4,364 results match your criteria Molecular Pharmaceutics [Journal]


Influence of melanin characteristics on drug binding properties.

Mol Pharm 2019 Apr 18. Epub 2019 Apr 18.

Melanins are biopolymers encompassing a high degree of chemical heterogeneity. Binding of small molecule drugs to ocular melanin significantly affects the ocular pharmacokinetics and it could serve as a strategy for prolonged drug retention in the eye. The influence of the structural and physical characteristics of melanins originating from different sources on their drug binding properties has not yet been methodically investigated. Read More

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http://dx.doi.org/10.1021/acs.molpharmaceut.9b00157DOI Listing

Multi-functionalized micelles facilitate intracellular doxorubicin delivery for reversing multidrug resistance of breast cancer.

Mol Pharm 2019 Apr 18. Epub 2019 Apr 18.

Intracellular doxorubicin (DOX) pumping out of cells through P-glycoprotein (P-gp) transporter lead to the reduction of intracellular DOX levels and induce multidrug resistance (MDR). A hyaluronic acid-deoxycholic acid-histidine and Pluronic F127 (PF127) mixed micellar system, named HA-DOCA-His-PF micelles, functionalized with active targeted endocytosis mediated via CD44 receptor, intracellular triggered DOX release under endosome-pH, and combined with PF127 mediated P-gp efflux inhibition was developed for sufficiently intracellular DOX delivery and MDR reversion. The DOX/HA-DOCA-His-PF drug-loaded micelles displayed endosomal pH-mediated self-assembly/disassembly characteristics, triggered DOX release under an endosomal (pH 5. Read More

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http://pubs.acs.org/doi/10.1021/acs.molpharmaceut.9b00094
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http://dx.doi.org/10.1021/acs.molpharmaceut.9b00094DOI Listing
April 2019
1 Read

Small-molecular theranostic assemblies functionalized by doxorubicin-hyaluronic acid-methotrexate prodrug for multiple tumor targeting and imaging-guided combined chemo-photothermal therapy.

Mol Pharm 2019 Apr 17. Epub 2019 Apr 17.

Due to high drug payload and minimized burden of foreign materials in the course of metabolism and excretion, carrier-free nanomedicine based on self-assembly of small-molecular therapeutic agents has attracted considerable attention in cancer therapy. However, obstacles still remained, such as lacking of targeting efficiency, poor physiological stability, and serious drug burst release. Herein we developed a self-dual-targeting prodrug conjugate by coupling methotrexate (MTX) and doxorubicin (DOX) to hyaluronic acid (HA) backbone which enveloped the small molecular drug co-assemblies of DOX and indocyanine green (ICG) for specific targeting and imaging-guided chemo-photothermal therapy (PTT). Read More

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http://dx.doi.org/10.1021/acs.molpharmaceut.9b00072DOI Listing
April 2019
1 Read

Quantifying CEACAM targeted liposome delivery using imaging flow cytometry.

Mol Pharm 2019 Apr 17. Epub 2019 Apr 17.

Carcinoembryonic antigen-like cell adhesion molecules (CEACAMs) are human cell-surface proteins that can exhibit increased expression on tumor cells, and are thus a potential target for novel tumor-seeking therapeutic delivery methods. We hypothesize that engineered nanoparticles containing a known interaction partner of CEACAM, the Neisseria gonorrhoeae outer membrane protein Opa, can be used to deliver cargo to specific cellular targets. In this study, the cell association and uptake of protein-less liposomes and Opa proteoliposomes into CEACAM-expressing cells was measured using imaging flow cytometry. Read More

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http://dx.doi.org/10.1021/acs.molpharmaceut.8b01274DOI Listing

An integrated microfluidic platform for quantifying drug permeation across biomimetic vesicle membranes.

Mol Pharm 2019 Apr 17. Epub 2019 Apr 17.

The low membrane permeability of candidate drug molecules is a major challenge in drug development and insufficient permeability is one reason for the failure of antibiotic treatment against bacteria. Quantifying drug transport across specific pathways in living systems is challenging since one typically lacks knowledge of the exact lipidome and proteome of the individual cells under investigation. Here, we quantify drug permeability across biomimetic liposome membranes, with comprehensive control over membrane composition. Read More

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http://dx.doi.org/10.1021/acs.molpharmaceut.9b00086DOI Listing

Double drug delivery using capped mesoporous silica microparticles for the effective treatment of Inflammatory Bowel Disease.

Mol Pharm 2019 Apr 16. Epub 2019 Apr 16.

Silica mesoporous microparticles loaded with both rhodamine B (S1) or hydrocortisone (S2), and capped with an olsalazine derivative, are prepared and fully characterized. Suspensions of solids S1 and S2 in water at an acidic and a neutral pH show negligible dye/drug release, yet a notable delivery took place when the reducing agent sodium dithionite is added due to a hydrolysis of an azo bond in the capping ensemble. Besides, olsalazine fragmentation induces the release of 5-aminosalicylic acid (5-ASA). Read More

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http://dx.doi.org/10.1021/acs.molpharmaceut.9b00041DOI Listing

Peptide Oligomerization Memory Effects and Their Impact on the Physical Stability of the GLP-1 Agonist Liraglutide.

Mol Pharm 2019 Apr 16. Epub 2019 Apr 16.

