Pharmaceutical Research

http://link.springer.com/journal/11095

List of Papers (Total 349)

Microneedles: A New Frontier in Nanomedicine Delivery

This review aims to concisely chart the development of two individual research fields, namely nanomedicines, with specific emphasis on nanoparticles (NP) and microparticles (MP), and microneedle (MN) technologies, which have, in the recent past, been exploited in combinatorial approaches for the efficient delivery of a variety of medicinal agents across the skin. This is an...

Lomustine Nanoparticles Enable Both Bone Marrow Sparing and High Brain Drug Levels – A Strategy for Brain Cancer Treatments

Purpose The blood brain barrier compromises glioblastoma chemotherapy. However high blood concentrations of lipophilic, alkylating drugs result in brain uptake, but cause myelosuppression. We hypothesised that nanoparticles could achieve therapeutic brain concentrations without dose-limiting myelosuppression. Methods Mice were dosed with either intravenous lomustine Molecular...

Translational Modeling in Schizophrenia: Predicting Human Dopamine D2 Receptor Occupancy

Objectives To assess the ability of a previously developed hybrid physiology-based pharmacokinetic-pharmacodynamic (PBPKPD) model in rats to predict the dopamine D2 receptor occupancy (D2RO) in human striatum following administration of antipsychotic drugs. Methods A hybrid PBPKPD model, previously developed using information on plasma concentrations, brain exposure and D2RO in...

Incentives for Starting Small Companies Focused on Rare and Neglected Diseases

Starting biotech or pharmaceutical companies is traditionally thought to be based around a scientist, their technology platform or a clinical candidate spun out from another company. Between us we have taken a different approach and formed two small early stage companies after initially leveraging the perspective of a parent with a child with a life-threatening rare disease...

Structure-Based Prediction of Anti-infective Drug Concentrations in the Human Lung Epithelial Lining Fluid

Purpose Obtaining pharmacologically relevant exposure levels of antibiotics in the epithelial lining fluid (ELF) is of critical importance to ensure optimal treatment of lung infections. Our objectives were to develop a model for the prediction of the ELF-plasma concentration ratio (EPR) of antibiotics based on their chemical structure descriptors (CSDs). Methods EPR data was...

Controlled Release from Zein Matrices: Interplay of Drug Hydrophobicity and pH

Purpose In earlier studies, the corn protein zein is found to be suitable as a sustained release agent, yet the range of drugs for which zein has been studied remains small. Here, zein is used as a sole excipient for drugs differing in hydrophobicity and isoelectric point: indomethacin, paracetamol and ranitidine. Methods Caplets were prepared by hot-melt extrusion (HME) and...

Multivariate Analysis of Effects of Asthmatic Patient Respiratory Profiles on the In Vitro Performance of a Reservoir Multidose and a Capsule-Based Dry Powder Inhaler

Purpose The aim of this work was to evaluate the effect of two different dry powder inhalers, of the NGI induction port and Alberta throat and of the actual inspiratory profiles of asthmatic patients on in-vitro drug inhalation performances. Methods The two devices considered were a reservoir multidose and a capsule-based inhaler. The formulation used to test the inhalers was a...

Model-Based Optimisation of Deferoxamine Chelation Therapy

Purpose Here we show how a model-based approach may be used to provide further insight into the role of clinical and demographic covariates on the progression of iron overload. The therapeutic effect of deferoxamine is used to illustrate the application of disease modelling as a means to characterising treatment response in individual patients. Methods Serum ferritin, demographic...

Assessment of Interspecies Differences in Drug-Induced QTc Interval Prolongation in Cynomolgus Monkeys, Dogs and Humans

Background and Purpose The selection of the most suitable animal species and subsequent translation of the concentration-effect relationship to humans are critical steps for accurate assessment of the pro-arrhythmic risk of candidate molecules. The objective of this investigation was to assess quantitatively the differences in the QTc prolonging effects of moxifloxacin between...

Pharmacokinetics, Tissue Distribution and Therapeutic Effect of Cationic Thermosensitive Liposomal Doxorubicin Upon Mild Hyperthermia

Purpose To evaluate pharmacokinetic profile, biodistribution and therapeutic effect of cationic thermosensitive liposomes (CTSL) encapsulating doxorubicin (Dox) upon mild hyperthermia (HT). Methods Non-targeted thermosensitive liposomes (TSL) and CTSL were developed, loaded with Dox and characterized. Blood kinetics and biodistribution of Dox-TSL and Dox-CTSL were followed in...

