Improved drug-delivery nanoparticles penetrate brain
Advanced drug-delivery nanoparticles hold significant promise for the treatment of brain cancer and other maladies of this organ
Researchers at the Johns Hopkins Center for Nanomedicine (MD, USA) have made a step towards the development of a drug-delivery system capable of overcoming some of the key challenges posed by diseases of the brain. The team of bioengineers has designed nanoparticles that demonstrate the ability to safely and predictably infiltrate deep into the brain, serving as vectors for tumor-directed drug delivery.
In accordance with standard treatment protocol, following brain tumor surgery, chemotherapy is applied directly to the site of removal to treat cancerous cells that failed to be surgically removed. Preventing tumor recurrence in this way, affords a moderate success rate, partially due to the inherent difficulty of administering a dose of chemotherapy that is both safe as well as effective. To address this dosage challenge, engineers designed nanoparticles that are capable of delivering chemotherapy in small, steady quantities over a period of time.
Conventional drug-delivery nanoparticles consist of entrapped drug molecules and microscopic, string-like molecules, which, together, form a tight ball. The nanoparticles, upon contact with water, breakdown slowly to release the drug.
The major issue of conventional nanoparticles is that they typically “stick to cells at the application site and tend not to migrate deeper into the tissue,” says Charles Eberhart, a pathologist at the John Hopkins Center and contributor to this work. Subsequently, tumor cells, which have escaped the tumor mass, are not targeted by the therapy.
Members of the research team, Elizabeth Nance and Graeme Woodworth, conjectured that by ensuring minimal interaction of the drug-delivery nanoparticles with their surroundings, drug penetration might be improved. To test their hypothesis, nano-sized plastic beads of various sizes were coated with PEG, which is known protect nanoparticles from the body‘s defence mechanisms and was also anticipated to make the beads more slippery, improving ease of diffusion.
The coated beads were labeled with luminous tags and their movement tracked following injection into slices of rodent and human brain tissue. In comparison to non-PEG-coated beads and beads with a thinner coating of PEG, a dense coating of PEG was found to significantly enhance diffusion of the beads through tissue, to the extent that beads twice the size of the previously accepted maximum penetrated within the brain. The equivalent test on live rodent brains yielded the same results.
The team then took biodegradable nanoparticles, carrying the chemotherapy drug paclitaxel, and coated them with PEG. In conjunction with initial tests, the PEG-covered nanoparticles exhibited improved distribution within the rat brain tissue, relative to nanoparticles without the coating, which moved very little.
“We now have particles that can carry five-times more drug, release it three-times as long and penetrate farther into the brain than before,” says Nance. “The next step is to see if we can slow tumor growth or recurrence in rodents.” Woodworth added that the team “also wants to optimize the particles and pair them with drugs to treat other brain diseases, such as multiple sclerosis, stroke, traumatic brain injury, Alzheimer‘s and Parkinson‘s disease.” At present, the team is conducting research into administering their nanoparticles intravenously.
– Written by Hannah Coaker
Source: Nance EA, Woodworth GF, Sailor KA et al. A dense poly(ethylene glycol) coating improves penetration of large polymeric nanoparticles within brain tissue. Sci. Transl. Med. 4(149), 147–158 (2012).
West to develop and market SelfDose™ technology following deal with Janssen
West Pharmaceutical Services (PA, USA) has announced a deal with Janssen Biotech (PA, USA), a pharmaceutical company of Johnson & Johnson, to collaborate on developing and manufacturing an innovative self-injection product. The technology, known as SelfDose™ was developed by Janssen to make the self-injection of pharmaceutical and biologic drug products easier for patients.
West, which made US$1.2 billion sales in 2011, will be responsible for the co-development, commercial scale-up and also manufacture of the SelfDose system to enable safe, effective and reliable delivery of medication. The product accompanies West‘s other self-injection technologies, ConfiDose® and SmartDose®, and expands the companies investigation of new products in the market.
Donald Morel Jr, Chairman and CEO of West commented, “We are delighted to have formalized our relationship with Janssen around this drug-delivery platform and look forward to working together to commercialize the SelfDose injection technology, providing manufacturing, development and regulatory support through the remainder of the process.”
Regarding the future of the partnership, Morel added that West, “values the opportunity to strengthen our long-standing relationship and are excited by this agreement. We look forward to working with Janssen to help them meet their business goals to restore health and serve patients.”
– Written by James Potticary
Source: West Pharmaceutical Services Press Release: www.westpharma.com/en/Investors/Pages/NewsReleases.aspx?reqtype=releasetxt&reqid=1731010
Micromotors with built-in compasses have potential for drug delivery
Research teams at Nanyang Technological University (Singapore) and the Leibniz Institute for Solid State and Materials Research (Dresden, Germany) have designed micromotors with a view for application in highly targeted drug delivery.
