Search results for "ODR"

Coupling of the antiviral agent zidovudine to polyaspartamide and in vitro drug release studies.

1998

A macromolecular prodrug of the known antiretroviral agent zidovudine and alpha, beta-poly(N-2-hydroxyethyl)-DL-aspartamide (PHEA) was synthesized. A succinic spacer was present between the polymer and the drug, and 1,1'-carbonyldiimidazole was used as the coupling agent. In vitro drug release studies at pH 1.1, 5.5 and 7.4 indicated that limited amounts of intact drug were released from the conjugate. At pH 1.1 and 7.4 succinylzidovudine was released, and this was hydrolysed to give free zidovudine. In the presence of alpha-chymotrypsin, zidovudine was released preferentially in comparison with the succinyl derivative. The amounts of released zidovudine and succinylzidovudine were greater …

Dendrimers as Non-Viral Vectors in Gene-Directed Enzyme Prodrug Therapy.

2021

Gene-directed enzyme prodrug therapy (GDEPT) has been intensively studied as a promising new strategy of prodrug delivery, with its main advantages being represented by an enhanced efficacy and a reduced off-target toxicity of the active drug. In recent years, numerous therapeutic systems based on GDEPT strategy have entered clinical trials. In order to deliver the desired gene at a specific site of action, this therapeutic approach uses vectors divided in two major categories, viral vectors and non-viral vectors, with the latter being represented by chemical delivery agents. There is considerable interest in the development of non-viral vectors due to their decreased immunogenicity, higher…

Biowaiver Monographs for Immediate-Release Solid Oral Dosage Forms: Enalapril

2018

Literature data relevant to the decision to allow a waiver of in vivo bioequivalence testing for the marketing authorization of immediate-release, solid oral dosage forms containing enalapril maleate are reviewed. Enalapril, a prodrug, is hydrolyzed by carboxylesterases to the active angiotensin-converting enzyme inhibitor enalaprilat. Enalapril as the maleate salt is shown to be highly soluble, but only 60%-70% of an orally administered dose of enalapril is absorbed from the gastrointestinal tract into the enterocytes. Consequently, enalapril maleate is a Biopharmaceutics Classification System class III substance. Because in situ conversion of the maleate salt to the sodium salt is sometim…

Potential transbuccal delivery of l-DOPA methylester prodrug: stability in the environment of the oral cavity and ability to cross the mucosal tissue

2016

Levodopa (l-DOPA) is the most effective pharmacologic agent in Parkinson's disease and remains the "gold standard". Nevertheless, in long-term treatments, dyskinesias and motor complications can emerge. In this work, the combined use of l-DOPA methylester hydrochloride prodrug (LDME) with transbuccal drug delivery was supposed as a good alternative method to optimize the bioavailability of l-DOPA, to maintain constant plasma levels and to decrease the drug unwanted effects. The effects of environmental pH on buccal delivery of LDME were evaluated ex vivo. The increase of pH value from 5.8 to 6.2 implies an improvement of drug permeation. Since the pH increase causes the raising of hydrolyti…

Triplet stabilization for enhanced drug photorelease from sunscreen-based photocages

2021

[EN] Recently, sunscreen-based drug photocages have been introduced to provide UV protection to photoactive drugs, thus increasing their photosafety. Here, combined experimental and theoretical studies performed on a photocage based on the commercial UVA filter avobenzone (AB) and on the photosensitizing non-steroidal anti-inflammatory drug ketoprofen (KP) are presented unveiling the photophysical processes responsible for the light-triggered release. Particular attention is paid to solvent stabilization of the drug and UV filter excited states, respectively, which leads to a switching between the triplet excited state energies of the AB and KP units. Most notably, we show that the stabiliz…

Frontiers of metal-coordinating drug design

2020

INTRODUCTION: The occurrence of metal ions in biomolecules is required to exert vital cellular functions. Metal-containing biomolecules can be modulated by small-molecule inhibitors targeting their metal-moiety. As well, the discovery of cisplatin ushered the rational discovery of metal-containing-drugs. The use of both drug types exploiting metal–ligand interactions is well established to treat distinct pathologies. Therefore, characterizing and leveraging metal-coordinating drugs is a pivotal, yet challenging, part of medicinal chemistry. AREA COVERED: Atomic-level simulations are increasingly employed to overcome the challenges met by traditional drug-discovery approaches and to compleme…

Calixarene: A Versatile Material for Drug Design and Applications

2016

The therapy of various diseases by the drugs entrapped in calixarene derivatives is gaining attraction of researchers nowadays. Calixarenes are macrocyclic nano-baskets which belong to cavitands class of host-guest chemistry. They are the marvelous hosts with distinct hydrophobic three dimensional cavities to entrap and encapsulate biologically active guest drugs. Calixarene and its derivatives develop inclusion complexes with various types of drugs and vitamins for their sustained/targeted release. Calixarene and its derivatives are used as carriers for anti-cancer, anti-convulsant, anti-hypertensive, anthelmentic, anti-inflammatory, antimicrobial and antipsychotic drugs. They are the impo…

Historia verdadera, y famosa del Cid Campeador, Don Rodrigo Diaz de Vivar. Sacada de los mas celebres, y gravisimos Autores, y expurgada de varias fa…

Text a dues col Reclams Grav. xil. enmarcat a la port. avant del tít., representant al Cid

Ekosistēmu pakalpojumu apzināšana Rīgas pilsētā vides kvalitātes novērtēšanai un uzraudzībai apkaimju līmenī

2021

Maģistra darba “Ekosistēmu pakalpojumu apzināšana Rīgas pilsētvides monitoringam un uzraudzībai apkaimju līmenī” mērķis ir izstrādāt ekosistēmu pakalpojumu apzināšanas un monitoringa modeli, lai efektīvāk plānotu pilsētvidi un ar to saistītus problēmu risinājumus apkaimju līmenī. Pētījuma ietvaros definēti trīs apgādes, septiņi vidi regulējoši un seši kultūras ekosistēmu pakalpojumi, kā arī 41 to raksturojošais indikators. Ekosistēmu pakalpojuma nodrošinājuma apzināšanas metodes matrica ļauj to pēc nepieciešamības pielāgot un piemērot, mainot raksturojošo indikatoru algoritmus un aprēķinus. Pētījuma mērķis ir izstrādāt ekosistēmu pakalpojumu nodrošinājuma apzināšanas metodoloģisku ietvaru, …

Inverting Multiple Residual Stress Components from Multiple Cuts with the Contour Method

2007

An extension of the contour method is presented which allows the measurement of multiple stress components by making multiple cuts. In the contour method, a body is carefully cut in two using wire electric discharge machining (EDM). The contours, or shapes, of the cut surfaces are then measured and used to calculate the original residual stress normal to the cut plane using a simple finite element calculation. In the extension presented here, the two pieces from the original body can be cut again in a transverse direction, and the contours of the new cut surfaces are measured. The stresses calculated on the planes of these second cuts have been affected by the first cut. Then a simple inver…