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European Journal of Pharmaceutics and Biopharmaceutics

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https://www.readbyqxmd.com/read/28807819/carrier-characteristics-influence-the-kinetics-of-passive-drug-loading-into-lipid-nanoemulsions
#1
Katrin Göke, Heike Bunjes
Passive loading as a novel screening approach is a material-saving tool for the efficient selection of a suitable colloidal lipid carrier system for poorly water soluble drug candidates. This method comprises incubation of preformed carrier systems with drug powder and subsequent determination of the resulting drug load of the carrier particles after removal of excess drug. For reliable routine use and to obtain meaningful loading results, information on the kinetics of the process is required. Passive loading proceeds via a dissolution-diffusion based mechanism, where drug surface area and drug water solubility are key parameters for fast passive loading...
August 11, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28807818/novel-concentrated-water-in-oil-emulsions-based-on-a-non-ionic-silicone-surfactant-appealing-application-properties-and-tuneable-viscoelasticity
#2
Lisa Binder, Johannes Jatschka, Dieter Baurecht, Michael Wirth, Claudia Valenta
Silicone excipients are non-irritating ingredients that are extensively used in topical formulations. In the present study, innovative water-in-oil emulsions with a high water content stabilised by a non-ionic silicone surfactant were developed. Effects of formulation composition on its properties and stability were investigated. It was possible to prepare highly stable emulsions with a water volume fraction of up to 80%. The emulsions exhibited desirable application properties such as non-sticky and cooling qualities...
August 11, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28780276/uv-imaging-of-multiple-unit-pellet-system-mups-tablets-a-case-study-of-acetylsalicylic-acid-stability
#3
Anna Novikova, Jens M Carstensen, Thomas Rades, Claudia S Leopold
The applicability of multispectral ultraviolet (UV) imaging in combination with multivariate image analysis was investigated to monitor API degradation within multiple unit pellet system (MUPS) tablets during storage. For this purpose, acetylsalicylic acid (ASA) layered pellets were coated with Eudragit(®) RL PO and compressed to MUPS tablets. These tablets were stored under four different conditions with different levels of relative humidity (0 and 75%) and temperature (21 and 40 °C) and analysed at seven storage time points (0, 15, 40, 140, 165, 265, and 330 d)...
August 2, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28780275/inhalable-sirna-loaded-nano-embedded-microparticles-engineered-using-microfluidics-and-spray-drying
#4
Monica Agnoletti, Adam Bohr, Kaushik Thanki, Feng Wan, Xianghui Zeng, Johan Peter Boetker, Mingshi Yang, Camilla Foged
Medicines based on small interfering RNA (siRNA) are promising for the treatment of a number of lung diseases. However, efficient delivery systems and design of stable dosage forms are required for inhalation therapy, as well as cost-effective methods for manufacturing of the final product. In this study, a 3D-printed micromixer was used for preparation of siRNA-dendrimer nanocomplexes, which were subsequently processed into microparticle-based dry powders for inhalation using spray drying. By applying the disposable micromixer, nanocomplexes were prepared of an average hydrodynamic diameter comparable to that of nanocomplexes prepared by manual mixing, but with narrower size distribution and low batch-to-batch variation...
August 2, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28760448/progesterone-lipid-nanoparticles-scaling-up-and-in-vivo-human-study
#5
Elisabetta Esposito, Maddalena Sguizzato, Markus Drechsler, Paolo Mariani, Federica Carducci, Claudio Nastruzzi, Rita Cortesi
This investigation describes a scaling up study aimed at producing progesterone containing nanoparticles in a pilot scale. Particularly hot homogenization techniques based on ultrasound homogenization or high pressure homogenization have been employed to produce lipid nanoparticles constituted of tristearin or tristearin in association with caprylic-capric triglyceride. It was found that the high pressure homogenization method enabled to obtain nanoparticles without agglomerates and smaller mean diameters with respect to ultrasound homogenization method...
