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Highlighting the latest news in nanomedicine
Electrically controlled drug-delivery system may help minimize side effects Remotely controlled drug-delivery device may be a step towards ‘smart’ closedloop drug-eluting systems
Researchers from the University of Pittsburgh (PA, USA) have developed an electrically controlled drug-delivery nanocomposite that is able to release the drug on-demand in response to voltage stimulation. The nanocomposite comprises graphene oxide (GO) deposited inside a conducting polymer scaffold, which was found to exhibit favorable electrical properties. The team loaded the drug-delivery system with anti-inflammatory molecule, dexamethasone. When voltage stimulation was applied, the nanocomposite was found to release the drug with a linear release profile at a dosage that could be adjusted by varying the magnitude of stimulation. In the absence of stimulation, it was observed that the drug did not passively diffuse from the composite. The group, which was led by Xinyan Tracy Cui, Associate Professor at the University of Pittsburgh, reported that they were
able to tailor the properties of the delivery system by decreasing the size and thickness of the GO nanosheets, which in turn influenced drug loading and release profiles. In addition, in vitro cell culture experiments demonstrated that the released drug retained its bioactivity and that no toxic by-products were leached from the film during electrical stimulation. According to the team, previous versions of the drug release system were severely limited by a finite drug-loading capacity. However, with the addition of the GO nanosheets to the nanocomposite material it was found that the amount of drug that could be released from the system significantly improved, thereby widening the therapeutic range of the device and potentially increasing its lifespan. Commenting on the significance of the results, Cui explained that, conventionally,
part of
10.2217/NNM.14.46 © 2014 Future Medicine Ltd
Nanomedicine (2014) 9(5), 569–571
ISSN 1743-5889
569
News & views News drugs are delivered systemically (e.g., orally or intravenously), at a dose that is much higher than that which is required to have a therapeutic effect at the target tissue, often resulting in adverse side effects. Cui commented: “With our on-demand delivery system, these side effects may be avoided because we will be able to release the drug selectively into the target tissue, with a high level of control over the timing of delivery and the magnitude of the dose.”
Speaking to Nanomedicine, Cui commented that, in terms of future work the team intends to, they will “continue investigating the ability of the GO nanosheets to finely modulate the dosing range of the drug delivery system.” The team also plans to study the sensing capability of the composite to detect various biomarkers or neural signals. “Eventually, we wish to build a close-loop system, which detects a condition and release treatment accordingly,” said Cui.
– Written by Hannah Coaker Source: Weaver CL, Larosa JM, Luo X, Cui XT. Electrically controlled drug delivery from graphene oxide nanocomposite films. ACS Nano 8(2), 1834–1843 (2014).
Nanodiamond-embedded contact lenses for glaucoma treatment: a different sort of twinkle in your eye? Glaucoma, which affects approximately one in 200 individuals aged 50 years and below, is a disease that, if left untreated, can damage the optic nerve and lead to blindness. Current treatment schedules include the administration of eye drops; however, their effectiveness is limited by a lack of sustained drug delivery and poor patient compliance. Now, a team of researchers from the UCLA School of Dentistry (CA, USA) have developed a drug-delivery system that demonstrates potential in glaucoma treatment by reducing side effects and improving patient compliance. Led by Dean Ho, Professor of Oral Biology and Medicine at UCLA, the group created contact lenses embedded with nanodiamonds that are bound to glaucoma drugs. These drugs are then released following exposure to an enzyme (lysozyme) found in tears. The scientists report that the nanoscale treatment demonstrates controlled and sustained release in the presence of lysozyme, and even improves the contact lenses’ durability. Speaking to Nanomedicine, Ho explained the results’
significance: “There have recently been exciting developments in the area of drug delivery for glaucoma, including a recent study that demonstrated release for at least 1 month, which was a great achievement. Our goal here was to take the nanodiamond platform, which is essentially a byproduct of conventional mining/refining and potentially a sustainable nanomaterial as it can be treated and processed in a facile manner to yield uniform particles, and create a new lens with improved properties and triggered drug release capabilities.” Discussing the implications for future research in this area, Ho said: “Our work, along with others in this field, may improve the consistency of dosing for glaucoma patients since dosing is hard to control with eyedrops due to leakage out of the eye, and compliance is a challenge that often results in vision loss. Enabling drug release via a contact lens could markedly improve compliance.” The scientists now hope to validate their results in animal models, and to optimize drug loading and dosing duration.
