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Nanoscale drug carriers bypass blood–brain barrier
NEWS
tiny fragments behind. The new dissolvable patch eliminates this risk, as the microneedles are designed to dissolve in the skin.
Materials Today Volume 18, Number 8 October 2015
‘‘We have shown that the patch is safe and that it works well. Since it is also painless and very easy for non-trained people to use, we think it could bring
about a major change in the way we administer vaccines globally,’’ said Professor Nakagawa. Lucy Goodchild
Nanoscale drug carriers bypass blood–brain barrier
NEWS
Treating brain cancers is difficult because of the blood–brain barrier (BBB), which protects the body’s most vital organ. This security system of blood vessels lined with tightly packed endothelial cells lets in essential nutrients, but keeps out foreign substances so effectively that the delivery of life-saving drugs is also blocked. But in a step towards overcoming the BBB, researchers from India and the USA have engineered the surface of nanosized polymeric drug carriers to bind onto cancer cells [Jain, et al., Acta Biomater. (2015), doi:10.1016/ j.actbio.2015.06.027]. While the BBB is very good at blocking large molecules from entering, much smaller and/or fat-soluble molecules are able to slip past the endothelial cell barrier. So the researchers, led by Vandana Soni at Dr Hari Singh Gour University in India and Thomas J. Webster at Northeastern University, designed a nanocarrier system based on poly (D,L-lactide-co-glycolide) (PGLA) nanoparticles coated with a water-soluble surfac-
tant, polysorbate 80, and loaded with a protein (transferrin, Tf) that binds onto cancer cells and an anticancer drug (methotrexate, Mtx). The other authors of the study are Neeraj K. Garg, Rajeev K. Tyagi, Atul Jain, Ashay Jain, Bhupinder Singh, and O.P. Katare. ‘‘To be an efficient delivery vehicle, polymeric nanocarriers must encompass multifunctional properties like biocompatibility, bio-distribution, non-toxicity, and be capable of overcoming biological barriers,’’ explains Tyagi. ‘‘[Our] nanoparticles are nanometric in range (200 nm) and lipophilic in nature, which helps them cross the BBB.’’ The protective polysorbate 80 coating helps the nanoparticles cross the BBB, while the addition of transferrin enables them to targets tumor cells and penetrate the cell membrane. Once in the brain, the combination also regulates the release of methotrexate, leading to long-lasting drug delivery. Importantly, the better targeting
of cancer cells reduces the dose of methotrexate received by other healthy cells. ‘‘Selective and targeted delivery of cytotoxic drugs towards malignant tumors might overcome loopholes with the existing therapeutic system when talking about brain cancer,’’ says Tyagi. ‘‘Polysorbate-80 coated polymeric nanoparticles conjugated with Tf-Mtx not only provide specific targeting across the BBB, but also suppress possible adverse effects in peripheral normal tissues/cells.’’ In tests with rats, the surface-engineered nanoparticles led to higher cellular uptake of the methotrexate and greater cytotoxicity of tumor cells compared with simply administering the drug alone. ‘‘This therapeutic approach needs to be further explored,’’ Tyagi told Materials Today, ‘‘but we believe our delivery system will open new avenues and come up with innovations in brain cancer and its treatment.’’ Cordelia Sealy
Diamonds are a neuron’s best friend Diamonds may – or may not – be a girls’ best friend, but they are proving to be the ideal material for devices interfacing with the brain. Over the last decade, the chemical non-reactivity, stability, and lack of immunogenicity of diamond have marked it out as an ideal candidate for neural implants. Now researchers from the UK and Ireland have confirmed diamond’s credentials and devised a protocol for culturing neurons from stem cells on its surface [P.A. Nistor, et al. Biomaterials 61 (2015) 139]. ‘‘Until now, the medical community have not really considered using diamond for implants,’’ explains Paul W. May of the University of Bristol, who worked with colleagues at Trinity College, Dublin and the University of Exeter on the study. ‘‘However, the last two decades has seen the emergence of chemical vapor deposition (CVD). . . so diamond can now be considered an inexpensive engineering material.’’ Although diamond’s extreme stiffness rules out use as an implant in moving 420
Human neurons growing on a boron-doped diamond substrate stained to make the various parts of the neurons visible. Blue shows the cell nuclei, green shows tubulin (i.e. where the dendrites are), and red indicates glial fibrillary acidic protein (GFAP). Scale bar = 25 mm.
parts of the body, its bio-inertness and ability to conduct electrically when doped are attractive for brain and nerve
implants. Diamond is so bio-inert that the body does not recognize it is a foreign body, explains May, minimizing rejection and significantly reducing the build up of scar tissue around the implant. But what, the researchers wondered, happens when diamond is doped with boron to make it conductive? The team compared growth and survival of human neurons on undoped and boron-doped diamond and found no difference. ‘‘Boron in its normal state is considered toxic, but a crucial finding from our studies is that when trapped inside diamond it does not affect or kill any cells attached to the surface,’’ May told Materials Today. ‘‘Borondoped diamond is safe and nontoxic.’’ The researchers found that surface microstructure does make a difference to neuron growth and proliferation, however. While all diamond surfaces can potentially sustain long-term survival of human neuron and glial cells, surfaces with large crystals support few cells. Polycrystalline surfaces, by con-
tiny fragments behind. The new dissolvable patch eliminates this risk, as the microneedles are designed to dissolve in the skin.
