The year in nanotech drug delivery

Here at FierceDrugDelivery, we write often about innovations in nanotechnology as it becomes more and more important in the delivery field. These advances are mostly in the very early stages, but they're still promising as the delivery field moves even further into the nanoscale. Last year's report highlighted some companies that have since made an even bigger impact in biotech as a whole, including the newly public Bind Therapeutics ($BIND) and hot RNAi specialist Alnylam ($ALNY). You'll see familiar names in both the industry and the academic realm in this year's report, among others that have offered important developments to the arena.

Nanotech is still a very new field in medicine, and this wave of delivery innovations is for the most part a step or two away from becoming a marketable reality. The FDA is, in fact, working on a way to approach regulation of nanotechnology and manage the possible risks associated with its use, some of which may still be unknown. This is the case with any new technology, of course, but the FDA still needs to clarify its stance on the matter before these can become de facto products. For now, with a few notable exceptions, advances in nanotech remain largely in preclinical stages.

These innovations represent some of the more interesting published studies across a wide range of delivery methods, from nanoparticles designed to deliver dangerous cancer drugs; structures designed to time the release of a specific dose; studies related to what kind of shape makes the best delivery vehicle; and more. The list by no means includes all the work being done in the field, but it represents a glimpse into what the future of nanotechnology might offer drug delivery in coming years.

Scroll down to see the complete list or use the following links to reach specific items. Thank you for reading FierceDrugDelivery, and here's to another year of important innovations in nanotechnology. -- Michael Gibney (email | Twitter)

1. Inhaled nanoparticles for lung cancer

2. Shape matters: Nanorods enhance blood vessel delivery

3. Drug eruption: 'Nanovolcanoes' deliver precise doses

4. Nanoparticle 'traffic jams' enhance RNAi delivery

5. One-two-three punch for cancer treatment

6. Heated nanoparticles enhance chemo efficacy

7. Sperm-driven microrobots offer delivery mobility

8. 'DNA origami' shapes vehicles to be used for delivery

9. Nanodiamond contact lens releases glaucoma drugs slowly

10. Carrying RNAi to the liver using nature-inspired vehicles

FierceDrugDelivery Nanotech Roundup

1. Inhaled nanoparticles for lung cancer

Delivery: Spherical nanoparticles coated with siRNA
Drug: Chemotherapy for lung cancer

The scoop: At Oregon State University, Rutgers University and the Cancer Institute of New Jersey, researchers developed nanoparticles designed to carry chemotherapy to the lungs, delivering them locally to treat forms of lung cancer. According to the study published in the Journal of Controlled Release, the inhaled nanoparticles hold the drug on the inside and come with a coating of small interfering RNA (siRNA) to silence genes, making the cancer cells more vulnerable to the treatment. In the preclinical study, 83% of the drug reached its target in the lungs. Using the traditional approach of intravenous chemotherapy, only 23% reached the lungs, having accumulated in other organs with detrimental effects.

Quotable: "A drug delivery system that can be inhaled is a much more efficient approach, targeting just the cancer cells as much as possible," said co-author Oleh Taratula in a statement. "Other chemotherapeutic approaches only tend to suppress tumors, but this system appears to eliminate it."

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Inhalable nanoparticles to be used as a lung cancer treatment--Courtesy of Oregon State University

 

 

2. Shape matters: Nanorods enhance blood vessel delivery

Delivery: Long, thin particles deliver better to blood vessels in the lungs and brain
Drug: Various

The scoop: The shapes of nanomedicines are crucial to how they act in both the carrying of drugs and their dispersal in the body: Different shapes are suited for different functions. And this past year, researchers have made some headway in finding which shapes work best under which conditions. At the University of California, Santa Barbara, and the Sanford-Burnham Medical Research Institute, researchers found that nanorods--long and thin as opposed to spherical--perform best as delivery vehicles to bring drugs to blood vessels in the lungs and brain.

The stretched-out nanoparticles were found to have a greater surface area to bind to cells in the blood vessels, according to the scientists' study published in the Proceedings of the National Academy of Sciences. The rods are essentially "stickier" and adhere to the cells much more readily. This specificity could help maximize treatments in these areas.

Quotable: "While nanoparticle shape has been shown to impact cellular uptake, the latest study shows that specific tissues can be targeted by controlling the shape of nanoparticles," Samir Mitragotri of UCSB said in a statement at the time of publication. "Keeping the material, volume and targeting antibody the same, a simple change in the shape of the nanoparticle enhances its ability to target specific tissues."

