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Vaibhav Jain, Prabal K Maiti, Prasad V Bharatam
Computational studies performed on dendrimer-drug complexes usually consider 1:1 stoichiometry, which is far from reality, since in experiments more number of drug molecules get encapsulated inside a dendrimer. In the present study, molecular dynamic (MD) simulations were implemented to characterize the more realistic molecular models of dendrimer-drug complexes (1:n stoichiometry) in order to understand the effect of high drug loading on the structural properties and also to unveil the atomistic level details...
September 28, 2016: Journal of Chemical Physics
Kłosińska-Szmurło Ewa, Mazurek Aleksander Paweł, Grudzień Monika, Betlejewska-Kielak Katarzyna
BACKGROUND: Two main factors, which have an influence on oral absorption from solid, immediate release dosage form, are solubility and permeability. These are considered the main fundamental properties that govern the rate and extent of oral absorption. The significance of these properties has been highlighted in the Biopharmaceutics Classification System (BCS). OBJECTIVE: The concept of this paper was to predict the solubility and permeability of fluoroquinolones using in silico methods based on the assumptions of the BCS...
October 14, 2016: Current Computer-aided Drug Design
Theodora Karamanidou, Vassilis Bourganis, Olga Kammona, Costas Kiparissides
Biopharmaceutics have been recognized as the drugs of choice for the treatment of several diseases, mainly due to their high selectivity and potent action. Nonetheless, their oral administration is a rather challenging problem, since their bioavailability is significantly hindered by various physiological barriers along the GI tract, including their acid-induced hydrolysis in the stomach, their enzymatic degradation throughout the GI tract and their poor mucosa permeability. Lipid-based nanocarriers represent a viable means for enhancing the oral bioavailability of biomolecules while diminishing toxicity-related issues...
October 26, 2016: Nanomedicine
Simone Hansmann, Adam Darwich, Alison Margolskee, Leon Aarons, Jennifer Dressman
OBJECTIVES: The aim of this study was (1) to determine how closely physiologically based pharmacokinetic (PBPK) models can predict oral bioavailability using a priori knowledge of drug-specific properties and (2) to examine the influence of the biopharmaceutics classification system class on the simulation success. METHODS: Simcyp Simulator, GastroPlus(™) and GI-Sim were used. Compounds with published Biowaiver monographs (bisoprolol (BCS I), nifedipine (BCS II), cimetidine (BCS III), furosemide (BCS IV)) were selected to ensure availability of accurate and reproducible data for all required parameters...
October 26, 2016: Journal of Pharmacy and Pharmacology
Jaime A Cardona-Ospina, Juan C Sepúlveda-Arias, L Mancilla, Luis G Gutierrez-López
Plant expression systems could be used as biofactories of heterologous proteins that have the potential to be used with biopharmaceutical aims and vaccine design. This technology is scalable, safe and cost-effective and it has been previously proposed as an option for vaccine and protein pharmaceutical development in developing countries. Here we present a proposal of how plant expression systems could be used to address Zika and chikungunya outbreaks through development of vaccines and rapid diagnostic kits...
2016: F1000Research
Evan A Dubiel, Bruno Martin, Sylvain Vigier, Patrick Vermette
A quartz crystal microbalance (QCM) was constructed to assess if such a biosensor has value as a complementary real-time label-free analysis platform for the biopharmaceutical industry. This was achieved through modifying QCM crystals with a low-fouling carboxymethyl-dextran layer bearing Protein A, and then injecting solutions containing Etanercept (i.e., Enbrel(®)) into the QCM chambers. The kinetics of Enbrel(®) - Protein A interactions was modeled using the Langmuir binding model and Enbrel(®) concentrations between 0...
October 19, 2016: Colloids and Surfaces. B, Biointerfaces
Lauren Platts, Samuel J Darby, Robert J Falconer
The positively charged amino acids are commonly used excipients in biopharmaceutical formulations for stabilization of therapeutic proteins, yet the mechanisms for their modulation of protein stability are poorly understood. In this study, both lysine and histidine are shown to affect the thermal stability of myoglobin, bovine serum albumin, and lysozyme through a combination of mechanisms governed by their respective functional side chains and glycine, similar to arginine. This study provides evidence that at low concentrations, lysine and histidine interact with proteins by a combination of (1) direct electrostatic interactions with negatively charged side chains, (2) possible binding to high-affinity hydrophobic binding sites, and (3) glycine-mediated weak interactions with peptide backbone and polar side chains...