Peptides and proteins commonly have complex structural landscapes allowing for transformation into a wide array of species including oligomers, aggregates, and fibrils. The formation of undesirable forms including aggregates and fibrils poses serious risks from the perspective of drug development and disease. Liraglutide, a GLP-1 agonist for the treatment of diabetes, is a conjugated peptide that forms oligomers that can be stabilized by pH and organic solvents. Read More

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http://dx.doi.org/10.1021/acs.molpharmaceut.9b00106DOI Listing

PET Imaging of Platelet-Derived Growth Factor Receptor β in Colorectal Tumor Xenograft using Zirconium-89 Labeled Dimeric Affibody Molecule.

Mol Pharm 2019 Apr 15. Epub 2019 Apr 15.

Platelet-derived growth factor receptor β (PDGFRβ) is overexpressed in a variety of malignant cancers and plays critical role in tumor angiogenesis, and has been proven as a valuable target for cancer treatment. In this pilot study, a dimeric affibody molecule ZPDGFRβ, was prepared and radiolabeled with positron emission radionuclide zirconium-89 for PET imaging of colorectal tumors by targeting PDGFRβ expression in vivo. The PDGFRβ-binding capability of dimeric affibody was evaluated by flow cytometry, immunofluorescent staining and whole-body optical imaging. Read More

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http://dx.doi.org/10.1021/acs.molpharmaceut.8b01317DOI Listing
April 2019
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Poly(ethylene glycol)-block-poly(2-aminoethyl methacrylate hydrochloride)-based polyplexes as serum-tolerant nanosystems for enhanced gene delivery.

Mol Pharm 2019 Apr 15. Epub 2019 Apr 15.

PEGylation of cationic polyplexes has been used as a promising approach to enhance their stability and reduce unwanted interactions with biomolecules. However, this strategy generally has a negative effect on cellular uptake and, consequently, on transfection of target cells. In this work, we explore the impact of PEGylation on biological and physicochemical properties of poly(2-aminoethyl methacrylate) (PAMA)-based polyplexes. Read More

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http://dx.doi.org/10.1021/acs.molpharmaceut.9b00101DOI Listing

A Great Ride.

Authors:
Carston R Wagner

Mol Pharm 2018 Dec;15(12):5445

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http://dx.doi.org/10.1021/acs.molpharmaceut.8b01121DOI Listing
December 2018

Large-Scale Quantitative Comparison of Plasma Transmembrane Proteins between Two Human Blood-Brain Barrier Model Cell Lines, hCMEC/D3 and HBMEC/ciβ.

Mol Pharm 2019 Apr 15. Epub 2019 Apr 15.

AMED-CREST, Japan Agency for Medical Research and Development , 1-7-1 Otemachi , Chiyoda, Tokyo 100-0004 , Japan.

Transmembrane (TM) proteins localized at the plasma membrane, such as transporters and receptors, play important roles in regulating the selective permeability of the blood-brain barrier (BBB). The purpose of the present study was to clarify the differences in the expression levels of TM proteins in the plasma membrane between two established human BBB model cell lines, hCMEC/D3 and HBMEC/ciβ, in order to assist researchers in selecting the most appropriate cell line for particular purposes. We first confirmed that plasma membranes could be enriched sufficiently for a quantitative proteomics study by using the Plasma Membrane Protein Extraction Kit provided by BioVision with a modified protocol. Read More

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http://dx.doi.org/10.1021/acs.molpharmaceut.9b00114DOI Listing

Combined Cancer Chemo-Photodynamic and Photothermal Therapy Based on ICG/PDA/TPZ-Loaded Nanoparticles.

Mol Pharm 2019 Apr 12. Epub 2019 Apr 12.

Shanghai Key Laboratory of Functional Materials Chemistry , East China University of Science and Technology , Shanghai 200237 , China.

Although photodynamic therapy (PDT) has been an attractive strategy for several cancer treatments in the clinical setting, PDT efficacy is attenuated by consumption of oxygen. To address this photodynamic issue, we adopted a phototherapy-chemotherapy combination strategy based on targeted delivery of the near-infrared photosensitizer indocyanine green (ICG), photothermal conversion agent polydopamine (PDA), and tirapazamine (TPZ), a hypoxia-activated prodrug. Under laser irradiation, ICG consumption of oxygen and aggravated hypoxia in tumor sites can activate TPZ to damage DNA. Read More

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http://pubs.acs.org/doi/10.1021/acs.molpharmaceut.9b00119
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http://dx.doi.org/10.1021/acs.molpharmaceut.9b00119DOI Listing
April 2019
3 Reads

Organic Anion Transporting Polypeptide 1a4 (Oatp1a4/Slco1a4) at the Blood-Arachnoid Barrier is the Major Pathway of Sulforhodamine-101 Clearance from Cerebrospinal Fluid of Rats.

Mol Pharm 2019 Apr 12. Epub 2019 Apr 12.

The blood-arachnoid barrier (BAB), which is formed by arachnoid epithelial cells linked by tight junctions, has generally been considered impermeable to water-soluble substances. However, we recently demonstrated that organic anion transporters 1 and 3 (oat1, oat3) play roles in drug clearance at the BAB. Here, we examined whether organic anion-transporting polypeptide (Oatp) also plays a role, using the fluorescent organic anion sulforhodamine-101 (SR-101) as a model substrate. Read More

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http://pubs.acs.org/doi/10.1021/acs.molpharmaceut.9b00005
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http://dx.doi.org/10.1021/acs.molpharmaceut.9b00005DOI Listing
April 2019
5 Reads

Drug-Conjugated Dendrimer Hydrogel Enables Sustained Drug Release via a Self-Cleaving Mechanism.