– Written by James Potticary Sources: Kim HJ, Zhang K, Moore L, Ho D. Diamond nanogel-embedded contact lenses mediate lysozyme-dependent therapeutic release. ACS Nano doi:10.1021/nn5002968 (2014) (Epub ahead of print); UCLA press release: http://newsroom.ucla.edu/portal/ ucla/nanodiamond-embedded-contact-lenses-250078.aspx
Rapamycin-loaded nanoparticles offer potential new treatment for muscular dystrophy A team of scientists at Washington University School of Medicine in St Louis (MO, USA) have reported a new, nanoparticle-based approach to treat muscular dystro-
570
Nanomedicine (2014) 9(5)
phy. Demonstrated in a mouse model of Duchenne muscular dystrophy, the most severe inherited form of the disease, the investigators delivered nanoparticle-loaded
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News
formulations of rapamycin, an immunosuppressive drug that improves recycling of cellular waste. Duchenne muscular dystrophy, which solely affects boys, causes the majority of sufferers to be wheelchair dependent by the age of 12, with an average life expectancy of 25 years. The disorder is characterized by a faulty gene that consequently prevents the body from producing dystrophin, a protein that is crucial for maintaining muscle cell integrity and function. While it is not clear how this missing protein is responsible for maintaining muscle cell integrity, the researchers demonstrated that the mice suffering from the disease cannot recycle cellular waste, a mechanism known as autophagy. By boosting this self-eating process, the mice showed improved skeletal muscle strength and function. Specifically, when treated with the rapamycin- loaded nanoparticles, the mice showed a 30% increase in grip strength and a notable improvement in cardiac function.
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Samuel Wickline, senior author of the study, commented, “Autophagy plays a major role in disposing of cellular debris. If it doesn’t happen, you might say the cell chokes on its own refuse. In muscular dystrophy, defective autophagy is not necessarily a primary source of muscle weakness, but it clearly becomes a problem over time. If you solve that, you can help the situation by maintaining more normal cellular function.” Typically used to help prevent organ rejection in transplant patients, rapamycin is known for its anti-inflammatory properties and role in activating autophagy. “The nanoparticles tend to penetrate and be retained in areas of inflammation,” Wickline explained. “Then they release the rapamycin over a period of time, so the drug itself can permeate the muscle tissue.” Current treatment for muscular dystrophy results in a modest increase in strength; however, long-term side effects mean that there is a need for a more effective treatment.
– Written by James Potticary Sources: Bibee KP, Cheng YJ, Ching JK et al. Rapamycin nanoparticles target defective autophagy in muscular dystrophy to enhance both strength and cardiac function. FASEB J. doi:10.1096/fj.13-237388 (2014) (Epub ahead of print); Washington University in St Louis press release: https://news.wustl.edu/news/Pages/26497.aspx
Researchers hijack migration of brain cancer cells using polycaprolactone-based nanofibers A collaborative research team has reported a novel approach to enhance the treatment of glioblastoma multiforme, an aggressive and invasive brain tumor that is associated with poor survival rates. This particular tumor is known to invade and migrate through the brain along white matter tracts and blood vessels. The team has designed a system that exploits this migratory pathway that is characteristic of glioblastoma multiforme by engineering aligned polycaprolactone (PCL)-based nanofibers that attach to the tumor cells and, in doing so, guide them from the primary tumor site to an extracortical location. This extracortial sink is a cyclopamine drug-conjugated, collagen-based hydrogel. The team found that when aligned PCL nanofiber films in a PCL/polyurethane carrier conduit were inserted in the vicinity of an intracortical human U87MG glioblastoma xenograft, a significant number of human glioblastoma cells migrated along the
aligned nanofiber films and underwent apoptosis in the extracortical hydrogel. Results of the study also indicated that tumor volume in the brain was significantly lower following insertion of aligned nanofiber implants compared with the application of smooth fibers or no implants. Ravi Bellamkonda, lead investigator and Chair at Georgia Institute of Technology (GA, USA) and Emory University (GA, USA), envisages that the new technique may be able to control the growth of inoperable cancers, allowing patients to live normal lives despite the disease. “If we can provide cancer an escape valve of these fibers, that may provide a way of maintaining slow-growing tumors such that, while they may be inoperable, people could live with the cancers because they are not growing,” said Bellamkonda. The team now intends to evaluate the technique with other forms of brain cancer, and other types of cancer that can be difficult to remove.
– Written by Hannah Coaker Source: Jain A, Betancur M, Patel GD et al. Guiding intracortical brain tumour cells to an extracortical cytotoxic hydrogel using aligned polymeric nanofibres. Nat. Mater. 13(3), 308–316 (2014).
