Stories about: drug delivery

Lasers for on-demand local pain relief?

laser drug delivery pain relief
(Juergen Faelchle/Shutterstock)

Consider this scenario: A patient is home recovering from knee surgery to repair an ACL tear. Her pain medications are wearing off, and the surgical cuts are starting to throb. Reaching over to the table she picks up what’s essentially a souped-up laser pointer, points it at the surgical wound and turns it on. Within seconds, the pain starts to fade.

This picture isn’t as far-fetched as you might think. In a pair of simultaneous papers, Boston Children’s Hospital’s Daniel Kohane, MD, PhD, and his laboratory recently reported their efforts to create not one, but two methods for packaging long-lasting local anesthetics in microspheres that could be injected in advance by a surgeon or anesthesiologist and that would release the drugs when zapped with a laser. Both methods have one goal in common: to provide patients with durable, localized and personalized control of surgical, traumatic or chronic pain with minimal side effects.

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Realities of relativity nudge researcher to alternate career plan

From a series profiling researchers and innovators at Boston Children’s Hospital

He’s a big thinker focused on harnessing the hyper-small. Daniel Kohane, MD, PhD, is a leading drug delivery and biomaterials researcher, leveraging nanoparticle technology and other new vehicles to make medications safer and more effective.

It’s not quite what he had in mind as a child. He dreamed of studying life forms in remote galaxies.

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But when he became aware of the constraints of relativity, he re-focused his ambitions, ultimately concentrating on innovations in drug delivery. Here’s what he told us.

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DNA paired with light could help guide drugs to their targets

UV light-activated aptamers Dan Kohane drug delivery
Short snippets of DNA called aptamers (red) readily get into cancer cells (green and blue) on their own (left panel). They can't penetrate cells when stuck to an oligonucleotide (center), but regain the ability when the oligonucleotide's bonds are broken by UV light (right). (Images courtesy Lele Li, PhD.)

You have a drug. You know what you want it to do and where in the body you need it to go. But when you inject it into a patient, how can you make sure your drug does what you want, where you want, when you want it to?

Daniel Kohane, MD, PhD, who runs the Laboratory of Biomaterials and Drug Delivery at Boston Children’s Hospital, has one potential solution. In the Proceedings of the National Academy of Sciences, Kohane; postdoctoral fellows LeLe Li, PhD, and Rong Tong, PhD; and Robert Langer, PhD, of Massachusetts Institute of Technology, describe a drug- targeting system that’s based on a combination of ultraviolet (UV) light and short, single strands of DNA called aptamers.

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Stopping blindness: The drug-eluting contact lens

drug-eluting contact lens
(John Earle Photography)

Growing up, my grandmother’s eyes were always a problem. For years, she was losing her central vision to glaucoma, and numerous surgeries and treatments did not seem to help. Later in life, she could not see my face but could always tell who I was when I was close.

Glaucoma is the leading cause of irreversible blindness worldwide. While FDA-approved medications such as latanoprost can prevent vision loss by reducing pressure in the eye, their beneficial effects are limited by poor patient compliance: At six months of treatment, compliance is estimated to be little more than 50 percent.

Why? First, the medications are typically delivered as eye drops, and the drops themselves can cause stinging and burning. The drops also contain preservatives that can cause ocular surface disease.

Perhaps most importantly, latanoprost and other glaucoma drugs halt the disease’s progression but do not reverse it. Taking the drugs does not provide positive feedback that will motivate patients, such as relieving pain.

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Adventures in gene therapy: Getting our own blood vessels to make drugs

Bioengineered blood vessels
A bioengineered network of blood vessels
Juan Melero-Martin, PhD, runs a cell biology and bioengineering lab in the department of Cardiac Surgery at Boston Children’s Hospital. In May, he received an Early Career Investigator Award from Bayer HealthCare, part of the prestigious Bayer Hemophilia Award.

In 1982, insulin became the first FDA-approved protein drug created through recombinant DNA technology. It was made by inserting the human insulin gene into a bacterial cell’s DNA, multiplying the bacteria and capturing and purifying the human insulin in bioreactors.

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The light side of drug delivery

Daniel Kohane of Boston Children's Hospital is developing drug delivery technologies that rely on nanoparticles and the spectrum of light.Getting drugs where they need to be, and at the right time, can be more challenging than you think. Tumors, for example, tend to have blood vessels that are tighter and twistier than normal ones, making it hard for drugs to penetrate them. Despite decades of research on antibodies, peptides and other guidance methods, drug makers struggle to target drugs to specific tissues or cell types.