Mol Pharm 2019 Apr 11. Epub 2019 Apr 11.

In this study, the anti-cancer drug, camptothecin (CPT), was covalently grafted onto polyamidoamine (PAMAM) dendrimer surface and then reacted with polyethylene glycol diacrylate (PEG-DA) to form dendrimer hydrogel (DH-G3-CPT) with low cross-linking density. In this novel drug delivery system, CPT was cleaved from dendrimer via the ammonolysis of ester bonds and then diffused out of the hydrogel network, thus leading to significantly prolonged drug release. The self-cleaving release kinetics of camptothecin can be further tuned by pH. Read More

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http://pubs.acs.org/doi/10.1021/acs.molpharmaceut.8b01207
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http://dx.doi.org/10.1021/acs.molpharmaceut.8b01207DOI Listing
April 2019
2 Reads

Identification of Tumor Specific Peptide as EpCAM Ligand and Its Potential Diagnostic and Therapeutic Clinical Application.

Mol Pharm 2019 Apr 18. Epub 2019 Apr 18.

Section of Thoracic Surgery, Department of Surgery , University of Michigan Medical School , Ann Arbor , Michigan 48109 , United States.

Tumor targeting agents are being developed for early tumor detection and therapeutics. We previously identified the peptide SNFYMPL (SNF*) and demonstrated its specific binding to human esophageal specimens of high-grade dysplasia (HGD) and adenocarcinoma with imaging ex vivo. Here, we aim to identify the target for this peptide and investigate its potential applications in imaging and drug delivery. Read More

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http://pubs.acs.org/doi/10.1021/acs.molpharmaceut.9b00185
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http://dx.doi.org/10.1021/acs.molpharmaceut.9b00185DOI Listing
April 2019
1 Read
4.384 Impact Factor

Highly Selective Protein Tyrosine Phosphatase Inhibitor, 2,2',3,3'-Tetrabromo-4,4',5,5'-tetrahydroxydiphenylmethane, Ameliorates Type 2 Diabetes Mellitus in BKS db Mice.

Mol Pharm 2019 Apr 18. Epub 2019 Apr 18.

CAS Key Laboratory of Experimental Marine Biology , Institute of Oceanology, Chinese Academy of Sciences , Qingdao 266071 , China.

Protein tyrosine phosphatase 1B (PTP1B) is a widely confirmed target of the type 2 diabetes mellitus (T2DM) treatment. Herein, we reported a highly specific PTP1B inhibitor 2,2',3,3'-tetrabromo-4,4',5,5'-tetrahydroxydiphenylmethane (compound 1), which showed promising hypoglycemic activity in diabetic BKS db mice. With the IC value of 2. Read More

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http://dx.doi.org/10.1021/acs.molpharmaceut.8b01106DOI Listing

A data analytics approach for rational design of nanomedicines with programmable drug release.

Mol Pharm 2019 Apr 11. Epub 2019 Apr 11.

Drug delivery vehicles can improve the functional efficacy of existing antimicrobial therapies by improving biodistribution and targeting. A critical property of such nanomedicine formulations is their ability to control the release kinetics of their payloads. The combination of (and interactions between) polymer, drug, and nanoparticle properties gives rise to nonlinear behavioral relationships and a large data space. Read More

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http://pubs.acs.org/doi/10.1021/acs.molpharmaceut.8b01272
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http://dx.doi.org/10.1021/acs.molpharmaceut.8b01272DOI Listing
April 2019
2 Reads

Reduced punch sticking propensity of acesulfame by salt formation - Role of crystal mechanical property and surface chemistry.

Mol Pharm 2019 Apr 11. Epub 2019 Apr 11.

Powder adhesion or sticking onto punches is one of the outstanding issues in pharmaceutical tablet manufacturing. We show in this work that, at comparable particle sizes, the acesulfame potassium exhibited pronouncedly reduced propensity to punch sticking than acesulfame. Detailed analyses revealed strong correlation between sticking propensity and crystal mechanical properties and surface chemistry. Read More

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http://dx.doi.org/10.1021/acs.molpharmaceut.9b00247DOI Listing

Targeted Delivery of Zoledronate To Tumor Associated Macrophages For Cancer Immunotherapy.

Mol Pharm 2019 Apr 10. Epub 2019 Apr 10.

Tumor associated macrophages (TAMs) are recruited from circulatory monocytes by tumor derived factors, which differentiate into macrophages residing in tumor microenvironment. They play critical roles in promoting angiogenesis, invasion, metastasis and immune escape and direct depletion of TAMs will be a promising strategy for tumor immunotherapy. In this study, we developed lipid coated calcium zoledronate nanoparticles (CaZol@pMNPs) containing mannose conjugation, sterically shielded with a extracellular pH sensitive material. Read More

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http://pubs.acs.org/doi/10.1021/acs.molpharmaceut.9b00261
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http://dx.doi.org/10.1021/acs.molpharmaceut.9b00261DOI Listing
April 2019
4 Reads

Tumor targeting by peptide decorated gold nanoparticles.

