What’s up in nanomedicine?
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Georgette B. Salieb-Beugelaar
The publications discussed here are selected exemplarily among many other excellent publications. This also applies for the mentioned conferences or events. We very much appreciate your feedback on the column, suggestions for topics to be argued about, or other related information. As was already stated, the purpose of this column is to present novel and significant developments within the multidisciplinary field of nanomedicine or significant developments in other scientific areas.
Publications digest
Ultrasound-induced blood-brain-barrier opening and drug delivery
The use of focused ultrasound (FUS) to open the blood-brain barrier (BBB) had already showed to be promising for the targeted delivery of drugs (1, 2). Studies have shown that the physicochemical properties of the microbubbles and acoustic energy applied during sonication (3, 4) is linked to the extent of the BBB opening. In this work of Chen and coworkers (5), nanodroplets were presented as a new class of contrast agents to mediate FUS induced opening of the BBB and it was investigated whether these nanodroplets are feasible for targeted drug delivery in the brain. To the knowledge of the authors, this is the first study that explored the benefits of a nanodroplet-based approach to FUS induced BBB opening. As a standard for comparing the efficiency of the BBB opening based on the delivery of the dextran molecules in vivo, in-house generated microbubbles were used with the same perfluorocarbon gaseous core and the same lipid shell composition. Microbubbles were developed using 1,2-distearoyl-sn-3-phosphocholine and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy (polyethylene glycol) 2000] (DSPE-PEG2000) in the ratio 90:10 mol%. As a contrast agent perfluorobutane (PFB) gas was used. The investigators found that the core of the nanodroplets can be both in liquid or gaseous states. They further observed that contrast agent influences the threshold at which the dextran delivery occurs. In another investigation, Choi et al. (6) showed that short ultrasonic pulses enable the homogenous distribution of dextran molecules (3 kDa). Chen and coworkers (5) showed that with the nanodroplets, similar homogenous dextran distribution could be provided when using the same acoustic exposure settings. They observed that in the mouse hippocampus the fluorescence was diffusely distributed. The method is therefore promising for the delivery of therapeutic agents to cellular targets outside the microvasculature.
Nanochannels for universal, zero-order drug delivery
Ferrati and coworkers (7) presented an implantable nanochannel membrane that achieves a constant drug delivery in vivo. In this investigation, a novel design algorithm is used to select the optimal nanochannel dimensions for achieving zero-order release kinetics of each selected drug. In this model, the drug molecule is first classified as a nanoparticle, polymer (peptides, proteins or long/short biopolymers) or a small molecule (<850 kDa). Subsequently the molecule is determined upon water solubility and the valence charge. The algorithm provides a nanochannel height-to-drug ratio, which ensures the constant release of the drug. Ferrati et al. (7) proved the functionality of these nanochannels by using nanochannels of 3.6 nm and 20 nm for the sustained and constant plasma levels of human growth hormone (hGH), octreotide (OCT), leuprolide (LEUP), interferon α-2b (INF α-2b), Y-27632 and letrozole (LETR). The selected therapeutic agents represent a broad range of treatments. LEUP, LETR, INF α-2b and OCT for cancer treatment, and in addition LETR and INF α-2b also for chemoprevention and infectious diseases respectively. Then finally, hGH for hormone replacement and Y-27632 for transplantation. All the drugs were delivered at clinical relevant doses. After determination of the drugs in vitro by using UV-spectroscopy, the in vivo experiments were performed. Nanochannel membranes were manufactured and assembled in implantable capsules (discoidal or cylindrical) and the drugs were loaded in the membrane capsule in an aqueous solution or in solid form (powders). The capsules were subcutaneously implanted in three animal models (mice, rats and dogs) and the constant and sustained delivery of therapeutically relevant doses were validated. To prove the potency of this novel method, a nanochannel implant in a rat model was employed to prevent chronic rejection of cardiac allograft by the constant and long-term delivery of Y-27632. Finally, Ferrati and coworkers (7) proved that the implants are biocompatable and safe to use. No abnormal wound healing or tissue reactions to the implants or adverse immune reactions were observed. In addition, the cylindrical implants showed also to be more mechanically resistant when comparing to existing implantable systems.
Nanocaged POSS-PCU scaffolds
POSS-PCU is a nanocomposite based on polyhedral oligomeric silsesquioxanes [POSS, (RSiO3/2)n] and poly(carbonate-urea)urethane (PCU). POSS has a cage-like structure while PUC gives the material hydrolytic and oxidative stability in vitro (8, 9). Due to the mechanical properties and a lack of degradation, this material might be ideal for developing synthetic heart valves and aortic stent-grafts (10, 11). The material has already undergone full toxicology assessment and even been used in applications inside humans, however there is very little known about how well these scaffold supports cellularization and differentiation of human stem cells with chondrogenic potential. Guasti and coworkers (12) developed novel bionanoscaffolds using POSS-PCU and pediatric adipose tissue-derived stem cells (hADSCs). In another investigation of these authors (13), the highly reproducible behavior of these cells grown from pediatric patients affected by craniofacial disorders and their high plasticity was reported. The ability of the hADSCs to undergo chondrogenic differentiation in nanoscaffolds with the suitable mechanical strength for use in the reconstruction of craniafacial cartilages was of importance in this investigation. The behavior of hADSCs and chondroblasts were analysed when grown on plastic, on two-dimensional and non-coagulated POS-PCU and on POSS-PCU three-dimensional (3D) scaffolds of controlled pore size and porosity. It was evaluated whether the POSS-PCU affects the chondrogenic differentiation capability. The investigators found that POSS-PCU offers excellent bioactivity and appropriate mechanical strength and that the hADSCs/POSS-PCU scaffolds could be rapidly surrounded by blood vessels. No apparent negative reaction was observed. Guasti and coworkers (12) suggested that these scaffolds might be of great value for several applications such as the improvement of tracheal transplants.
