Mechanism Using Near-Infrared Light Could Lead to More Efficient Drug Delivery From Polymeric Particles
Researchers trigger payload release from polymeric particles using near-infrared light
A recently published study by researchers at the University of California, San Diego (CA, USA) has demonstrated the feasibility of using near-infrared (NIR) light to trigger the release of payloads from polymeric capsules. The findings suggest that the mechanism could be used for spatiotemporal and remote control over the release of small molecules, which would have a significant impact on biological research.
Although there are existing mechanisms for NIR-triggered release, these have not been widely applied due to the requirements for custom synthesis of designer polymers, high-powered lasers to drive inefficient two-photon processes and/or coencapsulation of bulky inorganic particles. The team therefore focused on developing a simpler mechanism and formulated a strategy that involves exploiting the behavior of water. They found that targeting the vibrational absorption band of water at 980 nm induced the release of payloads encapsulated in particles made from polymers with no inherent light sensitivity. The researchers hypothesized that this occurred as a result of water diffusion into the polymer particles and conductive heat transfer from the excited water droplets to the polymer matrix upon exposure to the NIR light, inducing a phase change of the polymer particles and increasing their diffusivity.
The controlled release of both hydrophilic and hydrophobic small molecules in aqueous environments and living cells is described in the study. The researchers also demonstrated how the rate of release could be controlled by changing the average NIR photon energy administered, and how multiple release doses could be achieved by multiple consecutive NIR exposures.
In addition to its use in light-triggered drug-delivery systems, the team stated, “We foresee multiple applications such as light-activated, self-healing capsules, extracellular scaffolds (nanofibers and hydrogels) providing on-demand delivery of cues for cell proliferation, differentiation or migration, and activatable fluorescent particles based on thermochromic dyes.”
– Written by Kasumi Crews
Source: Viger ML, Sheng W, Dore K et al. Near infrared-induced heating of confined water in polymeric particles for efficient payload release. ACS Nano. doi:10.1021/nn500702g (2014) (Epub ahead of print).
Nanosensor Screening to Detect Drug-Related Damage
Nanoparticle-based sensor developed for in vivo, real-time detection of drug-induced hepatotoxicity
Scientists at Stanford University (CA, USA) have developed a nanosensor capable of detecting drug-induced hepatotoxicity in real time. Liver toxicity is a leading cause of drug failure, therefore the detection of oxidative stress markers, reactive oxygen species (ROS) and reactive nitrogen species (RNS) could help to streamline the drug-development process. However, until now, direct measurement of these metabolites in the liver has not been easy. Led by Jianghong Rao, researchers have developed nanoparticle-based sensors that can directly detect ROS and RNS in animal livers.
The sensors, based on chemiluminescence–fluorescence semiconducting polymer nanoparticles, include two small organic molecules: one that detects ROS by emitting light when in contact with hydrogen peroxide and the other that detects RNS by changing its fluorescence signal when in contact with peroxynitrite. The sensors were tested in mice, using acetaminophen and isoniazid, and the light-emitting nanoparticles could be seen outside of the animals.
This technique was demonstrated to be useful for detecting toxicity in animals; however, it would not yet be suitable for use in humans due to the light not being able to penetrate the greater depth of the human liver. This could be overcome through the use of MRI and PET. The scientists hope that detecting liver toxicity will result in fewer toxic drugs and therefore improved success rate in clinical trials.
– Written by Lisa Parks
Source: Shuhendler A, Pu K, Li C, Uetrecht J, Rao J. Real-time imaging of oxidative and nitrosative stress in the liver of live animals for drug-toxicity testing. Nat. Biotechnol. 32(4), 373–380 (2014).
Wearable Nanoparticle-Based Devices Could Have Potential Clinical Applications
A collaborating group of researchers from South Korea and the USA has recently reported the development of new technology for wearable devices with potential clinical applications.
The devices incorporate arrays of single crystal silicon and inorganic solid-state sensors, such as strain gauges or temperature sensors and actuators (e.g., resistive heaters), coupled with uniform-sized, energy-efficient nanoparticles for portable data storage and nanoparticle-based drug-release mechanisms responsible for transdermal drug delivery.
Speaking to Nanomedicine, Dae-Hyeong Kim, senior author of the study, commented: “This is novel breakthrough in real-time monitoring of a patient's condition, point-of-care diagnosis based on the stored data, and controlled drug delivery through the skin.” There is an increasing need for devices that combine data collection with drug delivery. However, the development of wearable healthcare devices that have the ability to quantitatively track disease progression, store data and can offer controlled therapeutic delivery via the skin is an area that is still under development.
Integrating the therapeutic components with electronics has so far posed a great challenge, especially with regard to the data storage module and the transdermal drug-delivery mechanism. Kim commented, “This platform would require new research and development in transdermally deliverable drugs,” when asked about the therapeutic implications of this discovery.
When discussing future applications of this technology, Kim explained, “We need to include the power supply and wireless data transmission units. This integration will enable this system to run independently without the help of external wearable devices. A remote diagnosis and therapy is another important new application with above improvements.”
– Written by Evgenia Koutsouki
Source: Son D, Lee J, Qiao S et al. Multifunctional wearable devices for diagnosis and therapy of movement disorders. Nat. Nanotech. 9(5), 397–404 (2014).
Intranasal Peptide Delivery Demonstrates Antidepressant-Like Effect
A study outlining the intranasal administration of a peptide that relieves symptoms of depression has been published
Researchers at the Centre for Addiction and Mental Health (ON, Canada) have investigated the use of a nasal spray to deliver a peptide that has shown antidepressant-like effects. Their results suggest that this is a promising treatment option for patients with major depressive disorder.
Fang Liu, who led the team conducting the research, had previously observed that the binding of D1 and D2 receptors was higher in the brains of people with major depressive disorder, and developed a peptide that disrupts this interaction. The findings of this study were published in Nature Medicine in 2010, and describe how when injected into the brain, the peptide was just as effective in relieving symptoms compared with a conventional antidepressant in an animal model. In order to be clinically viable, it was necessary to seek an effective, noninvasive delivery route.
Following investigation into alternative administration routes, the team have now demonstrated delivery of the peptide to relevant brain areas using a nasal delivery system developed by Impel NeuroPharma (WA, USA) called the Pressurized Olfactory Device. Intranasal administration of the peptide had a significant antidepressant-like effect in the forced swimming test, a common preclinical test for antidepressant efficacy.
“This study marks the first time a peptide treatment has been delivered through nasal passageways to treat depression,” commented Liu. Encouraged by the results, the team is exploring the possibility of improving the therapeutic effects of the peptide by making it break down more slowly and traveling quicker in the brain.
– Written by Kasumi Crews
Sources: Brown V, Liu F. Intranasal delivery of a peptide with antidepressant-like effect. Neuropsychopharmacology doi:10.1038/npp.2014.61 (2014) (Epub ahead of print); Nasal spray delivers new type of depression treatment.http://www.camh.ca/en/hospital/about_camh/newsroom/news_releases_media_advisories_and_backgrounders/current_year/Pages/Nasal-spray-delivers-new-type-of-depression-treatment.aspx