Mol Pharm 2019 Apr 10. Epub 2019 Apr 10.

Cancer remains one of the most important challenges in biomedical sciences. Chemotherapeutic agents are very potent molecules that exhibit a significant level of toxicity in numerous tissues of the body, particularly those characterized by high proliferative activity, such as bone marrow. The scenario is even more complex in the case of the central nervous system, and in particular brain tumors, where the blood brain barrier limits the efficacy of drug therapies. Read More

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http://dx.doi.org/10.1021/acs.molpharmaceut.9b00047DOI Listing
April 2019
1 Read

Cationic nanoliposomes are efficiently taken up by alveolar macrophages but little access dendritic cells and interstitial macrophages in the normal and CpG-stimulated lungs.

Mol Pharm 2019 Apr 9. Epub 2019 Apr 9.

The purpose of this study was to assess whether cationic nanoliposomes could address tumor vaccines to dendritic cells in the lungs in vivo. Nanoliposomes were prepared using a cationic lipid, dimethylaminoethanecarbamoyl-cholesterol (DC-cholesterol) or dioleoyltrimethylammoniumpropane (DOTAP), and dipalmitoylphosphatidylcholine (DPPC), the most abundant phospholipid in lung surfactant. The liposomes presented a size below 175 nm and they effectively entrapped tumor antigens, an oligodeoxynucletotide containing CpG motifs (CpG) and the fluorescent dye calcein used as a tracer. Read More

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http://dx.doi.org/10.1021/acs.molpharmaceut.9b00033DOI Listing

Glucan particles are a powerful adjuvant for the HBsAg, favoring antiviral immunity.

Mol Pharm 2019 Apr 9. Epub 2019 Apr 9.

The lack of vaccine adjuvants that are able to induce robust T cell responses fosters the search for more powerful options. Pathogen-like particles are a promising approach. The adjuvant activity of pathogen-like particles is highly influenced by size and surface composition. Read More

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http://dx.doi.org/10.1021/acs.molpharmaceut.8b01322DOI Listing

Synthesis and bioevaluation of novel 18FDG-conjugated 2-nitroimidazole derivatives for tumor-hypoxia imaging.

Mol Pharm 2019 Apr 9. Epub 2019 Apr 9.

Hypoxia imaging can guide tumor treatment and monitor changes in hypoxia during treatment. However, there is still no ideal hypoxia imaging agent for clinical applications. In this study, two novel 2-nitromidazole derivatives were synthesized and directly radiolabeled by [18F]FDG in high radiochemical yield and excellent radiochemical purity. Read More

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http://pubs.acs.org/doi/10.1021/acs.molpharmaceut.9b00075
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http://dx.doi.org/10.1021/acs.molpharmaceut.9b00075DOI Listing
April 2019
4 Reads

Exosomes as Drug Carriers for Cancer Therapy.

Mol Pharm 2019 Apr 16. Epub 2019 Apr 16.

Department of Pharmaceutical Sciences , North Dakota State University , Fargo , North Dakota 58105 , United States.

Exosomes, biological extracellular vesicles, have recently begun to find use in targeted drug delivery in solid tumor research. Ranging from 30-120 nm in size, exosomes are secreted from cells and isolated from bodily fluids. Exosomes provide a unique material platform due to their characteristics, including physical properties such as stability, biocompatibility, permeability, low toxicity, and low immunogenicity-all critical to the success of any nanoparticle drug delivery system. Read More

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http://dx.doi.org/10.1021/acs.molpharmaceut.9b00104DOI Listing
April 2019
3 Reads

Enhanced Delivery of Plasmid DNA to Skeletal Muscle Cells using a DLC8-Binding Peptide and ASSLNIA-Modified PAMAM Dendrimer.

Mol Pharm 2019 Apr 5. Epub 2019 Apr 5.

Skeletal muscle is ideally suited and highly desirable as a target for therapeutic gene delivery because of its abundance, high vascularization, and high levels of protein expression. However, efficient gene delivery to skeletal muscle remains a current challenge. Besides the major obstacle of cell-specific targeting, efficient intracellular trafficking, or the cytosolic transport of DNA to the nucleus, must be demonstrated. Read More

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http://dx.doi.org/10.1021/acs.molpharmaceut.8b01313DOI Listing

Application of Co-Amorphous Technology for Improving the Physicochemical Properties of Amorphous Formulations.

Mol Pharm 2019 Apr 18. Epub 2019 Apr 18.

Pharmaceutical Science & Technology Labs. , Astellas Pharma Inc. , 21, Miyukigaoka , Tsukuba-shi , Ibaraki 305-8585 , Japan.

Co-amorphous technology was recently introduced to stabilize drugs in the amorphous state for drug development. We examined the predictability of the formation of co-amorphous systems and identified two reliable indicators of successful formation: (1) a negative Δ H value and (2) small Δlog P between components. Moreover, we found that the stability of co-amorphous systems was improved when (1) Δ H was negative and (2) amorphous forms of the constituent compounds were stable. Read More

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http://dx.doi.org/10.1021/acs.molpharmaceut.9b00105DOI Listing
April 2019
1 Read

Inducible membrane permeabilization by attenuated lytic peptides: A new concept for accessing cell interiors through ruffled membranes.

Mol Pharm 2019 Apr 4. Epub 2019 Apr 4.