July 28, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28756280/engineering-of-small-interfering-rna-loaded-lipidoid-poly-dl-lactic-co-glycolic-acid-hybrid-nanoparticles-for-highly-efficient-and-safe-gene-silencing-a-quality-by-design-based-approach
#6
Kaushik Thanki, Xianghui Zeng, Sarah Justesen, Sarah Tejlmann, Emily Falkenberg, Elize Van Driessche, Hanne Mørck Nielsen, Henrik Franzyk, Camilla Foged
Safety and efficacy of therapeutics based on RNA interference, e.g., small interfering RNA (siRNA), are dependent on the optimal engineering of the delivery technology, which is used for intracellular delivery of siRNA to the cytosol of target cells. We investigated the hypothesis that commonly used and poorly tolerated cationic lipids might be replaced with more efficacious and safe lipidoids as the lipid component of siRNA-loaded lipid-polymer hybrid nanoparticles (LPNs) for achieving more efficient gene silencing at lower and safer doses...
July 26, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28738178/corrigendum-to-a-glucose-targeted-mixed-micellar-formulation-outperforms-genexol-in-breast-cancer-cells-euro-j-pharmaceut-biopharmaceut-114-2017-305-316
#7
Marcela A Moretton, Ezequiel Bernabeu, Estefanía Grotz, Lorena Gonzalez, Marcela Zubillaga, Diego A Chiappetta
No abstract text is available yet for this article.
July 26, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28754262/a-comparison-of-three-peyer-s-patch-m-like-cell-culture-models-particle-uptake-bacterial-interaction-and-epithelial-histology
#8
Tauseef Ahmad, Martina Gogarty, Edwin Walsh, David J Brayden
Intestinal Peyer's patch (PP) microfold (M) cells transport microbes and particulates across the follicle-associated epithelium (FAE) as part of the mucosal immune surveillance system. In vitro human M-like cell co-culture models are used as screens to investigate uptake of antigens-in-nanoparticles, but the models are labour-intensive and there is inter-laboratory variability. We compared the three most established filter-grown Caco-2/Raji B cell co-culture systems. These were Model A (Kerneis et al, 1997), Model B (Gullberg et al...
July 25, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28754261/elucidating-the-weak-protein-protein-interaction-mechanisms-behind-the-liquid-liquid-phase-separation-of-a-mab-solution-by-different-types-of-additives
#9
Guoliang Wu, Shujing Wang Co-First, Zhou Tian, Ning Zhang, Han Sheng, Weiguo Dai, Feng Qian
Liquid-liquid phase separation (LLPS) has long been observed during the physical stability investigation of therapeutic protein formulations. The buffer conditions and the presence of various excipients are thought to play important roles in the formulation development of monoclonal antibodies (mAbs). In this study, the effects of several small-molecule excipients (histidine, alanine, glycine, sodium phosphate, sodium chloride, sorbitol and sucrose) with diverse physical-chemical properties on LLPS of a model IgG1 (JM2) solutions were investigated by multiple techniques, including UV-vis spectroscopy, circular dichroism, differential scanning calorimetry/fluorimetry, size exclusion chromatography and dynamic light scattering...
July 25, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28743595/the-film-tells-the-story-physical-chemical-characteristics-of-igg-at-the-liquid-air-interface
#10
Ellen Koepf, Rudolf Schroeder, Gerald Brezesinski, Wolfgang Friess
The presence of liquid-air interfaces in protein pharmaceuticals is known to negatively impact product stability. Nevertheless, the mechanisms behind interface-related protein aggregation are not yet fully understood. Little is known about the physical-chemical behavior of proteins adsorbed to the interface. Therefore, the combinatorial use of appropriate surface-sensitive analytical methods such as Langmuir trough experiments, Infrared Reflection-Absorption Spectroscopy (IRRAS), Brewster Angle Microscopy (BAM), and Atomic Force Microscopy (AFM) is highly expedient to uncover structures and events at the liquid-air interface directly...