And even once a drug arrives at the right place, the ability to fine-tune the dose so that the drug is released at the right time and in the right amount remains an elusive goal.

What’s needed is some kind of trigger, a stimulus that a clinician can turn on and off to guide when a drug is available and where it goes to make sure it does its job with the fewest side effects.

Daniel Kohane, MD, PhD, a critical care specialist and director of the Laboratory for Biomaterials and Drug Delivery at Boston Children’s Hospital, thinks he’s hit upon a promising trigger, one that’s all around us: light.

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Biogen Idec wins FDA approval for long-lasting hemophilia drug based on Boston Children’s technology

Alprolix FDA approval recombinant factor IX rFIXFc hemophilia B coagulation
(Courtesy Biogen Idec)
A few weeks ago Vector brought you the backstory of how a clotting factor for hemophilia was made to last longer in the blood, allowing injections to be pared to once every week or two, rather than two to three per week.

Today we bring more good news: Following a successful Phase III trial, rFIXFc recently received the green light for marketing from the FDA and from Health Canada.

Developed by Biogen Idec under the trade name Alprolix™, rFIXFc—a modified version of clotting factor IX—is the fruition of a technology first envisioned by three researchers—gastroenterologists Wayne Lencer, MD, of Boston Children’s Hospital, and Richard Blumberg, MD, of Brigham and Women’s Hospital, and immunologist Neil Simister, DPhil, of Brandeis University—for large protein drugs. Their idea: to extend the drugs’ half-lives by protecting them from being ground up by cells.

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Five cool medical innovations we saw last week

Last week, Boston Children’s Hospital’s Innovation Acceleration Program hosted a jam-packed Innovators’ Showcase where teams from around the hospital networked, traded ideas and showed off their projects. Here are a few Vector thinks are worth watching.

isotropic diffusion reveals information on axons on DTI1. An imaging ‘biomarker’ after concussion

Thirty percent of people who suffer a mild traumatic brain injury—a.k.a. concussion—have ongoing symptoms that can last months or years. If patients at risk could be identified, they could receive early interventions such as brain cooling and anti-seizure medications. New MRI protocols that can measure free, non-directional diffusion of water, coupled with sophisticated analytics, are achieving unprecedented pictures of what happens inside the brain after injury.

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How can we get clotting factors to last longer in the blood?

Meat grinder protecting protein drugs from being ground up by cells clotting factors
Cells can grind up large protein drugs. A new technology may help those drugs escape and stay in the bloodstream longer.

Getting drugs to stay in the bloodstream longer is a big deal when it comes to treating chronic diseases. You see, a drug’s half-life—the time it takes for half of a given dose to be cleared from the body—determines how long its effect(s) last.

If a drug’s half-life is short—meaning it’s cleared quickly—patients will have to take the drug frequently. Given that someone with a chronic condition could be on the medication for many years—say, patients with severe hemophilia, who endure frequent infusions of clotting factors—a short half-life can translate into high cost. Depending on side effects and how the drug is administered, quality of life may also suffer.

Several years ago, Wayne Lencer, MD, a researcher in Boston Children’s Hospital’s Division of Gastroenterology, Hepatology and Nutrition, and his collaborators Richard Blumberg, MD, at Brigham and Women’s Hospital (BWH) and Neil Simister, DPhil, at Brandeis University came up with a way to make protein-based drugs like clotting factors stay in the circulation longer: by keeping cells from grinding them up.

The first drug based on their work—a form of the factor IX clotting factor—just passed a Phase III clinical trial reported in The New England Journal of Medicine.

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A skin cream for peripheral neuropathy? Small molecule may go a long way

The footpads of diabetic mice (line-D) treated with a cream containing XIB4035 have increased numbers of nerve terminals (shown in green in the lower right panel), whereas mice given a control cream (lower left) do not. The top two panels represent healthy “wild type” mice.
The footpads of diabetic mice given a cream containing XIB4035 (lower right) have new nerve terminals (shown in green), whereas mice given a control cream (lower left) do not. The top two panels represent healthy “wild type” mice.
About half of people with diabetes develop peripheral neuropathy. The most common form, small-fiber neuropathy, generally starts in the feet, causing pain, odd sensations like pricks and “pins and needles,” and—the most worrisome feature—a loss of sensation that can increase the chance of ulcers and infections.

In some cases, that may lead to the need for amputation—as happened with my diabetic great-grandfather whose numbed feet, unbeknownst to him, got too close to the fire.

While there are some treatments to reduce pain, there’s nothing that restores sensation. Nor do any existing treatments address the underlying cause of the neuropathy: the degeneration or dysfunction of the endings of the sensory neurons in the skin.

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