A variety of mid-sized and large biomolecules have been used as tools to explore fundamental biological questions. However, such molecules are often cell-impermeable and thus unable to attain sufficient access to the cell interior. This inhibits their ability to yield analytical data about the cell interior or modify the cellular events. Read More

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http://dx.doi.org/10.1021/acs.molpharmaceut.9b00156DOI Listing
April 2019
1 Read

Development of Simplified in Vitro P-Glycoprotein Substrate Assay and in Silico Prediction Models To Evaluate Transport Potential of P-Glycoprotein.

Mol Pharm 2019 Apr 16. Epub 2019 Apr 16.

Laboratory of Bioinformatics , National Institutes of Biomedical Innovation, Health and Nutrition , 7-6-8 Saito-Asagi , Ibaraki , Osaka 567-0085 , Japan.

For efficient drug discovery and screening, it is necessary to simplify P-glycoprotein (P-gp) substrate assays and to provide in silico models that predict the transport potential of P-gp. In this study, we developed a simplified in vitro screening method to evaluate P-gp substrates by unidirectional membrane transport in P-gp-overexpressing cells. The unidirectional flux ratio positively correlated with parameters of the conventional bidirectional P-gp substrate assay ( R = 0. Read More

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http://dx.doi.org/10.1021/acs.molpharmaceut.8b01143DOI Listing
April 2019
2 Reads

Enhanced Aerosolization of High Potency Nanoaggregates of Voriconazole by Dry Powder Inhalation.

Mol Pharm 2019 Apr 10. Epub 2019 Apr 10.

College of Pharmacy , The University of Texas at Austin , Austin , Texas 78712 , United States.

Invasive pulmonary aspergillosis is a deadly fungal infection with a high mortality rate, particularly in patients having undergone transplant surgery. Voriconazole, a triazole antifungal pharmaceutical product, is considered as a first-line therapy for invasive pulmonary aspergillosis, and exhibits efficacy even for patients who have failed other antifungal drug therapies. The objective of this study is to develop high potency nanoaggregates of crystalline voriconazole composition for dry powder inhalation using the particle engineering process, thin film freezing. Read More

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http://pubs.acs.org/doi/10.1021/acs.molpharmaceut.8b00907
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http://dx.doi.org/10.1021/acs.molpharmaceut.8b00907DOI Listing
April 2019
2 Reads
4.384 Impact Factor

Cryo-TEM and AFM Observation of the Time-Dependent Evolution of Amorphous Probucol Nanoparticles Formed by the Aqueous Dispersion of Ternary Solid Dispersions.

Mol Pharm 2019 Apr 9. Epub 2019 Apr 9.

Graduate School of Pharmaceutical Sciences , Chiba University , 1-8-1 Inohana, Chuo-ku , Chiba 260-8675 , Japan.

In this study, the time-dependent evolution of amorphous probucol nanoparticles was characterized by cryogenic transmission electron microscopy (cryo-TEM) and atomic force microscopy (AFM). The nanoparticles were formed by dispersing ternary solid dispersions of probucol in water. Spray drying and cogrinding were used to prepare a spray-dried sample (SPD) and two ground-mixture samples (GM(I) and GM(II)) of probucol (PBC) form I and form II/hypromellose/sodium dodecyl sulfate ternary solid dispersions. Read More

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http://pubs.acs.org/doi/10.1021/acs.molpharmaceut.9b00158
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http://dx.doi.org/10.1021/acs.molpharmaceut.9b00158DOI Listing
April 2019
2 Reads

Hyaluronan-Stabilized Redox-Sensitive Nanoassembly for Chemo-Gene Therapy and Dual T1/T2 MR Imaging in Drug-Resistant Breast Cancer Cells.

Mol Pharm 2019 Apr 15. Epub 2019 Apr 15.

Department of Biomedical Science and BK21 PLUS Center for Creative Biomedical Scientists at Chonnam National University , Chonnam National University Medical School , Gwangju 61469 , Republic of Korea.

Tailoring combinatorial therapies along with real-time monitoring strategies has been the major focus of overcoming multidrug resistance in cancer. However, attempting to develop a multifunctional nanoplatform in a single construct leads to compromising therapeutic outcomes. Herein, we developed a simple, theranostic nanoassembly containing a hyaluronic acid-stabilized redox-sensitive (HART) polyethylenimine polyplex composed of a doxorubicin (DOX) intercalated Bcl-2 shRNA encoded plasmid along with a green-synthesized hausmannite (MnO) and hematite (FeO) nanoparticle (GMF). Read More

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http://dx.doi.org/10.1021/acs.molpharmaceut.9b00189DOI Listing
April 2019
1 Read

Geometry of a TLR2-Agonist-Based Adjuvant Can Affect the Resulting Antigen-Specific Immune Response.

Mol Pharm 2019 Apr 12. Epub 2019 Apr 12.

Department of Microbiology and Immunology , The University of Melbourne, at The Peter Doherty Institute for Infection and Immunity , 792 Elizabeth Street , Melbourne , Victoria 3010 , Australia.

Targeted delivery of otherwise nonimmunogenic antigens to Toll-like receptors (TLRs) expressed on dendritic cells (DCs) has proven to be an effective means of improving immunogenicity. For this purpose, we have used a branched cationic lipopeptide, RPamCys, which is an agonist for TLR2 and enables electrostatic association with antigen for this purpose. Here, we compare the immunological properties of ovalbumin formulated with different geometrical configurations of RPamCys. Read More

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http://dx.doi.org/10.1021/acs.molpharmaceut.9b00026DOI Listing

Miniaturized Measurement of Drug-Polymer Interactions via Viscosity Increase for Polymer Selection in Amorphous Solid Dispersions.