July 22, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28743594/rhamnolipids-as-epithelial-permeability-enhancers-for-macromolecular-therapeutics
#11
Diego Romano Perinelli, Driton Vllasaliu, Giulia Bonacucina, Benedetta Come, Stefania Pucciarelli, Massimo Ricciutelli, Marco Cespi, Rosangela Itri, Francesco Spinozzi, Giovanni Filippo Palmieri, Luca Casettari
The use of surfactants as drug permeability enhancers across epithelial barriers remains a challenge. Although many studies have been performed in this field using synthetic surfactants, the possibility of employing surfactants produced by bacteria (the so called biosurfactants") has not been completely explored. Among them, one of the most well characterized class of biosurfactants are rhamnolipids. The aim of the study was to investigate the effect of rhamnolipids on the epithelial permeability of fluorescein isothiocyanate-labelled dextrans 4kDa and 10kDa (named FD4 and FD10, respectively) as model for macromolecular drugs, across Caco-2 and Calu-3 monolayers...
July 22, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28739288/recent-advances-on-extracellular-vesicles-in-therapeutic-delivery-challenges-solutions-and-opportunities
#12
REVIEW
Mei Lu, Haonan Xing, Zhen Yang, Yanping Sun, Tianzhi Yang, Xiaoyun Zhao, Cuifang Cai, Dongkai Wang, Pingtian Ding
Extracellular vesicles (EVs) are intrinsic mediators of intercellular communication in our body, allowing functional transfer of biomolecules (lipids, proteins, and nucleic acid) between diverse locations. Such an instrumental role evokes a surge of interest within the drug delivery community in tailoring EVs for therapeutic delivery. These vesicles represent a novel generation of drug delivery systems, providing high delivery efficiency, intrinsic targeting properties, and low immunogenicity. In the recent years, considerable research efforts have been directed toward developing safe and efficient EV-based delivery vehicles...
July 21, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28736333/synthesis-and-characterization-of-a-multifunctional-gold-doxorubicin-nanoparticle-system-for-ph-triggered-intracellular-drug-release
#13
Ganesh V Khutale, Alan Casey
A nanoparticle drug carrier system has been developed to alter the cellular uptake and chemotherapeutic performance of an available chemotherapeutic drug. The system comprises of a multifunctional gold nanoparticle based drug delivery system (Au-PEG-PAMAM-DOX) as a novel platform for intracellular delivery of doxorubicin (DOX). Spherical gold nanoparticles were synthesized by a gold chloride reduction, stabilized with thiolated polyethylene glycol (PEG) and then covalently coupled with a polyamidoamine (PAMAM) G4 dendrimer...
July 20, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28729179/global-regression-model-for-moisture-content-determination-using-near-infrared-spectroscopy
#14
Matthieu Clavaud, Yves Roggo, Klara Degardin, Pierre-Yves Sacré, Philippe Hubert, Eric Ziemons
Near-infrared (NIR) global quantitative models were evaluated for the moisture content (MC) determination of three different freeze-dried drug products. The quantitative models were based on 3822 spectra measured on two identical spectrometers to include variability. The MC, measured with the reference Karl Fischer (KF) method, were ranged from 0.05% to 4.96%. Linear and non-linear regression models using Partial Least Square (PLS), Decision Tree (DT), Bayesian Ridge Regression (Bayes-RR), K-Nearest Neighbors (KNN), and Support Vector Regression (SVR) algorithms were created and evaluated...
July 17, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28720487/pdms-b-pmoxa-polymersomes-for-hepatocyte-targeting-and-assessment-of-toxicity
#15
Klara Kiene, Susanne H Schenk, Fabiola Porta, Alexandra Ernst, Dominik Witzigmann, Philip Grossen, Jörg Huwyler
Nanoparticles, such as polymersomes, can be directed to the hepatic asialoglycoprotein receptor to achieve targeted drug delivery. In this study, we prepared asialofetuin conjugated polymersomes based on the amphiphilic di-block copolymer poly(dimethylsiloxane)-b-poly(2-methyloxazoline) (PDMS-b-PMOXA). They had an average diameter of 150nm and formed monodisperse vesicles. Drug encapsulation and sustained release was monitored using the hydrophilic model compound carboxyfluorescein. Asialoglycoprotein receptor specific uptake by HepG2 cells in vitro was energy dependent and could be competitively inhibited by the free targeting ligand...
