4 research outputs found
Metal nanoparticles: understanding the mechanisms behind antibacterial activity
As the field of nanomedicine emerges, there is a lag in research surrounding the topic of nanoparticle (NP) toxicity, particularly concerned with mechanisms of action. The continuous emergence of bacterial resistance has challenged the research community to develop novel antibiotic agents. Metal NPs are among the most promising of these because show strong antibacterial activity. This review summarizes and discusses proposed mechanisms of antibacterial action of different metal NPs. These mechanisms of bacterial killing include the production of reactive oxygen species, cation release, biomolecule damages, ATP depletion, and membrane interaction. Finally, a comprehensive analysis of the effects of NPs on the regulation of genes and proteins (transcriptomic and proteomic) profiles is discussed.Medicine, Faculty ofPharmaceutical Sciences, Faculty ofInfectious Diseases, Division ofMedicine, Department ofReviewedFacult
Refinement and validation of infrared thermal imaging (IRT): a non-invasive technique to measure disease activity in a mouse model of rheumatoid arthritis
Background:
The discovery and development of new medicines requires high-throughput screening of possible therapeutics in a specific model of the disease. Infrared thermal imaging (IRT) is a modern assessment method with extensive clinical and preclinical applications. Employing IRT in longitudinal preclinical setting to monitor arthritis onset, disease activity and therapeutic efficacies requires a standardized framework to provide reproducible quantitative data as a precondition for clinical studies.
Methods:
Here, we established the accuracy and reliability of an inexpensive smartphone connected infrared (IR) camera against known temperature objects as well as certified blackbody calibration equipment. An easy to use protocol incorporating contactless image acquisition and computer-assisted data analysis was developed to detect disease-related temperature changes in a collagen-induced arthritis (CIA) mouse model and validated by comparison with two conventional methods, clinical arthritis scoring and paw thickness measurement. We implemented IRT to demonstrate the beneficial therapeutic effect of nanoparticle drug delivery versus free methotrexate (MTX) in vivo.
Results:
The calibrations revealed high accuracy and reliability of the IR camera for detecting temperature changes in the rheumatoid arthritis animal model. Significant positive correlation was found between temperature changes and paw thickness measurements as the disease progressed. IRT was found to be superior over the conventional techniques specially at early arthritis onset, when it is difficult to observe subclinical signs and measure structural changes.
Conclusion:
IRT proved to be a valid and unbiased method to detect temperature changes and quantify the degree of inflammation in a rapid and reproducible manner in longitudinal preclinical drug efficacy studies.Pharmaceutical Sciences, Faculty ofScience, Faculty ofNon UBCPhysics and Astronomy, Department ofReviewedFacult
Microfluidic-Based Synthesis of Magnetic Nanoparticles Coupled with Miniaturized NMR for Online Relaxation Studies
Using compact desktop
NMR systems for rapid characterization of
relaxation properties directly after synthesis can expedite the development
of functional magnetic nanoparticles. Therefore, an automated system
that combines a miniaturized NMR relaxometer and a flow-based microreactor
for online synthesis and characterization of magnetic iron oxide nanoparticles
is constructed and tested. NMR relaxation properties are quantified
online with a 0.5 T permanent magnet for measurement of transverse
(<i>T</i><sub>2</sub>) and longitudinal (<i>T</i><sub>1</sub>) relaxation times. Nanoparticles with a primary particle
size of about 25 nm are prepared by coprecipitation in a tape-based
microreactor that utilizes 3D hydrodynamic flow focusing to avoid
channel clogging. Cluster sizes are expeditiously optimized for maximum
transverse relaxivity of 115.5 mM s<sup>–1</sup>. The compact
process control system is an efficient tool that speeds up synthesis
optimization and product characterization of magnetic nanoparticles
for nanomedical, theranostic, and NMR-based biosensing applications
A Novel Leu-Enkephalin Prodrug Produces Pain-Relieving and Antidepressant Effects
Persistent
pain is a significant healthcare problem with limited
treatment options. The high incidence of comorbid chronic pain and
depression significantly reduces life quality and complicates the
treatment of both conditions. Antidepressants are less effective for
pain and depression than for depression alone and they induce severe
side effects. Opioids are highly efficacious analgesics, but rapid
development of tolerance, dependence, and debilitating side effects
limit their efficacy and safe use. Leucine-enkephalin (Leu-ENK), the
endogenous delta opioid receptor agonist, controls pain and mood and
produces potent analgesia with reduced adverse effects compared to
conventional opioids. High proteolytic instability, however, makes
Leu-ENK ineffective after systemic administration and limits its clinical
usefulness. KK-103, a Leu-ENK prodrug, was developed to overcome these
limitations of Leu-ENK via markedly increased plasma stability in
mice. We showed rapid and substantially increased systemic adsorption
and blood plasma exposure of KK-103 compared to Leu-ENK. We also observed
brain uptake of radiolabeled KK-103 after systemic administration,
indicating a central effect of KK-103. We then established KK-103’s
prolonged antinociceptive efficacy in the ramped hot plate and formalin
test. In both models, KK-103 produced a comparable dose to the maximum
antinociceptive-effect relationship. The pain-alleviating effect of
KK-103 primarily resulted from activating the delta opioid receptor
after the likely conversion of KK-103 to Leu-ENK in vivo. Finally,
KK-103 produced an antidepressant-like activity comparable to the
antidepressant desipramine, but with minimal gastrointestinal inhibition
and no incidence of sedation