Mol Pharm 2019 Apr 12. Epub 2019 Apr 12.

Institute of Pharmacy, Faculty of Natural Sciences I , Martin Luther University Halle-Wittenberg , Wolfgang-Langenbeck-Str. 4 , 06120 Halle/Saale , Germany.

Drug-polymer interactions have a substantial impact on stability and performance of amorphous solid dispersions (ASD) but are difficult to analyze. Whereas there are many screening methods described for polymer selection based for example on glass forming ability, drug-polymer miscibility, supersaturation, or inhibition of recrystallization, the distinct detection of physico-chemical interactions mostly lacks miniaturized techniques. This work presents an interaction screening assessing the relative viscosity increase between highly concentrated polymer solutions with and without the model drug ketoconazole (KTZ). Read More

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http://dx.doi.org/10.1021/acs.molpharmaceut.9b00186DOI Listing
April 2019
1 Read

Application of an in Vitro Blood-Brain Barrier Model in the Selection of Experimental Drug Candidates for the Treatment of Huntington's Disease.

Mol Pharm 2019 Apr 4. Epub 2019 Apr 4.

CHDI Management , CHDI Foundation , Center Drive Los Angeles 6080 , California , United States.

Huntington's disease (HD) is a neurodegenerative disease caused by polyglutamine expansion in the huntingtin protein. For drug candidates targeting HD, the ability to cross the blood-brain barrier (BBB) and reach the site of action in the central nervous system (CNS) is crucial for achieving pharmacological activity. To assess the permeability of selected compounds across the BBB, we utilized a two-dimensional model composed of primary porcine brain endothelial cells and rat astrocytes. Read More

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http://dx.doi.org/10.1021/acs.molpharmaceut.9b00042DOI Listing
April 2019
1 Read
4.384 Impact Factor

Magnetophoretic Delivery of a Tumor-Priming Agent for Chemotherapy of Metastatic Murine Breast Cancer.

Mol Pharm 2019 Apr 10. Epub 2019 Apr 10.

Department of Industrial and Physical Pharmacy , Purdue University , 575 Stadium Mall Drive , West Lafayette , Indiana 47907 , United States.

Tumor microenvironment is a significant physical barrier to the effective delivery of chemotherapy into solid tumors. To overcome this challenge, tumors are pretreated with an agent that reduces cellular and extracellular matrix densities prior to chemotherapy. However, it also comes with a concern that metastasis may increase due to the loss of protective containment. Read More

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http://dx.doi.org/10.1021/acs.molpharmaceut.8b01148DOI Listing

Rattle-Type Gold Nanorods/Porous-SiO Nanocomposites as Near-Infrared Light-Activated Drug Delivery Systems for Cancer Combined Chemo-Photothermal Therapy.

Mol Pharm 2019 Apr 4. Epub 2019 Apr 4.

School of Pharmacy , Nantong University , Nantong 226001 , China.

Rattle-type nanostructures with movable cores, porous shells, and hollow interiors have become attractive nanoplatforms in the field of nanomedicine, especially for targeted and stimuli-responsive drug delivery. In this work, rattle-type gold nanorods@void@porous-SiO (GVPS) nanocomposites were fabricated facilely using the surface-protecting etching method and exhibited high photothermal conversion efficiency. Taking advantage of the porous shell and hollow interior, the nanocomposites have abundant space for drug loading and successfully improved the drug loading capacity up to ∼19. Read More

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http://dx.doi.org/10.1021/acs.molpharmaceut.8b01298DOI Listing
April 2019
2 Reads
4.384 Impact Factor

Nanofiber Dressings Topically Delivering Molecularly Engineered Human Cathelicidin Peptides for the Treatment of Biofilms in Chronic Wounds.

Mol Pharm 2019 Apr 8. Epub 2019 Apr 8.

Biofilms of multidrug-resistant bacteria in chronic wounds pose a great challenge in wound care. Herein, we report the topical delivery of molecularly engineered antimicrobial peptides using electrospun nanofiber dressings as a carrier for the treatment of biofilms of multidrug-resistant bacteria in diabetic wounds. Molecularly engineered human cathelicidin peptide 17BIPHE2 was successfully encapsulated in the core of pluronic F127/17BIPHE2-PCL core-shell nanofibers. Read More

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http://dx.doi.org/10.1021/acs.molpharmaceut.8b01345DOI Listing

Deamidation Can Compromise Antibody Colloidal Stability and Enhance Aggregation in a pH-Dependent Manner.

Mol Pharm 2019 Apr 16. Epub 2019 Apr 16.

Isermann Department of Chemical & Biological Engineering, Center for Biotechnology & Interdisciplinary Studies , Rensselaer Polytechnic Institute , Troy , New York 12180 , United States.

Monoclonal antibodies must be both chemically and physically stable to be developed into safe and effective drugs. Although there has been considerable progress in separately understanding the molecular determinants of antibody chemical and physical stability, it remains poorly understood how defects in one property (e.g. Read More

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http://dx.doi.org/10.1021/acs.molpharmaceut.8b01311DOI Listing
April 2019
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Fenofibrate-Loaded Biodegradable Nanoparticles for the Treatment of Experimental Diabetic Retinopathy and Neovascular Age-Related Macular Degeneration.