October 21, 2016: Journal of Pharmaceutical Sciences
Laura J Waters, Dina S Shokry, Gareth M B Parkes, John C Mitchell
Human intestinal absorption (HIA) will dictate biopharmaceutical performance through its influence on absorption, distribution, metabolism, and elimination and can vary significantly depending upon the nature of the compound under consideration. In this study, an in vitro assay method is proposed for the prediction of HIA through the measurement of drug solubility in an aqueous phase containing micellar bile salt, namely sodium deoxycholate. A series of twenty compounds, displaying a range of physicochemical properties and known HIA values, were analyzed using UV spectroscopy to determine a solubilization ratio for each compound...
October 21, 2016: Journal of Pharmaceutical Sciences
Søren B van Witteloostuijn, Søren L Pedersen, Knud J Jensen
Peptides and proteins constitute a vast pool of excellent drug candidates. Evolution has equipped these molecules with superior drug-like properties such as high specificity and potency. However, native peptides and proteins suffer from an inadequate pharmacokinetic profile, and their outstanding pharmacological potential can only be realized if this issue is addressed during drug development. To overcome this challenge, a variety of half-life extension techniques relying on covalent chemical modification have been developed...
October 24, 2016: ChemMedChem
Laszlo Hajba, Eszter Csanky, Andras Guttman
Comprehensive carbohydrate analysis of glycoproteins from human biological samples and biotherapeutics are important from diagnostic and therapeutic points of view. This review summarizes the current state-of-the-art liquid phase separation techniques used in N-glycosylation analysis. The different liquid chromatographic techniques and capillary electrophoresis methods are critically discussed in detail. Miniaturization of these methods is also important to increase throughput and decrease analysis time. The sample preparation and labeling methods for asparagine linked oligosaccharides are also addressed...
November 2, 2016: Analytica Chimica Acta
Arathi Kizhedath, Simon Wilkinson, Jarka Glassey
Biopharmaceuticals, monoclonal antibody (mAb)-based therapeutics in particular, have positively impacted millions of lives. MAbs and related therapeutics are highly desirable from a biopharmaceutical perspective as they are highly target specific and well tolerated within the human system. Nevertheless, several mAbs have been discontinued or withdrawn based either on their inability to demonstrate efficacy and/or due to adverse effects. Approved monoclonal antibodies and derived therapeutics have been associated with adverse effects such as immunogenicity, cytokine release syndrome, progressive multifocal leukoencephalopathy, intravascular haemolysis, cardiac arrhythmias, abnormal liver function, gastrointestinal perforation, bronchospasm, intraocular inflammation, urticaria, nephritis, neuropathy, birth defects, fever and cough to name a few...
October 20, 2016: Archives of Toxicology
Monica R P Rao, Chaitanya Shirsath
Efavirenz is a non-nucleoside reverse transcriptase inhibitor which is chronically prescribed for HIV patients. However, it exhibits solubility-limited bioavailability. Aim of this work was to enhance the solubility and dissolution of the Biopharmaceutical Classification System (BCS) class II drug efavirenz, using beta-cyclodextrin-based nanosponges. Nanosponges have high drug loading capacity and are effective for solubility enhancement. Beta-cyclodextrin was crosslinked with carbonates in different ratios to prepare nanosponges...
October 18, 2016: AAPS PharmSciTech
Ting-Ting Zhao, Ling-Ling Zhu, Meng Chen, Quan Zhou
BACKGROUND: According to prescribing information for Myrtol standardized enteric-coated soft capsules, the medicine should be taken on an empty stomach. Some patients may experience stomach discomfort after oral administration in fasted state and would prefer to take the medicine after a meal. However, there is no literature addressing the effect of meal on absorption of this drug; therefore, it is desirable to explore the feasibility of taking the capsule after a meal from pharmacokinetic perspective...
