Science , London SE1 9NH , U.K.

The dissolution of inhaled drug particles in the lungs is a challenge to model using biorelevant methods in terms of (i) collecting a respirable emitted aerosol fraction and dose, (ii) presenting this to a small volume of medium that is representative of lung lining fluid, and (iii) measuring the low concentrations of drug released. We report developments in methodology for each of these steps and utilize mechanistic in silico modeling to evaluate the in vitro dissolution profiles in the context of plasma concentration-time profiles. The PreciseInhale aerosol delivery system was used to deliver Flixotide aerosol particles to Dissolv It apparatus for measurement of dissolution. Read More

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http://dx.doi.org/10.1021/acs.molpharmaceut.8b01200DOI Listing
February 2019
2 Reads

Evaluation Efficacy of Rhenium-188-Loaded Micro-particles for Radiotherapy in a Mouse Model of Hepatocellular Carcinoma.

Mol Pharm 2019 Feb 1. Epub 2019 Feb 1.

Department of Internal Medicine , National Cheng Kung University , Tainan 704 , Taiwan.

Hepatocellular carcinoma (HCC) is one of the leading causes of mortality worldwide. The aim of the present study was to evaluate the distribution and the therapeutic effect of Re-Tin-colloid micro-particles in subcutaneous HCC-bearing mice. The synthesis and characterization of micro-particles labeled with the Re isotope were performed. Read More

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http://dx.doi.org/10.1021/acs.molpharmaceut.8b01083DOI Listing
February 2019
1 Read

Sulfonamide-Derived Four-Component Molecular Hybrids as Novel DNA-Targeting Membrane Active Potentiators against Clinical Escherichia coli.

Mol Pharm 2019 Jan 30. Epub 2019 Jan 30.

Institute of Bioorganic & Medicinal Chemistry, Key Laboratory of Applied Chemistry of Chongqing Municipality, School of Chemistry and Chemical Engineering , Southwest University , Chongqing 400715 , China.

Novel sulfonamide-based four-component molecular hybrids as potential DNA-targeting antimicrobial agents were developed from marketed acetanilide through convenient procedures. Biological assays indicated that a few of the target compounds showed significant inhibitory efficiencies toward the tested bacteria and fungi. Noticeably, metronidazole hybrid 6a exhibited a lower minimum inhibitory concentration (MIC) value of 0. Read More

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http://dx.doi.org/10.1021/acs.molpharmaceut.8b01021DOI Listing
January 2019
3 Reads

Improved Immuno-PET Imaging of HER2-Positive Tumors in Mice: Urokinase Injection-Triggered Clearance Enhancement of Cu-Trastuzumab.

Mol Pharm 2019 Jan 30. Epub 2019 Jan 30.

Molecular Network Control Imaging Unit , RIKEN Center for Life Science Technologies , 6-7-3 Minatojima-Minamimachi , Chuo-ku, Kobe , Hyogo 650-0047 , Japan.

Immuno-positron emission tomography (immuno-PET) is expected to improve the specificity of small chemical tracers such as F-fluorodeoxyglucose. Whole antibodies significantly accumulate in target molecule-expressing tumors but frequently persist too long in the blood circulation for imaging purposes. We investigated the utility of whole antibodies, Cu-labeled via a urokinase-substrate linker, and their exogenous urokinase-responsive cleavage to enhance clearance of immuno-PET probes from the blood and shorten the time required to develop adequate imaging contrast. Read More

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http://pubs.acs.org/doi/10.1021/acs.molpharmaceut.8b01052
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http://dx.doi.org/10.1021/acs.molpharmaceut.8b01052DOI Listing
January 2019
4 Reads

Transport of the Ruthenium Complex [Ru(GA)(dppe)]PF into Triple-Negative Breast Cancer Cells Is Facilitated by Transferrin Receptors.

Mol Pharm 2019 Jan 25. Epub 2019 Jan 25.

Campus of Exact Sciences and Technology (CCET) , State University of Goiás , CEP 75132-903 Anápolis , GO , Brazil.