Mol Pharm 2019 Mar 26. Epub 2019 Mar 26.

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center , Sun Yat-sen University , Guangzhou , Guangdong 510060 , China.

Fenofibrate is a peroxisome proliferator-activated receptor α (PPARα) agonist and has been shown to have therapeutic effects on diabetic retinopathy (DR). However, the effects of fenofibrate through systemic administration are not as potent as desired due to inefficient drug delivery to the retina. The present study aimed to explore the sustained therapeutic effects of fenofibrate-loaded biodegradable nanoparticles (NP) on both DR and neovascular age-related macular degeneration (AMD). Read More

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http://dx.doi.org/10.1021/acs.molpharmaceut.8b01319DOI Listing
March 2019
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Toward the Optimization of Click-Mediated Pretargeted Radioimmunotherapy.

Mol Pharm 2019 Apr 9. Epub 2019 Apr 9.

Department of Chemistry , Hunter College of the City University of New York , New York , New York 10021 , United States.

Pretargeted radioimmunotherapy (PRIT) based on the inverse electron demand Diels-Alder reaction has shown promise in murine models of disease, yet the radiation dosimetry of this approach must be optimized to make it a viable clinical option. To this end, we have leveraged two recent developments in pretargeted imaging-dendritic scaffolds and masking agents-to improve the dosimetric profile of a proof-of-concept PRIT system that is based on the huA33 antibody, a Lu-labeled tetrazine radioligand ([Lu]Lu-DOTA-PEG-Tz), and a mouse model of A33 antigen-expressing colorectal carcinoma. Pretargeting using an huA33 immunoconjugate bearing a trans-cyclooctene-decorated dendritic scaffold (huA33-DEN-TCO) produced significantly higher tumoral activity concentrations at 120 h post-injection (23. Read More

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http://dx.doi.org/10.1021/acs.molpharmaceut.9b00062DOI Listing

MRI Assessment of Prostate-Specific Membrane Antigen (PSMA) Targeting by a PSMA-Targeted Magnetic Nanoparticle: Potential for Image-Guided Therapy.

Mol Pharm 2019 Apr 10. Epub 2019 Apr 10.

The Russell H. Morgan Department of Radiology and Radiological Science , Johns Hopkins University School of Medicine , Baltimore , Maryland 21287 , United States.

Magnetic nanoparticle (MNP)-induced hyperthermia is currently being evaluated for localized prostate cancer. We evaluated the feasibility of tumor-selective delivery of prostate-specific membrane antigen (PSMA)-targeted MNPs in a murine model with high-resolution magnetic resonance imaging (MRI) after intravenous administration of MNPs at a concentration necessary for hyperthermia. A PSMA-targeted MNP was synthesized and evaluated using T-weighted MRI, after intravenous administration of 50 mg/kg of the MNP. Read More

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http://pubs.acs.org/doi/10.1021/acs.molpharmaceut.9b00036
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http://dx.doi.org/10.1021/acs.molpharmaceut.9b00036DOI Listing
April 2019
4 Reads
4.384 Impact Factor

Effects of localization of antigen proteins in antigen-loaded exosomes on efficiency of antigen presentation.

Mol Pharm 2019 Mar 25. Epub 2019 Mar 25.

Exosomes are considered to be vehicles of antigen delivery. The localization of antigen proteins, i.e. Read More

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http://dx.doi.org/10.1021/acs.molpharmaceut.8b01093DOI Listing
March 2019
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Biodegradable and pH-Responsive Acetalated Dextran (Ac-Dex) Nanoparticles for NIR Imaging and Controlled Delivery of a Platinum-Based Prodrug into Cancer Cells.

Mol Pharm 2019 Apr 1. Epub 2019 Apr 1.

Institute of Chemistry , University of Campinas-UNICAMP , 13083-970 Campinas , SP , Brazil.

Nanoparticles (NPs) based on the biodegradable acetalated dextran polymer (Ac-Dex) were used for near-infrared (NIR) imaging and controlled delivery of a Pt prodrug into cancer cells. The Ac-Dex NPs loaded with the hydrophobic Pt prodrug 3 (Pt/Ac-Dex NPs) and with the novel hydrophobic NIR-fluorescent dye 9 (NIR-dye 9/Ac-Dex NPs), as well as Ac-Dex NPs coloaded with both compounds (coloaded Ac-Dex NPs), were assembled using a single oil-in-water nanoemulsion method. Dynamic light scattering measurements and scanning electron microscopy images showed that the resulting Ac-Dex NPs are spherical with an average diameter of 100 nm, which is suitable for accumulation in tumors via the enhanced permeation and retention effect. Read More

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http://dx.doi.org/10.1021/acs.molpharmaceut.9b00058DOI Listing

In Vitro Dissolution Model Can Predict the in Vivo Taste Masking Performance of Coated Multiparticulates.

Mol Pharm 2019 Apr 1. Epub 2019 Apr 1.

UCL School of Pharmacy , 29-39 Brunswick Square , London WC1N 1AX , U.K.