2016: Patient Preference and Adherence
Irene Krämer, Matthias Blüher, Martin K Kuhlmann, Lutz Heinemann
Following the market authorization of the first insulin biosimilar in 2014, further approvals are to be expected due to patent expiry of several originator insulins. Knowledge of the manufacturing and the characteristics of these pharmaceutical products is important for their rationale and safe use by the physician, the pharmacist and the patient.Biosimilars are not generics, but similar or comparable, yet not identical versions of the originator biopharmaceutical. Marketing authorization in the EU is granted only after passing a stringent procedure...
October 2016: Deutsche Medizinische Wochenschrift
William F Weiss, John P Gabrielson, Wasfi Al-Azzam, Guodong Chen, Darryl L Davis, Tapan K Das, David B Hayes, Damian Houde, Satish K Singh
Characterization of the higher order structure (HOS) of protein-based biopharmaceutical products is an important aspect of their development. Opinions vary about how best to apply biophysical methods, in which contexts to use these methods, and how to use the resulting data to make technical decisions as drug candidates are commercialized [Gabrielson JP, Weiss WF IV. J Pharm Sci. 2015;104(4):1240-1245]. The aim of this commentary is to provide guidance for the development and implementation of a robust and comprehensive HOS characterization strategy...
October 12, 2016: Journal of Pharmaceutical Sciences
Marton Szigeti, Andras Guttman
N-glycan profiling of therapeutic glycoproteins is essential to ensure the activity and efficacy of these promising new-generation drugs. The N-linked glycan moieties of these entities highly affect circulation half-life, immunogenicity and receptor-binding activity as well as physicochemical and thermal stability properties. In addition, more than half of the biopharmaceuticals are glycoproteins representing multibillion dollar worldwide business, further emphasizing the importance of their analysis. In the biomedical field, on the other hand, revealing disease-related glycan structure alterations holds the promise of the discovery of new biomarkers for early diagnostics...
2017: Methods in Molecular Biology
Tongkai Chen, Chuwen Li, Ye Li, Yi Xiang, Simon Ming Yuen Lee, Ying Zheng
Schisantherin A (SA) is a promising anti-Parkinsonism Chinese herbal medicine but with poor water solubility and challenges to be delivered to the brain. We formulated SA as nanocrystals (SA-NC), aiming to improve its solubility, pharmacokinetic profile and thus provide a potential therapeutic agent for the treatment of Parkinson's disease (PD). The rod-shaped SA-NC had a particle size of ~160 nm with 33.3% drug loading, and the nanocrystals exhibited a fast dissolution rate in vitro. The intact drug nanocrystals could be internalized into Madin-Darby canine kidney (MDCK) cells, which were followed by rapid intracellular release, and most of the drug was transported to the basolateral side in its soluble form...
October 14, 2016: Molecular Pharmaceutics
Cinzia Pagano, Maria Cristina Tiralti, Luana Perioli
OBJECTIVES: Folic acid (FA) is an important source for the prevention of many diseases. However, its use is limited because the very low solubility (<10 mg/l particularly in the gastric environment) responsible for the incomplete adsorption of the administered dose. This study proposes a technological strategy to overcome this problem enhancing FA dissolution rate by means of a formulation able to make completely bioavailable the whole administered dose. METHODS: Folic acid was intercalated in the layered double hydroxides (LDHs) MgAl-LDH and ZnAl-LDH...
October 13, 2016: Journal of Pharmacy and Pharmacology
Nambin Yim, Chulhee Choi
Extracellular vesicles (EVs) are natural carriers of biomolecules that play central roles in cell-to-cell communications. Based on this, there have been many attempts to use EVs as therapeutic drug carriers. Various macromolecules, from chemical reagents to nucleic acids, were successfully loaded into EVs; however, loading of proteins with high molecular weight has been huddled with several problems. Purification of recombinant proteins is expensive and time consuming, and easily results in modification of proteins by physical or chemical forces...
October 13, 2016: BMB Reports
John Joseph Milne
Separation science continues to occupy the central position in the overall strategy for the downstream processing and purification of therapeutic protein products for human use. Increasing product titers from mammalian cell culture and new emerging classes of biopharmaceuticals has presented a challenge to the industry to identify ways of improving the robustness and economics of chromatography processes. In commercial manufacturing, there is always a need to increase the scale of the chromatography operations which are typically developed and optimized in small-scale laboratory experiments...
2017: Methods in Molecular Biology
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