July 15, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28713018/effect-of-increased-surface-hydrophobicity-via-drug-conjugation-on-the-clearance-of-inhaled-pegylated-polylysine-dendrimers
#16
Shadabul Haque, Victoria M McLeod, Seth Jones, Sandy Fung, Michael Whittaker, Michelle McIntosh, Colin Pouton, David J Owen, Christopher J H Porter, Lisa M Kaminskas
PEGylated polylysine dendrimers are attractive and well tolerated inhalable drug delivery platforms that have the potential to control the release, absorption kinetics and lung retention time of conjugated drugs. The clinical application of these systems though, would likely require partial substitution of surface PEG groups with drug molecules that are anticipated to alter their lung clearance kinetics and clearance pathways. In the current study, we therefore evaluated the impact of increased surface hydrophobicity via substitution of 50% surface PEG groups with a model hydrophobic drug (α-carboxyl OtButylated methotrexate) on the lung clearance of a Generation 5 PEGylated polylysine dendrimer in rats...
July 13, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28709903/targeted-delivery-of-cyclosporine-a-by-polymeric-nanocarriers-improves-the-therapy-of-inflammatory-bowel-disease-in-a-relevant-mouse-model
#17
Ana Melero, Christina Draheim, Steffi Hansen, Elisa Giner, Juan José Carreras, Raquel Talens-Visconti, Teresa María Garrigues, José Esteban Peris, Ma Carmen Recio, Rosa Giner, Claus-Michael Lehr
The therapy of inflammatory bowel diseases is still rather inefficient, and about 80% of patients require surgery at some stage. Improving the treatments by more efficient medication is, therefore, an urgent medical need. The objective of this project was to demonstrate targeted delivery of Cyclosporine-A (CYA) to the inflamed areas of the intestinal mucosa after oral administration, enabling improved alleviation of the symptoms and, at the same time, reduced systemic drug absorption and associated adverse effects...
July 11, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28694161/cxcr4-targeted-dendrimer-for-anti-cancer-drug-delivery-and-breast-cancer-cell-migration-inhibition
#18
Chuda Chittasupho, Songyot Anuchapreeda, Narong Sarisuta
CXCR4 and its ligand CXCL12 play a critical role in the metastasis of various types of cancer including breast cancer. Breast tumors preferentially metastasize to the lung, bones and distant lymph nodes, secreting high levels of CXCL12. We hypothesized that targeted inhibition of CXCR4 in breast cancer cells should suppress CXCR4-positive tumor cells toward secondary metastatic sites. In the present study, the efficacy of CXCR4 targeted dendrimers carrying DOX (LFC131-DOX-D4) on cellular binding, cytotoxicity, and migration of BT-549-Luc and T47D breast cancer cells was investigated...
July 7, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28694160/artificial-neural-network-based-particle-size-prediction-of-polymeric-nanoparticles
#19
John Youshia, Mohamed Ehab Ali, Alf Lamprecht
Particle size of nanoparticles and the respective polydispersity are key factors influencing their biopharmaceutical behavior in a large variety of therapeutic applications. Predicting these attributes would skip many preliminary studies usually required to optimize formulations. The aim was to build a mathematical model capable of predicting the particle size of polymeric nanoparticles produced by a pharmaceutical polymer of choice. Polymer properties controlling the particle size were identified as molecular weight, hydrophobicity and surface activity, and were quantified by measuring polymer viscosity, contact angle and interfacial tension, respectively...
July 7, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28690201/neurotensin-receptor-1-facilitates-intracellular-and-transepithelial-delivery-of-macromolecules
#20
Joanna L Bird, Rachael Simpson, Driton Vllasaliu, Alan D Goddard
G protein-coupled receptors are expressed on the surface of eukaryotic cells and internalise in response to ligand binding. The actions of the hormone and neurotransmitter neurotensin (NT) are predominantly mediated by specific interactions with one such receptor. Neurotensin receptor 1 (NTS1), which is upregulated in a variety of cancers, including pancreatic and breast tumours. NTS1 could therefore serve as a target for selective delivery of therapeutics. This study characterised the expression of NTS1 in HEK293 cells, as well as both polarised and non-polarised intestinal epithelial Caco-2 cells...
July 6, 2017: European Journal of Pharmaceutics and Biopharmaceutics
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