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www.futuremedicine.com
571
Highlighting the latest news in nanomedicine
Electrically controlled drug-delivery system may help minimize side effects Remotely controlled drug-delivery device may be a step towards ‘smart’ closedloop drug-eluting systems
Researchers from the University of Pittsburgh (PA, USA) have developed an electrically controlled drug-delivery nanocomposite that is able to release the drug on-demand in response to voltage stimulation. The nanocomposite comprises graphene oxide (GO) deposited inside a conducting polymer scaffold, which was found to exhibit favorable electrical properties. The team loaded the drug-delivery system with anti-inflammatory molecule, dexamethasone. When voltage stimulation was applied, the nanocomposite was found to release the drug with a linear release profile at a dosage that could be adjusted by varying the magnitude of stimulation. In the absence of stimulation, it was observed that the drug did not passively diffuse from the composite. The group, which was led by Xinyan Tracy Cui, Associate Professor at the University of Pittsburgh, reported that they were
able to tailor the properties of the delivery system by decreasing the size and thickness of the GO nanosheets, which in turn influenced drug loading and release profiles. In addition, in vitro cell culture experiments demonstrated that the released drug retained its bioactivity and that no toxic by-products were leached from the film during electrical stimulation. According to the team, previous versions of the drug release system were severely limited by a finite drug-loading capacity. However, with the addition of the GO nanosheets to the nanocomposite material it was found that the amount of drug that could be released from the system significantly improved, thereby widening the therapeutic range of the device and potentially increasing its lifespan. Commenting on the significance of the results, Cui explained that, conventionally,
part of
10.2217/NNM.14.46 © 2014 Future Medicine Ltd
Nanomedicine (2014) 9(5), 569–571
ISSN 1743-5889
569
News & views News drugs are delivered systemically (e.g., orally or intravenously), at a dose that is much higher than that which is required to have a therapeutic effect at the target tissue, often resulting in adverse side effects. Cui commented: “With our on-demand delivery system, these side effects may be avoided because we will be able to release the drug selectively into the target tissue, with a high level of control over the timing of delivery and the magnitude of the dose.”
Speaking to Nanomedicine, Cui commented that, in terms of future work the team intends to, they will “continue investigating the ability of the GO nanosheets to finely modulate the dosing range of the drug delivery system.” The team also plans to study the sensing capability of the composite to detect various biomarkers or neural signals. “Eventually, we wish to build a close-loop system, which detects a condition and release treatment accordingly,” said Cui.
– Written by Hannah Coaker Source: Weaver CL, Larosa JM, Luo X, Cui XT. Electrically controlled drug delivery from graphene oxide nanocomposite films. ACS Nano 8(2), 1834–1843 (2014).
Nanodiamond-embedded contact lenses for glaucoma treatment: a different sort of twinkle in your eye? Glaucoma, which affects approximately one in 200 individuals aged 50 years and below, is a disease that, if left untreated, can damage the optic nerve and lead to blindness. Current treatment schedules include the administration of eye drops; however, their effectiveness is limited by a lack of sustained drug delivery and poor patient compliance. Now, a team of researchers from the UCLA School of Dentistry (CA, USA) have developed a drug-delivery system that demonstrates potential in glaucoma treatment by reducing side effects and improving patient compliance. Led by Dean Ho, Professor of Oral Biology and Medicine at UCLA, the group created contact lenses embedded with nanodiamonds that are bound to glaucoma drugs. These drugs are then released following exposure to an enzyme (lysozyme) found in tears. The scientists report that the nanoscale treatment demonstrates controlled and sustained release in the presence of lysozyme, and even improves the contact lenses’ durability. Speaking to Nanomedicine, Ho explained the results’
significance: “There have recently been exciting developments in the area of drug delivery for glaucoma, including a recent study that demonstrated release for at least 1 month, which was a great achievement. Our goal here was to take the nanodiamond platform, which is essentially a byproduct of conventional mining/refining and potentially a sustainable nanomaterial as it can be treated and processed in a facile manner to yield uniform particles, and create a new lens with improved properties and triggered drug release capabilities.” Discussing the implications for future research in this area, Ho said: “Our work, along with others in this field, may improve the consistency of dosing for glaucoma patients since dosing is hard to control with eyedrops due to leakage out of the eye, and compliance is a challenge that often results in vision loss. Enabling drug release via a contact lens could markedly improve compliance.” The scientists now hope to validate their results in animal models, and to optimize drug loading and dosing duration.