Physiologically-Based Pharmacokinetic and Pharmacodynamic Modeling for the Inhibition of Acetylcholinesterase by Acotiamide, A Novel Gastroprokinetic Agent for the Treatment of Functional Dyspepsia, in Rat Stomach

Purpose Acotiamide, a gastroprokinetic agent used to treat functional dyspepsia, is transported to at least two compartments in rat stomach. However, the role of these stomach compartments in pharmacokinetics and pharmacodynamics of acotiamide remains unclear. Thus, the purpose of this study was to elucidate the relationship of the blood and stomach concentration of acotiamide...

Electrospun Zein/PCL Fibrous Matrices Release Tetracycline in a Controlled Manner, Killing Staphylococcus aureus Both in Biofilms and Ex Vivo on Pig Skin, and are Compatible with Human Skin Cells

Purpose To investigate the destruction of clinically-relevant bacteria within biofilms via the sustained release of the antibiotic tetracycline from zein-based electrospun polymeric fibrous matrices and to demonstrate the compatibility of such wound dressing matrices with human skin cells. Methods Zein/PCL triple layered fibrous dressings with entrapped tetracycline were...

The Effect of Excipients on the Permeability of BCS Class III Compounds and Implications for Biowaivers

Purpose Currently, the FDA allows biowaivers for Class I (high solubility and high permeability) and Class III (high solubility and low permeability) compounds of the Biopharmaceutics Classification System (BCS). Scientific evidence should be provided to support biowaivers for BCS Class I and Class III (high solubility and low permeability) compounds. Methods Data on the effects...

Self-Interaction Chromatography of mAbs: Accurate Measurement of Dead Volumes

Purpose Measurement of the second virial coefficient B22 for proteins using self-interaction chromatography (SIC) is becoming an increasingly important technique for studying their solution behaviour. In common with all physicochemical chromatographic methods, measuring the dead volume of the SIC packed column is crucial for accurate retention data; this paper examines best...

In Vitro Assessment of Uptake and Lysosomal Sequestration of Respiratory Drugs in Alveolar Macrophage Cell Line NR8383

Purpose To assess accumulation and lysosomal sequestration of 9 drugs used in respiratory indications (plus imipramine as positive control) in the alveolar macrophage (AM) cell line NR8383. Methods For all drugs, uptake at 5 μM was investigated at 37 and 4°C to delineate active uptake and passive diffusion processes. Accumulation of basic clarithromycin, formoterol and imipramine...

The Pharmacokinetics of the CYP3A Substrate Midazolam in Morbidly Obese Patients Before and One Year After Bariatric Surgery

Purpose Bariatric surgery is nowadays commonly applied as treatment for morbid obesity (BMI > 40 kg/m2). As information about the effects of this procedure on a drug’s pharmacokinetics is limited, we aimed to evaluate the pharmacokinetics of CYP3A probe substrate midazolam after oral and intravenous administration in a cohort of morbidly obese patients that was studied before and...

Enhanced Specificity and Drug Delivery in Tumors by cRGD - Anchoring Thermosensitive Liposomes

Purpose To develop RGD-targeted thermosensitive liposomes with increased tumor retention, improving drug release efficiency upon mild hyperthermia (HT) in both tumor and angiogenic endothelial cells. Methods Standard termosensitive liposomes (TSL) and TSL containing a cyclic Arg-Gly-Asp (cRGD) pentapeptide with the sequence Arg-Cys-D-Phe-Asp-Gly (RGDf[N-Met]C) were synthetized...

Multilayered Thin Films from Boronic Acid-Functional Poly(amido amine)s As Drug-Releasing Surfaces

Purpose To evaluate the potential of poly(amido amine)-based multilayered thin films in surface mediated drug release. Methods Multilayered thin films were prepared from copolymers of phenylboronic acid-functional poly(amido amine)s and chondroitin sulfate (ChS) in the presence of Alizarin Red S (ARS) as a reporter molecule. Multilayer buildup and ARS incorporation were evaluated...

Cationic Liposome- Multi-Walled Carbon Nanotubes Hybrids for Dual siPLK1 and Doxorubicin Delivery In Vitro

Purpose To formulate f-MWNTs-cationic liposome hybrids for the simultaneous delivery of siPLK1 and doxorubicin to cancer cells. Method f-MWNTs-cationic liposome hybrids were prepared by the thin film hydration method where the lipid film was hydrated with 100 μg/ml or 1 mg/ml of ox-MWNTs-NH3 + or MWNTs-NH3 + in 5% dextrose. siRNA complexation and protection ability was determined...