The triple-negative breast cancer subtype (TNBC) is highly aggressive and metastatic and corresponds to 15-20% of diagnosed cases. TNBC treatment is hampered, because these cells usually do not respond to hormonal therapy, and they develop resistance to chemotherapeutic drugs. On the other hand, the severe side effects of cisplatin represent an obstacle for its clinical use. Read More

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http://pubs.acs.org/doi/10.1021/acs.molpharmaceut.8b01154
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http://dx.doi.org/10.1021/acs.molpharmaceut.8b01154DOI Listing
January 2019
8 Reads

In Vitro Cytotoxicity and Interaction of Noscapine with Human Serum Albumin: Effect on Structure and Esterase Activity of HSA.

Mol Pharm 2019 Jan 31. Epub 2019 Jan 31.

Biophysical Chemistry Laboratory, Centre for Interdisciplinary Research in Basic Sciences , Jamia Millia Islamia (A Central University) , New Delhi 110025 , India.

Noscapine is effective to inhibit cellular proliferation and induced apoptosis in nonsmall cell, lung, breast, lymphoma, and prostate cancer. It also shows good efficiency to skin cancer cells. In the current work, we studied the mechanism of interaction between the anticancer drug noscapine (NOS) and carrier protein human serum albumin (HSA) by using a variety of spectroscopic techniques (fluorescence spectroscopy, time-resolved fluorescence, UV-visible, fluorescence resonance energy transfer (FRET), Fourier transform infrared (FTIR), and circular dichroism (CD) spectroscopy), electrochemistry (cyclic voltammetry), and computational methods (molecular docking and molecular dynamic simulation). Read More

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http://pubs.acs.org/doi/10.1021/acs.molpharmaceut.8b00864
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http://dx.doi.org/10.1021/acs.molpharmaceut.8b00864DOI Listing
January 2019
9 Reads
4.384 Impact Factor

Fluorescent Penetration Enhancers Reveal Complex Interactions among the Enhancer, Drug, Solvent, and Skin.

Mol Pharm 2019 Feb 24;16(2):886-897. Epub 2019 Jan 24.

Skin penetration/permeation enhancers facilitate drug delivery through the skin barrier. However, the specific mechanisms that govern the enhancer interactions with the skin, drug, and donor solvent are not fully understood. We designed and synthesized fluorescent-labeled enhancers by attaching 7-nitrobenzo[c][1,2,5]oxadiazol-4-yl (NBD) groups to 6-aminohexanoic acid esters. Read More

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http://dx.doi.org/10.1021/acs.molpharmaceut.8b01196DOI Listing
February 2019
1 Read

Lipolysis-Permeation Setup for Simultaneous Study of Digestion and Absorption in Vitro.

Mol Pharm 2019 Jan 29. Epub 2019 Jan 29.

Department of Pharmacy , Uppsala University , Uppsala Biomedical Center , P.O. Box 580, SE-751 23 Uppsala , Sweden.

Lipid-based formulations (LBFs) are a delivery strategy to enhance intestinal absorption of poorly water-soluble drugs. LBF performance is typically evaluated by in vitro lipolysis studies, but these do not accurately predict the in vivo performance. One possible reason is the absence of an absorptive membrane driving sink conditions in the serosal compartment. Read More

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http://dx.doi.org/10.1021/acs.molpharmaceut.8b00811DOI Listing
January 2019
2 Reads

Delivery of Doxorubicin from Hyaluronic Acid-Modified Glutathione-Responsive Ferrocene Micelles for Combination Cancer Therapy.

Mol Pharm 2019 Jan 25. Epub 2019 Jan 25.

Institute of Nervous System Diseases , Xuzhou Medical University , Xuzhou 221002 , P.R. China.

A combination of different chemotherapy approaches can obtain the best response for many cancers. However, the greatest challenge is the development of a nanoparticle formulation that can encapsulate different chemotherapeutic agents to achieve the proper synergetic chemotherapy for the tumor. Here, amphiphilic ferrocenium-tetradecyl (Fe-C) was constructed to form cationic micelles in an aqueous solution via self-assembly. Read More

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http://pubs.acs.org/doi/10.1021/acs.molpharmaceut.8b00862
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http://dx.doi.org/10.1021/acs.molpharmaceut.8b00862DOI Listing
January 2019
6 Reads