Identification of the anti-fungal drug fenticonazole nitrate as a novel PPARγ-modulating ligand with good therapeutic index: Structure-based screening and biological validation

2021 ◽  
Vol 173 ◽  
pp. 105860
Author(s):  
Lei Ma ◽  
Yuling Lian ◽  
Junyuan Tang ◽  
Fangyuan Chen ◽  
Hui Gao ◽  
...  
Keyword(s):  
Therapeutic Index ◽  
Index Structure ◽  
Biological Validation ◽  
Anti Fungal

Thrombolytic Treatment with Tissue-type Plasminogen Activator (t-PA) Containing Liposomes in Rabbits: a Comparison with Free t-PA

1995 ◽  
Vol 73 (03) ◽  
pp. 488-494 ◽  
Author(s):  
J L M Heeremans ◽  
R Prevost ◽  
M E A Bekkers ◽  
P Los ◽  
J J Emeis ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Therapeutic Index ◽  
Tissue Type ◽  
Jugular Vein Thrombosis ◽  
Thrombolytic Activity ◽  
Tissue Type Plasminogen Activator ◽  
Liposome Encapsulation ◽  
Thrombosis Model ◽  
Lysis Activity ◽  
Type Plasminogen Activator

SummaryIn this study, we aimed at improving the therapeutic index of tissue- type Plasminogen Activator (t-PA) as thrombolytic agent in the treatment of myocardial infarction. Liposome-encapsulated t-PA was tested in a rabbit jugular vein thrombosis model: administration of free t-PA (t-PA) as a bolus injection in the ear vein was compared to a similar administration of liposomal t-PA (t-PA-lip), liposomal t-PA in plasminogen-coated liposomes (Plg-t-PA-lip), a mixture of free t-PA and empty liposomes (t-PA+empty lip) and a saline-blank (blank) in terms of thrombolytic activity and side effects.Liposomal t-PA (t-PA-lip/Plg-t-PA-lip) showed a significantly better thrombolysis efficiency than equimolar doses of free t-PA (t-PA/ t-PA+ empty lip): about 0.24 mg/kg of liposomal t-PA practically equalled the lysis-activity of a dose of free t-PA of 1.0 mg/kg (t-PAlmg/kg). On the other hand, liposome encapsulation did not affect the systemic activation of alpha2-antiplasmin and plasminogen by t-PA.We conclude that for this model an improvement in thrombolytic efficacy of t-PA is achieved by liposome encapsulation of t-PA. As t-PA-lip and Plg-t-PA-lip -treatment induced similar results, targeting of liposomal t-PA by coupled glu-Plg remains a topic to be optimized in future studies.

In vitro anti-fungal activity of a plant-based ear gel and its essential oils

Planta Medica ◽  
2006 ◽  
Vol 72 (11) ◽  
Author(s):  
JK Ketzis ◽  
N Nolard ◽  
NS Ryder
Keyword(s):  
Essential Oils ◽  
Fungal Activity ◽  
Anti Fungal

Artemisinin (ART) Drug Delivery Using Mixed Non-ionic Surfactants and Evaluation of Their Efficiency in Different Cancer Cell Lines

2017 ◽  
Vol 4 (4) ◽  
Author(s):  
Elnaz Asgharkhani ◽  
Aazam Najmafshar ◽  
Mohsen Chiani
Keyword(s):  
Zeta Potential ◽  
Cell Line ◽  
Mtt Assay ◽  
Therapeutic Index ◽  
Stability Study ◽  
Polydispersity Index ◽  
Ionic Surfactants ◽  
Cytotoxicity Test ◽  
Molar Ratios ◽  
Chemotherapy Agent

This study aims to investigate the effects of different non-ionic surfactants on physicochemical properties of ART niosomes. ART is a natural compound that is used as an antimalarial and chemotherapy agent in medicine. ART has low bioavailability, stability and solubility. In order to solve these problems and enhancing the efficiency of the drug, nanotechnology was used. In the present study, several niosomal formulations of ART prepared using different molar ratios of Span 60 : Tween 60 : PEG-600: ART in PBS. These three formulations were FI (1:1:0.5:0.5), FII (2:1:0.5:0.5) and FIII (1:2:0.5:0.5), respectively. The encapsulation efficiency was measured by HPLC and the drug release was evaluated by dialysis method. The cytotoxicity test was determined by MTT assay. The size, zeta potential and polydispersity index of the vesicles was measured by Zeta Sizer. Stability study was performed within two months. The MTT assay results showed that cytotoxicity effect of these formulations on MCF-7 cell line is better than C6 cell line and the FIII had the best results for both of them. The entrapment efficiencies of the formulations I, II and III were obtained 82.2±1.88%, 75.5±0.92% and 95.5±1.23%, respectively. The results of size, zeta potential and polydispersity index indicated that the size of the vesicles is below 200 nm, their surface charge is about -35 mV and they were monodisperse. Stability and release study indicated that the formulation III has the best stability and release pattern. Therefore, the use of PEGylated niosomal ART can effectively improve its therapeutic index, stability and solubility.

A Plug-and-Play Approach for the De Novo Generation of Dually Functionalised Bispecifics

2019 ◽  
Author(s):  
Antoine Maruani ◽  
Peter A. Szijj ◽  
Calise Bahou ◽  
João C. F. Nogueira ◽  
Stephen Caddick ◽  
...  
Keyword(s):  
De Novo ◽  
Therapeutic Index ◽  
Antibody Fragments ◽  
Bispecific Antibodies ◽  
Full Potential ◽  
Mechanisms Of Resistance ◽  
Large Excess ◽  
Chemical Methods ◽  
New Class ◽  
Novel Approach

<p>Diseases are multifactorial, with redundancies and synergies between various pathways. However, most of the antibody-based therapeutics in clinical trials and on the market interact with only one target thus limiting their efficacy. The targeting of multiple epitopes could improve the therapeutic index of treatment and counteract mechanisms of resistance. To this effect, a new class of therapeutics emerged: bispecific antibodies.</p><p>Bispecific formation using chemical methods is rare and low yielding and/or requires a large excess of one of the two proteins to avoid homodimerisation. In order for chemically prepared bispecifics to deliver their full potential, high-yielding, modular and reliable cross-linking technologies are required. Herein, we describe a novel approach not only for the rapid and high-yielding chemical generation of bispecific antibodies from native antibody fragments, but also for the site-specific dual functionalisation of the resulting bioconjugates. Based on orthogonal clickable functional groups, this strategy enables the assembly of functionalised bispecifics with controlled loading in a modular and convergent manner.</p>

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