Chemoprophylaxis is currently the best available prevention from malaria, but its efficacy is compromised by non-adherence to medication. Here we develop a long-acting injectable formulation of atovaquone solid drug nanoparticles that confers long-lived prophylaxis againstPlasmodium bergheiANKA malaria in C57BL/6 mice. Protection is obtained at plasma concentrations above 200 ng ml-1and is causal, attributable to drug activity against liver stage parasites. Parasites that appear after subtherapeutic doses remain atovaquone-sensitive. Pharmacokinetic–pharmacodynamic analysis indicates protection can translate to humans at clinically achievable and safe drug concentrations, potentially offering protection for at least 1 month after a single administration. These findings support the use of long-acting injectable formulations as a new approach for malaria prophylaxis in travellers and for malaria control in the field.
1 December 2014 in Sensing and Bio-Sensing Research
The standard method for the detection of botulinum neurotoxin is currently the mouse bioassay which is considered to be the most reliable method for the detection of the active form of this toxin. Despite this it is a time-consuming and expensive assay to run and as such many alternative assays have recently been proposed. Herein we report the development of two electrochemical assays for the detection of active botulinum neurotoxin in a pharmaceutical sample. Gold electrodes were modified with self-assembled monolayers of the SNARE protein SNAP-25 which is selectively cleaved by active botulinum neurotoxin A. Cyclic voltammetry and electrochemical impedance spectroscopy were performed on the modified working electrodes to observe changes to the layer on addition of the toxin. Both methods were able to distinguish the difference between the presence of the active toxin and a placebo containing the excipients of the pharmaceutical product. The electrochemical impedance spectroscopy assay also allowed for detection of the active toxin at concentrations as low as 25fg/ml, with results being obtained in under an hour outperforming the mouse bioassay
1 May 2019 in European Journal of Pharmaceutics and Biopharmaceutics
Water soluble gold nanoparticles are coated with peptides bearing a dithiol surface active group for studies of lanthanide binding; characteristic red luminescence is observed upon europium binding to the nanoparticles.
Botulinum neurotoxin is one of the deadliest biological toxins known to mankind and is able to cause the debilitating disease botulism. The rapid detection of the different serotypes of botulinum neurotoxin is essential for both diagnosis of botulism and identifying the presence of toxin in potential cases of terrorism and food contamination. The modes of action of botulinum neurotoxins are well-established in literature and differ for each serotype. The toxins are known to specifically cleave portions of the SNARE proteins SNAP-25 or VAMP; an interaction that can be monitored by electrochemical impedance spectroscopy. This study presents a SNAP-25 and a VAMP biosensors for detecting the activity of five botulinum neurotoxin serotypes (A–E) using electrochemical impedance spectroscopy. The biosensors are able to detect concentrations of toxins as low as 25 fg/mL, in a short time-frame compared with the current standard methods of detection. Both biosensors show greater specificity for their compatible serotypes compared with incompatible serotypes and denatured toxins.