– Written by James Potticary Sources: Kim HJ, Zhang K, Moore L, Ho D. Diamond nanogel-embedded contact lenses mediate lysozyme-dependent therapeutic release. ACS Nano doi:10.1021/nn5002968 (2014) (Epub ahead of print); UCLA press release: http://newsroom.ucla.edu/portal/ ucla/nanodiamond-embedded-contact-lenses-250078.aspx
Rapamycin-loaded nanoparticles offer potential new treatment for muscular dystrophy A team of scientists at Washington University School of Medicine in St Louis (MO, USA) have reported a new, nanoparticle-based approach to treat muscular dystro-
570
Nanomedicine (2014) 9(5)
phy. Demonstrated in a mouse model of Duchenne muscular dystrophy, the most severe inherited form of the disease, the investigators delivered nanoparticle-loaded
future science group
News
formulations of rapamycin, an immunosuppressive drug that improves recycling of cellular waste. Duchenne muscular dystrophy, which solely affects boys, causes the majority of sufferers to be wheelchair dependent by the age of 12, with an average life expectancy of 25 years. The disorder is characterized by a faulty gene that consequently prevents the body from producing dystrophin, a protein that is crucial for maintaining muscle cell integrity and function. While it is not clear how this missing protein is responsible for maintaining muscle cell integrity, the researchers demonstrated that the mice suffering from the disease cannot recycle cellular waste, a mechanism known as autophagy. By boosting this self-eating process, the mice showed improved skeletal muscle strength and function. Specifically, when treated with the rapamycin- loaded nanoparticles, the mice showed a 30% increase in grip strength and a notable improvement in cardiac function.
News & views
Samuel Wickline, senior author of the study, commented, “Autophagy plays a major role in disposing of cellular debris. If it doesn’t happen, you might say the cell chokes on its own refuse. In muscular dystrophy, defective autophagy is not necessarily a primary source of muscle weakness, but it clearly becomes a problem over time. If you solve that, you can help the situation by maintaining more normal cellular function.” Typically used to help prevent organ rejection in transplant patients, rapamycin is known for its anti-inflammatory properties and role in activating autophagy. “The nanoparticles tend to penetrate and be retained in areas of inflammation,” Wickline explained. “Then they release the rapamycin over a period of time, so the drug itself can permeate the muscle tissue.” Current treatment for muscular dystrophy results in a modest increase in strength; however, long-term side effects mean that there is a need for a more effective treatment.
– Written by James Potticary Sources: Bibee KP, Cheng YJ, Ching JK et al. Rapamycin nanoparticles target defective autophagy in muscular dystrophy to enhance both strength and cardiac function. FASEB J. doi:10.1096/fj.13-237388 (2014) (Epub ahead of print); Washington University in St Louis press release: https://news.wustl.edu/news/Pages/26497.aspx
Researchers hijack migration of brain cancer cells using polycaprolactone-based nanofibers A collaborative research team has reported a novel approach to enhance the treatment of glioblastoma multiforme, an aggressive and invasive brain tumor that is associated with poor survival rates. This particular tumor is known to invade and migrate through the brain along white matter tracts and blood vessels. The team has designed a system that exploits this migratory pathway that is characteristic of glioblastoma multiforme by engineering aligned polycaprolactone (PCL)-based nanofibers that attach to the tumor cells and, in doing so, guide them from the primary tumor site to an extracortical location. This extracortial sink is a cyclopamine drug-conjugated, collagen-based hydrogel. The team found that when aligned PCL nanofiber films in a PCL/polyurethane carrier conduit were inserted in the vicinity of an intracortical human U87MG glioblastoma xenograft, a significant number of human glioblastoma cells migrated along the
aligned nanofiber films and underwent apoptosis in the extracortical hydrogel. Results of the study also indicated that tumor volume in the brain was significantly lower following insertion of aligned nanofiber implants compared with the application of smooth fibers or no implants. Ravi Bellamkonda, lead investigator and Chair at Georgia Institute of Technology (GA, USA) and Emory University (GA, USA), envisages that the new technique may be able to control the growth of inoperable cancers, allowing patients to live normal lives despite the disease. “If we can provide cancer an escape valve of these fibers, that may provide a way of maintaining slow-growing tumors such that, while they may be inoperable, people could live with the cancers because they are not growing,” said Bellamkonda. The team now intends to evaluate the technique with other forms of brain cancer, and other types of cancer that can be difficult to remove.
– Written by Hannah Coaker Source: Jain A, Betancur M, Patel GD et al. Guiding intracortical brain tumour cells to an extracortical cytotoxic hydrogel using aligned polymeric nanofibres. Nat. Mater. 13(3), 308–316 (2014).
future science group
www.futuremedicine.com
571