The research demonstrates for the first time that iron-containing rolled-up microtubular engines can be permanently magnetized, acting as compass needles and sensing the direction of an external magnetic field in similar fashion to magnetotactic bacteria. Consequently, the magnetized microjets can be attracted to or repulsed from the external magnetic field, bringing a new level of control to how the directions of such microjets can be manipulated.
Speaking to Therapeutic Delivery, Martin Pumera, who led the Singapore-based team explained, “The devices can navigate themselves in a weak magnetic field and they propel themselves as well. There is no other technology able to do so. Our devices can be remotely controlled from far away and they can propel themselves to deliver the proper drug to the point of interest.”
The microjet structures consist of a layered structure of titanium, iron, chromium and platinum. Using hydrogen peroxide solution as a fuel, they produced a propelling jet of oxygen bubbles and direction was controlled upon the application of the external magnetic field.
The research groups will be continuing their work towards targeted drug delivery with nanomotors. “We are currently developing chemosensing nanomotors that will be able to find the malicious cell and destroy it without any external navigation,” Pumera stated.
– Written by James Potticary
Source: Zhao G, Sanchez S, Schmidt OG et al. Micromotors with built in compasses. Chem. Commun. 48(81), 10090–10092 (2012).
Approach to protein imaging has implications for the future of drug delivery
Scientists from Arizona State University (AZ, USA) have devised a new technique for examining the binding kinetics of membrane proteins, which will provide unique information regarding their interaction with drugs.
The group, led by Nongjian Tao, Director of the Center for Bioelectronics and Biosensors at Arizona State University‘s Biodesign Institute (AZ, USA) show that the technique, known as surface plasmon resonance (SPR) microscopy, has the potential to greatly simplify the study of membrane proteins and consequently simplify the drug-design process.
Current techniques do not always accurately study binding kinetics due to techniques such as extraction, which often result in the protein in question losing its characteristics. The new technique allows for in situ investigation using SPR to provide high-resolution spatial and temporal information while also allowing for simultaneous optical and fluorescence observation of the sample.
Speaking to Therapeutic Delivery, Tao commented on the advantages, “The work demonstrates a new approach to study membrane proteins of single living cells. It is label-free, capable of resolving spatial distribution of membrane proteins on a cell, and compatible with conventional optical and fluorescence imaging techniques.”
Specifically, regarding the implications for the future of drug discovery and delivery, Tao explained, “Since the majority of drug targets are membrane proteins, we anticipate that the plasmonic imaging technique will be used for fast screening of drug candidates and provide unique kinetic information about the drug-membrane protein interactions.”
The research group now intend to take advantage of the versatility of SPR microscopy, “We are currently integrating it with other imaging techniques, including fluorescence, with an aim at combining the strengths of label and label-free detection methods,” said Tao.
– Written by James Potticary
Source: Wang W, Yang Y, Wang S et al. Label-free measuring and mapping of binding kinetics of membrane proteins in single living cells. Nat. Chem. 4(10), 846–853 (2012).
The emergence of the male contraceptive pill
A team of researchers has discovered a compound that is proposed to become a male version of the contraceptive pill. The study outlines that a compound called JQ1 had a “complete and reversible contraceptive effect” in mice.
JQ1 functions by directly inhibiting bromodomain activity of the testes-specific protein BRDT, which is essential for chromatin remodelling during spermatogenesis. The resulting effect was the reduction of sperm production and motility, without altering hormone levels. This may prove to provide an advantage over the female contraceptive pill, which can interfere with hormone levels, in particular estrogen.
Qinglei Li, Assistant Professor at Texas A&M University (TX, USA) who was part of the research team on the project commented of JQ1, “It stopped the sperm production very dramatically. More good news is that there appears to be no side effects whatsoever. Once the JQ1 was no longer given to the mice, they were back to their normal reproduction rates, and it did not affect mating behavior or the health of the offspring.”
The research team is now creating and testing the effects of JQ1 derivatives with selectivity in order to extend the therapeutic window of the compound. Furthermore, the researchers state that inhibitory compounds with increased affinity and selectivity for BRDT “would be expected to reduce any possible long-term, adverse effects.” Li emphasized this point, stating, “A compound with more specificity will be needed before clinical trials can be done for humans. It does not mean a male birth control just yet, but it is a great step forward in that direction”.
– Written by James Potticary
Sources: Matzuk MM, McKeown MR, Filippakopoulos P et al. Small-molecule inhibition of BRDT for male contraception. Cell 150(4), 673–784 (2012).