Materials Today Volume 18, Number 8 October 2015
‘‘We have shown that the patch is safe and that it works well. Since it is also painless and very easy for non-trained people to use, we think it could bring
about a major change in the way we administer vaccines globally,’’ said Professor Nakagawa. Lucy Goodchild
Nanoscale drug carriers bypass blood–brain barrier
NEWS
Treating brain cancers is difficult because of the blood–brain barrier (BBB), which protects the body’s most vital organ. This security system of blood vessels lined with tightly packed endothelial cells lets in essential nutrients, but keeps out foreign substances so effectively that the delivery of life-saving drugs is also blocked. But in a step towards overcoming the BBB, researchers from India and the USA have engineered the surface of nanosized polymeric drug carriers to bind onto cancer cells [Jain, et al., Acta Biomater. (2015), doi:10.1016/ j.actbio.2015.06.027]. While the BBB is very good at blocking large molecules from entering, much smaller and/or fat-soluble molecules are able to slip past the endothelial cell barrier. So the researchers, led by Vandana Soni at Dr Hari Singh Gour University in India and Thomas J. Webster at Northeastern University, designed a nanocarrier system based on poly (D,L-lactide-co-glycolide) (PGLA) nanoparticles coated with a water-soluble surfac-
tant, polysorbate 80, and loaded with a protein (transferrin, Tf) that binds onto cancer cells and an anticancer drug (methotrexate, Mtx). The other authors of the study are Neeraj K. Garg, Rajeev K. Tyagi, Atul Jain, Ashay Jain, Bhupinder Singh, and O.P. Katare. ‘‘To be an efficient delivery vehicle, polymeric nanocarriers must encompass multifunctional properties like biocompatibility, bio-distribution, non-toxicity, and be capable of overcoming biological barriers,’’ explains Tyagi. ‘‘[Our] nanoparticles are nanometric in range (200 nm) and lipophilic in nature, which helps them cross the BBB.’’ The protective polysorbate 80 coating helps the nanoparticles cross the BBB, while the addition of transferrin enables them to targets tumor cells and penetrate the cell membrane. Once in the brain, the combination also regulates the release of methotrexate, leading to long-lasting drug delivery. Importantly, the better targeting
of cancer cells reduces the dose of methotrexate received by other healthy cells. ‘‘Selective and targeted delivery of cytotoxic drugs towards malignant tumors might overcome loopholes with the existing therapeutic system when talking about brain cancer,’’ says Tyagi. ‘‘Polysorbate-80 coated polymeric nanoparticles conjugated with Tf-Mtx not only provide specific targeting across the BBB, but also suppress possible adverse effects in peripheral normal tissues/cells.’’ In tests with rats, the surface-engineered nanoparticles led to higher cellular uptake of the methotrexate and greater cytotoxicity of tumor cells compared with simply administering the drug alone. ‘‘This therapeutic approach needs to be further explored,’’ Tyagi told Materials Today, ‘‘but we believe our delivery system will open new avenues and come up with innovations in brain cancer and its treatment.’’ Cordelia Sealy
Diamonds are a neuron’s best friend Diamonds may – or may not – be a girls’ best friend, but they are proving to be the ideal material for devices interfacing with the brain. Over the last decade, the chemical non-reactivity, stability, and lack of immunogenicity of diamond have marked it out as an ideal candidate for neural implants. Now researchers from the UK and Ireland have confirmed diamond’s credentials and devised a protocol for culturing neurons from stem cells on its surface [P.A. Nistor, et al. Biomaterials 61 (2015) 139]. ‘‘Until now, the medical community have not really considered using diamond for implants,’’ explains Paul W. May of the University of Bristol, who worked with colleagues at Trinity College, Dublin and the University of Exeter on the study. ‘‘However, the last two decades has seen the emergence of chemical vapor deposition (CVD). . . so diamond can now be considered an inexpensive engineering material.’’ Although diamond’s extreme stiffness rules out use as an implant in moving 420
Human neurons growing on a boron-doped diamond substrate stained to make the various parts of the neurons visible. Blue shows the cell nuclei, green shows tubulin (i.e. where the dendrites are), and red indicates glial fibrillary acidic protein (GFAP). Scale bar = 25 mm.
parts of the body, its bio-inertness and ability to conduct electrically when doped are attractive for brain and nerve
implants. Diamond is so bio-inert that the body does not recognize it is a foreign body, explains May, minimizing rejection and significantly reducing the build up of scar tissue around the implant. But what, the researchers wondered, happens when diamond is doped with boron to make it conductive? The team compared growth and survival of human neurons on undoped and boron-doped diamond and found no difference. ‘‘Boron in its normal state is considered toxic, but a crucial finding from our studies is that when trapped inside diamond it does not affect or kill any cells attached to the surface,’’ May told Materials Today. ‘‘Borondoped diamond is safe and nontoxic.’’ The researchers found that surface microstructure does make a difference to neuron growth and proliferation, however. While all diamond surfaces can potentially sustain long-term survival of human neuron and glial cells, surfaces with large crystals support few cells. Polycrystalline surfaces, by con-