The majority of active pharmaceutical ingredients (APIs) are bitter. Therefore, compliance can be a problem where adequate taste masking has not been achieved; this is most problematic in pediatrics. Taste masking is thus a key stage during pharmaceutical development with an array of strategies available to the formulation scientist. Read More

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http://dx.doi.org/10.1021/acs.molpharmaceut.9b00060DOI Listing
April 2019
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Tailored Nanocarriers for the Pulmonary Delivery of Levofloxacin against Pseudomonas aeruginosa: A Comparative Study.

Mol Pharm 2019 Apr 4. Epub 2019 Apr 4.

Cystic fibrosis (CF) patients are faced with chronic bacterial infections displaying persistent resistance if not eradicated during the first stage of the disease. Nanoantibiotics for pulmonary administration, such as liposomal ciprofloxacin or amikacin, have progressed through clinics thanks to their sustained release, prolonged lung residence time, and low systemic absorption. In this work, we sought a nanoformulation of levofloxacin for the treatment of Pseudomonas aeruginosa. Read More

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http://dx.doi.org/10.1021/acs.molpharmaceut.8b01256DOI Listing
April 2019
5 Reads

Mitochondria and Nuclei Dual-Targeted Hollow Carbon Nanospheres for Cancer Chemophotodynamic Synergistic Therapy.

Mol Pharm 2019 Apr 2. Epub 2019 Apr 2.

Cancer Metastasis Alert and Prevention Center, College of Chemistry, Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy , Fuzhou University , Fuzhou , Fujian 350116 , China.

Dual-targeted nanoparticles are gaining increasing importance as a more effective anticancer strategy by attacking double key sites of tumor cells, especially in chemophotodynamic therapy. To retain the nuclei inhibition effect and enhance doxorubicin (DOX)-induced apoptosis by mitochondrial pathways simultaneously, we synthesized the novel nanocarrier (HKH) based on hollow carbon nitride nanosphere (HCNS) modified with hyaluronic acid (HA) and the mitochondrial localizing peptide [KLAKLAK] (KLA). DOX-loaded HKH nanoparticles (HKHDs) showed satisfactory drug-loading efficiency, excellent solubility, and very low hemolytic effect. Read More

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http://dx.doi.org/10.1021/acs.molpharmaceut.9b00259DOI Listing
April 2019
2 Reads
4.384 Impact Factor

Development of the Tc-Hydroxamamide Complex as a Probe Targeting Carbonic Anhydrase IX.

Mol Pharm 2019 Apr 20;16(4):1489-1497. Epub 2019 Mar 20.

Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences , Kyoto University , 46-29 Yoshida Shimoadachi-cho, Sakyo-ku , Kyoto 606-8501 , Japan.

Carbonic anhydrase IX (CA-IX) is regarded as a favorable target for in vivo imaging because of its specific expression in hypoxic regions of tumors. Hypoxia assists tumor propagation and growth and is resistant to chemotherapy and radiotherapy. Here, we designed and synthesized [Tc]hydroxamamide ([Tc]Ham) and [Tc]methyl-substituted-hydroxamamide ([Tc]MHam) complexes including a bivalent CA-IX ligand, sulfonamide (SA), and ureidosulfonamide (UR). Read More

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http://dx.doi.org/10.1021/acs.molpharmaceut.8b01120DOI Listing

Multifunctional Nanosystem Based on Graphene Oxide for Synergistic Multistage Tumor-Targeting and Combined Chemo-Photothermal Therapy.

Mol Pharm 2019 Apr 3. Epub 2019 Apr 3.

Department of General Surgery , The Affiliated Southeast Hospital of Xiamen University , Zhangzhou 363000 , China.

Locating nanomedicines at the active sites plays a pivotal role in the nanoparticle-based cancer therapy field. Herein, a multifunctional nanotherapeutic is designed by using graphene oxide (GO) nanosheets with rich carboxyl groups as the supporter for hyaluronic acid (HA)-methotrexate (MTX) prodrug modification via an adipicdihydrazide cross-linker, achieving synergistic multistage tumor-targeting and combined chemo-photothermal therapy. As a tumor-targeting biomaterial, HA can increase affinity of the nanocarrier toward CD44 receptor for enhanced cellular uptake. Read More

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http://pubs.acs.org/doi/10.1021/acs.molpharmaceut.8b01335
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http://dx.doi.org/10.1021/acs.molpharmaceut.8b01335DOI Listing
April 2019
4 Reads
4.384 Impact Factor

Development and Evaluation of an F-Radiolabeled Monocyclam Derivative for Imaging CXCR4 Expression.

Mol Pharm 2019 Apr 3. Epub 2019 Apr 3.

Cancer Imaging Centre, Department of Surgery and Cancer, Faculty of Medicine , Imperial College London , Hammersmith Hospital Campus, Du Cane Road , London W12 0NN , U.K.

In humans, C-X-C chemokine receptor type 4 (CXCR4) is a protein that is encoded by the CXCR4 gene and binds the ligand CXCL12 (also known as SDF-1). The CXCR4-CXCL12 interaction in cancer elicits biological activities that result in tumor progression and has accordingly been the subject of significant investigation for detection and treatment of the disease. Peptidic antagonists have been labeled with a variety of radioisotopes for the detection of CXCR4, but the methodology utilizing small molecules has predominantly used radiometals. Read More

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http://dx.doi.org/10.1021/acs.molpharmaceut.9b00069DOI Listing
April 2019
1 Read