Stories about: drug delivery

Intravenous oxygen delivery edges toward the clinic

intravenous-oxygen-delivery
Engineered microparticles that deliver oxygen straight to the bloodstream in emergency situations

Sudden oxygen deprivation can happen for many reasons, from choking to aspiration to cardiac arrest. In these emergency situations, rapid oxygen delivery can mean the difference between life and death. But what if the person cannot breathe?

In the summer of 2012, John Kheir, MD, of the Heart Center at Boston Children’s Hospital, published a study in Science Translational Medicine describing an alternative oxygen delivery system. Kheir used tiny, gas-filled microparticles with a thin outer layer of lipids (fatty molecules) that combined to form a liquid foam-like substance. Injected into the bloodstream, the particles rapidly dissolved and delivered oxygen gas directly to the red blood cells in animal models. But the bubbles were very unstable and not suitable for clinical use.

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Harnessing MRI to steer drugs to hard-to-reach targets

drug delivery propelled by MRI

Once a drug is injected systemically, can you steer it to where you want it under MRI guidance? Pierre Dupont, PhD, and colleagues saw this as an engineering problem. Solving it could enable concentrated drug delivery to, say, a deep tumor in the lungs while simultaneously taking images.

Labeling drugs with magnetized particles is the first step, allowing the MRI scanner’s magnetic pulses to propel them. The next step is to be able to actively steer the particles through a series of branching vessels to a desired location. But getting a scanner to both image and propel particles forcefully enough to overcome the force of the blood flow is easier said than done.

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Topical antibiotics for otitis media: A one-squirt cure?

otitis media transtympanic gel
A single-application gel could revolutionize treatment of ear infections, reducing side effects and drug resistance. (Click to play animation.) Credit:Kohane group

Otitis media, or middle-ear infection, affects 95 percent of children and is the number one reason for antibiotic prescriptions in pediatrics. Typically, antibiotic treatment involves 7 to 10 days of oral medication — several times a day — a formidable task for parents of little kids.

“Force-feeding antibiotics to a toddler by mouth is like a full-contact martial art,” says Daniel Kohane, MD, PhD, a pediatrician and director of the Laboratory for Biomaterials and Drug Delivery at Boston Children’s Hospital.

A single-application bioengineered gel could be the answer to parents’ and pediatricians’ prayers. Described in a paper published today in Science Translational Medicine, the gel would provide an entire course of therapy through a single squirt into the ear canal. It was developed by Kohane’s team in collaboration with investigators at Boston Medical Center and Massachusetts Eye and Ear.

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Drug-eluting contact lens offers hope in glaucoma

Daniel Kohane drug-eluting contact lens
Contact lenses ringed with a drug-bearing polymer film provided gradual, sustained drug release in this preclinical study, potentially offering an alternative to eye drops.

Daily medicated eye drops are the first line of treatment for glaucoma, the leading cause of irreversible blindness. The drops relieve pressure in the eye, a significant risk factor for glaucoma. But they’re not ideal: their delivery is imprecise, they can cause stinging and burning and patients often struggle to administer them. Adherence is poor: in one study based on insurance claims data, nearly half of patients who had filled a glaucoma prescription stopped topical glaucoma therapy within six months.

Engineered contact lenses dispensing glaucoma medication gradually could vastly improve adherence, helping hang onto their eyesight longer. In a pre-clinical study of glaucoma published online this week in the journal Ophthalmology, slow-release lenses lowered eye pressure at least as well as daily eye drops containing the drug latanoprost — and, in a higher-dose form, possibly more so.

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DIY pain relief with light-activated local nerve blocks

light-activated liposomes
Injected, gold-coated liposomes could release painkillers on demand when heated with NIR light. (Shutterstock)

You’ve just had a root canal or knee surgery — both situations that will likely require some sort of local pain medication. But instead of taking a systemic narcotic with all its side effects, what if you could medicate only the part of your body that hurts, only when needed and only as much as necessary?

That concept is today’s reality in the laboratory of Daniel Kohane, MD, PhD, professor of anesthesia at Harvard Medical School and a senior associate in pediatric critical care at Boston Children’s Hospital.

The Kohane laboratory is developing a patient-triggered drug delivery system — but not a simple time-release mechanism or one tethered to ports or pumps. Instead, around the time of an intervention, pain medication would be injected into the site, or around a nerve leading to that site. Whenever pain relief is needed, the patient triggers release of the drug with a laser-like light-emitting device. “It’s like carrying the pharmacy in your body,” explains Kohane.

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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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