Search results for "Note"
showing 10 items of 10709 documents
Regional Intestinal Drug Permeability and Effects of Permeation Enhancers in Rat
2020
Sufficient colonic absorption is necessary for all systemically acting drugs in dosage forms that release the drug in the large intestine. Preclinically, colonic absorption is often investigated using the rat single-pass intestinal perfusion model. This model can determine intestinal permeability based on luminal drug disappearance, as well as the effect of permeation enhancers on drug permeability. However, it is uncertain how accurate the rat single-pass intestinal perfusion model predicts regional intestinal permeability and absorption in human. There is also a shortage of systematic in vivo investigations of the direct effect of permeation enhancers in the small and large intestine. In …
An ex-vivo model for transsynovial drug permeation of intraarticular injectables in naive and arthritic synovium
2021
Abstract Estimation of joint residence time of a drug is a key requirement for rational development of intraarticular therapeutics. There is a great need for a predictive model to reduce the high number of animal experiments in early stage development. Here, a Franz-cell based porcine ex-vivo permeation model is proposed, and transsynovial permeation of fluorescently-labeled dextrans in the range of potential drug candidates (10–150 kDa), as well as a small molecule (fluorescein sodium) and charged dextran derivates, have been determined. In addition, a lipopolysaccharide (LPS) -induced synovitis model was assessed for inflammatory biomarker levels and its effect on permeation of the solute…
PLGA nanoparticles are effective to control the colonic release and absorption on ibuprofen.
2018
The oral controlled release (CR) formulations have become more important in recent years. Among them, the polymeric nanoparticles have been thoroughly studied during the last decades, consequently they are extensively employed for a broad range of applications and drugs. The objective of this research was to develop polymeric nanoparticles (NPs) of ibuprofen with poly(lactic-co-glycolic) acid (PLGA) as polymer, and to test their applicability for oral CR formulations development. Different proportions of drug/polymer were employed to develop the ibuprofen NPs and their in vitro release profiles were analysed. The in situ segmental permeability of ibuprofen was tested in Wistar rat and demon…
Development of an ion-pair to improve the colon permeability of a low permeability drug: Atenolol.
2016
Abstract To ensure the optimal performance of oral controlled release formulations, drug colon permeability is one of the critical parameters. Consequently developing this kind of formulations for low permeability molecules requires strategies to increase their ability to cross the colonic membrane. The objective of this work is to show if an ion-pair formation can improve the colon permeability of atenolol as a low permeability drug model. Two counter ions have been tested: brilliant blue and bromophenol blue. The Distribution coefficients at pH 7.00 (DpH7) of atenolol, atenolol + brilliant blue and atenolol + bromophenol blue were experimentally determined in n-octanol. Moreover, the colo…
From In Silico to Experimental Validation: Tailoring Peptide Substrates for a Serine Protease.
2020
Smart nanocarriers for the transport of drugs to tumor cells are nowadays of great interest for treating cancer. The use of enzymatic stimuli to cleave peptide-based drug nanocapsules for the selective release of nanocapsule cargo in close proximity to tumor cells opens new possibilities in cancer research. In the present work, we demonstrate a methodology for finding and optimizing cleavable substrate sequences by the type II transmembrane serine protease hepsin, which is highly overexpressed in prostate cancer. The design and screening of combinatorial libraries in silico against the binding cavity of hepsin allow the identification of a panel of promising substrates with high-calculated …
Design and development of hyaluronan-functionalized polybenzofulvene nanoparticles as CD44 receptor mediated drug delivery system
2017
A tri-component polymer brush (TCPB), composed of a polybenzofulvene copolymer bearing low molecular weight hyaluronic acid (HA) on the surface of its cylindrical brush-like backbone and oligo-PEG fractions, was employed in the preparation of 350Â nm nanostructured drug delivery systems capable of delivering the anticancer drug doxorubicin. The obtained drug delivery systems were characterized on the basis of drug loading and release, dimensions and zeta potential, morphology and in vitro cell activity, and uptake on three different human cell lines, namely the bronchial epithelial 16HBE, the breast adenocarcinoma MCF-7, and the colon cancer HCT116 cells. Finally, the ability of doxorubicin…
Dense drug-eluting biodegradable Fe-Ag nanocomposites
2021
Abstract Biodegradable metals in orthopedics are aimed to eliminate secondary the surgical intervention for implant removal, and thus improve patient compliance, reduce surgery costs and the risk of infections. In addition, biodegradable implants could be loaded with different drugs to prevent the growth of pathogens and the development of bone infections, kill remaining cancer cells after tumor resection or stimulate bone regeneration. However, drugs undergo thermal decomposition under the conditions of conventional metal fabrication processes. In this work, we describe the fabrication of a dense drug-eluting biodegradable Fe-Ag nanocomposite containing 10 vol% of Ag and loaded with the an…
Antibacterial drug release from a biphasic gel system: Mathematical modelling
2019
Bacterial infections represent an important drawback in the orthopaedic field, as they can develop either immediately after surgery procedures or after some years. Specifically, in case of implants, they are alleged to be troublesome as their elimination often compels a surgical removal of the infected implant. A possible solution strategy could involve a local coating of the implant by an antibacterial system, which requires to be easily applicable, biocompatible and able to provide the desired release kinetics for the selected antibacterial drug. Thus, this work focusses on a biphasic system made up by a thermo-reversible gel matrix (Poloxamer 407/water system) hosting a dispersed phase (…
Nanomedicine: A Diagnostic and Therapeutic Approach to COVID-19
2021
The SARS-CoV-2 virus is causing devastating morbidity and mortality worldwide. Nanomedicine approaches have a high potential to enhance conventional diagnostics, drugs and vaccines. In fact, lipid nanoparticle/mRNA vaccines are already widely used to protect from COVID-19. In this review, we present an overview of the taxonomy, structure, variants of concern, epidemiology, pathophysiology and detection methods of SARS-CoV-2. The efforts of repurposing, tailoring, and adapting pre-existing medications to battle COVID-19 and the state of vaccine developments are presented. Next, we discuss the broad concepts and limitations of how nanomedicine could address the COVID-19 threat. Nanomaterials …
Utilizing inherent fluorescence of therapeutics to analyze real-time uptake and multi-parametric effector kinetics.
2011
Abstract The precise detection of pharmaceutical drug uptake and knowledge of a drug’s efficacy at the single-cell level is crucial for understanding a compound’s performance. Many pharmaceutical drugs, like the model substances Doxorubicin, Mitoxantrone or Irinotecan, have a distinctive natural fluorescence that can be readily exploited for research purposes. Utilizing this respective natural fluorescence, we propose a method analyzing simultaneously in real-time the efficiency, effects and the associated kinetics of compound-uptake and efflux in mammalian cells by flow cytometry. We show that real-time flow cytometric quantification of compound-uptake is reliably measured and that analyzi…