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A study shows that nanorods have a greater effect on diseases such as cancer.--Courtesy of Peter Allen, UCSB

3. Drug eruption: 'Nanovolcanoes' deliver precise doses

Delivery: Tiny, hollow mounds with a sized hole on top for timing doses
Drug: Various

The scoop: Many possible words can come after the "nano" prefix, but "volcano" is one that lends a bit of intrigue. These tiny cones, designed by researchers at North Carolina State University to hold drugs in a hollow section and deliver them through a spout, do resemble their geological counterparts. But these nanovolcanoes, as published in the journal ACS Nano, are uniquely tailored to deliver a precise amount of drug over a specific period of time.

The scientists baked these nanoparticles by placing spherical particles on a thin film and shining them with an ultraviolet light that left them mounted to the surface and, depending on the wavelength of the light, with a hole on top of a controlled size. With funding from NASA and the National Science Foundation, the researchers are now looking into what that control implies in a delivery context.

Quotable: "The materials used in this process are relatively inexpensive, and the process can be easily scaled up," co-author Chih-Hao Chang said in a statement. "In addition, we can produce the nanovolcanoes in a uniformly patterned array, which may also be useful for controlling drug delivery."

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A nanovolcano capable of storing and releasing drugs--Courtesy of Chih-Hao Chang

4. Nanoparticle 'traffic jams' enhance RNAi delivery

Delivery: Loading RNA strands into nanoparticles that remain in a cell for an extended period of time
Drug: Gene-silencing RNAi

The scoop: RNAi drugs are a unique challenge in delivery. The Nobel Prize-winning discovery from almost a decade ago is still hampered by the difficulty of delivering genetic material in a way that doesn't harm the structure but still performs its function. Researchers at MIT, including professor and entrepreneur Robert Langer, have found a way to package strands of RNA into nanoparticles that are designed to remain in a cell for longer than normal. Thus, the genetic material has a longer amount of time to reach the cells' genes and silence the disease-causing sequences there.

In a Nature Biotechnology-published study, the scientists called this particular effect a nanoparticle "traffic jam." RNAi specialist Alnylam Pharmaceuticals ($ALNY) and the National Heart, Lung, and Blood Institute contributed to the study.

Quotable: "We've been able to develop nanoparticles that can deliver payloads into cells, but we didn't really understand how they do it," MIT professor Daniel Anderson said in a statement. "Once you know how it works, there's potential that you can tinker with the system and make it work better."

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siRNA strands in nanoparticles transported in an endocytic vesicle--Courtesy of MIT

5. One-two-three punch for cancer treatment

Delivery: Platinum-based radiotherapy with targeted approach
Drug: Various

The scoop: Researchers at Brigham and Women's Hospital and the Dana-Farber Cancer Institute have developed a platinum-based radiotherapy system that uses a staged process to target and kill cancer cells specifically. Along with team members from Harvard, UMass and Northeastern University, the scientists created a nanoparticle implant designed to place markers in cancer cells to allow for the delivery of platinum-based drugs that are activated by radiotherapy. The tagging-delivery-activation approach, called RAID, allows for a targeted three-step cancer treatment that could help reduce side effects while delivering a lethal drug dose to tumors.

Quotable: "The promising result of using approved platinum-based nanoparticles combined with experimental results of the past two years convince us that our new RAID approach to cancer provides a number of possibilities for customizing and significantly improving radiotherapy," lead author Wilfred Ngwa said in a statement.

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An electron image of the smart implant loaded with stealth nanoparticles--Courtesy of Northeastern University

6. Heated nanoparticles enhance chemo efficacy

Delivery: Heated nanoparticles to enhance drug function
Drug: Doxorubicin

The scoop: Researchers at Oregon State University published a study in the International Journal of Pharmaceutics demonstrating that a combination of mild heat and nanoparticle-delivered chemotherapy can have a staggering effect on ovarian cancer cells that have become resistant to cancer drugs. The delivery of the chemotherapeutic compound doxorubicin using iron oxide nanoparticles, which were designed to heat up once they are in the cancer cells, killed up to 95% of the cancer cells in early lab tests. The nanoparticles target the cancer cells specifically with a peptide and are then heated with a magnetic field.

Quotable: "I'm very excited about this delivery system," OSU researcher Oleh Taratula said in a statement. "Cancer is always difficult to treat, and this should allow us to use lower levels of the toxic chemotherapeutic drugs, minimize side effects and the development of drug resistance, and still improve the efficacy of the treatment. We're not trying to kill the cell with heat, but using it to improve the function of the drug."

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Heated iron oxide nanoparticles release cancer drugs and kill ovarian cancer cells.--Courtesy of Oregon State University

7. Sperm-driven microrobots offer delivery mobility

Delivery: Microrobots use sperm flagella to move forward
Drug: Various

The scoop: Mobility is often a challenge in drug delivery. Getting a drug moving to where it is needed to deliver its payload, at such a small scale, can be difficult. Now researchers at the German Institute for Integrative Nanosciences have developed a microrobot that uses the flagellum of a live sperm cell to propel a drug-carrying vehicle to a desired target. The robot is polar, too, so it can be steered using a magnetic field.