Nanodiamons-daunorubicin and multidrug resistance in leukemia
A major challenge in treatment of leukemia remains the development of multidrug chemoresistance (MDR) (14) that often occurs in patients that are initially responded well to the therapy (15). MDR is a general type of resistance that is often caused by ATP-binding cassette (ABC) transporter proteins, which are normally responsible for the transport of various compounds (such as lipids or metabolic products) across the cell membrane (16). By using nanoparticles, the drug is entering the cell through endocytosis and as a consequence the intracellular drug concentration can be increased, which might at the end improve treatment efficacy. Nanodiamonds (NDs) is a class of nanoparticles that has already shown both the delivery and the enhanced function of its payload (17). Man and coworkers investigated a novel therapeutic payload (18). NDs were developed such that daunorubicin (DNR) could be reversibly bound and released. The loading was optimized in different ways, such as the pH and drug-loading ratio. The investigators used as well molecular dynamic simulations of ND and DNR to confirm the release of DNR from the ND in the experimental results. They found that the drug release is increased at more acidic pH values. The efficacy of the ND was proved by the improved DNR delivery into resistant K562 cells, whereas the resistant K562 cells were able to overcome the treatment from DNR alone. With this, they demonstrated the potential to improve cancer treatment in particular regarding resistant strains. Man and coworkers (18) suggested that with the introduction of a gene therapy component, the expression of the proteins causing MDR might be actively reduced. NDs have already been investigated and showed excellent biocompatibility in vitro. Even though animal models with NDs conjugates that indicated excellent biological response and clearance (17, 19, 20), they recommended further investigation of the in vitro experiments in animal models to verify the safety of this delivery platform.
Upcoming events
In March (26th–28th) the 5th international BioNanoMed conference in Krems, Austria is held. This exclusive Know-How-Transfer meeting is attractive for scientists, engineers and practicers from a broad scientific area dedicated to biology, nanotechnology and medicine. Topics include, novel nanomedical solutions-advances in nanomedicine, nanomaterials for biomedical applications, nano-oncology, but also nanopharmaceuticals and production technologies. There are also thematical sessions, such as nanobiosensing or nanosafety. In addition, there will be a special symposium about nanotechnology in artifical organ support that is organized by The European Society of Artifical Organs (ESAO). For more information see also: http://www.bionanomed.at/
Also held from 26th to 27th of March is the Nanomedicine 2014 conference in Edinburgh, Scotland organized by the British Society of Nanomedicine (BSNM) in collaboration with SELECTBIO. The BSNM is a registered charity. One of the key aims of BSNM is the provision of forums for scientists that can be used to highlight their work or to publish their advances to the wider scientific community. SELECTBIO was initially started to provide scientific consultancy services to the biomedical industry. It offers now also services like organizing conferences or training courses to the life sciences marketplace and has the aim to advance disease research. Topics of this conference include aptamer-targeted nanoparticles, nanosuspensions, siRNA and biologicals and fundamental study of nanoparticle-biological interactions. For more information see http://selectbiosciences.com/conferences/index.aspx?conf=NMUK2014
Then, CLINAM 7/2014, the 7th European Summit for Clinical Nanomedicine and Targeted Medicine, the reference conference in Europe for the field. The summit will be held from June 22 to 25th in Basel and is organized by the European Foundation for Clinical Nanomedicine (CLINAM) and the European Technology Platform on Nanomedicine (ETPN). This indispensable worldwide platform brings together Clinical Nanomedicine and Targeted Medicine in the generic context with Personalized Medicine and the international debate platform on precise, highly effective novel spheres of Medicine. Next year’s focus topic is: Paving the Way to Personalized Diagnostics and Personalized Medicine. The conference is interesting for physicians, nanoscientists with a background in pharmacology, biology, physics, chemistry, biophysics, medicine materials science and engineering, developers of new tools and materials for nanomedicine but also for policymakers and experts from the industry in the life sciences. The summit includes clinical topics and sessions on technology, implications and on strategy, government and politics. For the call for posters and papers and the call for exhibitors see also: https://www.clinam.org/images/stories/pdf/call-13-1.pdf
References
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©2013 by Walter de Gruyter Berlin Boston
Artikel in diesem Heft
- Masthead
- Masthead
- Publication ethics and publication malpractice statement
- Editorial
- Nanomedicine enabled by computational sciences
- What’s up in nanomedicine?
- News from the European Foundation for Nanomedicine (CLINAM)
- Review
- Novel radioisotope-based nanomedical approaches
- Original Articles
- Silver nanowires as prospective carriers for drug delivery in cancer treatment: an in vitro biocompatibility study on lung adenocarcinoma cells and fibroblasts
- Plasmid linearization changes shape and efficiency of transfection complexes
- Opinion Paper
- Why healthcare open innovation is failing for nanomedicines
Artikel in diesem Heft
- Masthead
- Masthead
- Publication ethics and publication malpractice statement
- Editorial
- Nanomedicine enabled by computational sciences
- What’s up in nanomedicine?
- News from the European Foundation for Nanomedicine (CLINAM)
- Review
- Novel radioisotope-based nanomedical approaches
- Original Articles
- Silver nanowires as prospective carriers for drug delivery in cancer treatment: an in vitro biocompatibility study on lung adenocarcinoma cells and fibroblasts
- Plasmid linearization changes shape and efficiency of transfection complexes
- Opinion Paper
- Why healthcare open innovation is failing for nanomedicines