To make the biohybrid microrobot, the team built tiny, hollow, cone-shaped tubes that, when mixed with bull sperm, captured the live cells with their flagella free to move the entire compound forward.

Quotable: "The combination of a biological power source and a microdevice is a compelling approach to the development of new microrobotic devices with fascinating future applications," lead author Oliver Schmidt and his team wrote in the abstract in the journal Advanced Materials.

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Sperm-driven microrobots could deliver drugs.--Courtesy of the Institute for Integrative Nanosciences

8. 'DNA origami' shapes vehicles to be used for delivery

Delivery: Structures capable of carrying drugs with high specificity
Drug: Various

The scoop: Molding shapes out of nanostructures is an important process in drug delivery, as these shapes can determine the outcome of a treatment depending on where or how a drug should be released. Using a method called "DNA origami," researchers at Harvard's Wyss Institute used DNA to create cages that could someday be used to deliver drugs, as well as act as imaging agents, according to a study published by Peng Yin and colleagues in the journal Science.

With small tripod structures made of DNA, the scientists discovered that cages of many different polyhedral shapes could be constructed when manipulated to do so. The self-assembling parts are designed to attract one another in a predetermined fashion, ultimately coming together to form cages that are 60 times larger than the DNA building blocks and 400 times larger than the individual DNA bricks. And because they are made of DNA, they can also be modified to include proteins for targeted delivery or gold nanoparticles for imaging.

Quotable: "Bioengineers interested in advancing the field of nanotechnology need to devise manufacturing methods that build sturdy components in a highly robust manner, and develop self-assembly methods that enable formation of nanoscale devices with defined structures and functions," Wyss Institute Director Don Ingber said in a statement. "Peng's DNA cages and his methods for visualizing the process in solution represent major advances along this path."

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DNA polyhedrons made using the process of DNA origami and imaged using DNA-PAINT--Courtesy of Harvard

9. Nanodiamond contact lens releases glaucoma drugs slowly

Delivery: Contact lens with nanodiamond gel
Drug: Glaucoma drug timolol maleate

The scoop: The drug-eluting contact lens is not entirely new, but researchers at UCLA have developed one that could solve many of the issues involved with the delivery devices. Using a nanodiamond gel, the scientists created a lens that releases the glaucoma drug timolol maleate when it is exposed to an enzyme in tears called lysozyme. The enzyme triggers the release of the drug while allowing the eye to retain the drug instead of letting it leak, according to the study, published in the journal ACS Nano.

The nanodiamonds are combined with the naturally occurring polymer chitosan, which breaks down in the presence of tears to release the drug slowly in the eye. And to mass-produce such lenses down the road, nanodiamonds are actually not hard to come by, as they are a byproduct of mining and relatively inexpensive at the nanoscale.

Quotable: "The reason we use nanodiamonds is they form uniform particles at about 5 nanometers in diameter with a unique faceted architecture resembling a truncated octahedron, like a soccer ball with sharp faces," lead author Dean Ho told FierceDrugDelivery at the time. "These surfaces have a unique charge that binds many types of drugs and releases them slowly instead of all at once."

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Nanodiamond-embedded contact lens for sustained drug delivery--Courtesy of UCLA

10. Carrying RNAi to the liver using nature-inspired vehicles

Delivery: Molecules mimicking cholesterol vehicles to deliver genetic material
Drug: RNAi drugs

The scoop: Alnylam ($ALNY) is known for its work on RNAi drugs, bringing them ever closer to approval, as well as its $700 million partnership early this year with Sanofi ($SNY). On the preclinical side, though, Alnylam is also making headway on delivery platforms for RNA. Working with MIT's Robert Langer, the industry-academic team published a study demonstrating the use of nanoparticles inspired by natural vehicles the body uses to transport cholesterol to deliver the genetic material.

In a mouse study published in the Proceedings of the National Academy of Sciences, the researchers demonstrated that the RNA transported in these nanoparticles silenced a blood-clotting protein in the liver up to 5 times more efficiently than when delivered by other RNA vehicles. This type of platform could also help in cancer treatment.

Quotable: "What we're excited about is how it only takes a very small amount of RNA to cause a gene knockdown in the whole liver," lead author Daniel Anderson of MIT said in a statement. "The effect is specific to the liver--we get no effect in other tissues where you don't want it."

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MIT's nanoparticles (red) delivering RNA (green) to cells (blue)--Courtesy of MIT

 

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