Using injectable self-assembled nanomaterials for sustained delivery of drugs

Because they can be programmed to travel the body and selectively target cancer and other sites of disease, nanometer-scale vehicles called nanocarriers can deliver higher concentrations of drugs to bombard specific areas of the body while minimizing systemic side effects. Nanocarriers can also deliver drugs and diagnostic agents that are typically not soluble in water or blood as well as significantly decrease the effective dosage.

Although this method might seem ideal for treating diseases, nanocarriers are not without their challenges.

"Controlled, sustained delivery is advantageous for treating many chronic disorders, but this is difficult to achieve with nanomaterials without inducing undesirable local inflammation," said Northwestern University's Evan Scott. "Instead, nanomaterials are typically administered as multiple separate injections or as a transfusion that can take longer than an hour. It would be great if physicians could give one injection, which continuously released nanomaterials over a controlled period of time."

Now Scott, an assistant professor of biomedical engineering in Northwestern's McCormick School of Engineering, has developed a new mechanism that makes that controlled, sustained delivery possible.

Scott's team designed a nanocarrier formulation that - after quickly forming into a gel inside the body at the site of injection - can continuously release nanoscale drug-loaded vehicles for months. The gel itself re-assembles into the nanocarriers, so after all of the drug has been delivered, no residual material is left to induce inflammation or fibrous tissue formation. This system could, for example, enable single-administration vaccines that do not require boosters as well as a new way to deliver chemotherapy, hormone therapy, or drugs that facilitate wound healing.

Supported by the National Science Foundation and National Institutes of Health, the research was published online today, February 12 in the journal Nature Communications. Nicholas Karabin, a graduate student in Scott's laboratory, was the paper's first author. Northwestern Engineering's Kenneth Shull, professor of materials science and engineering, also contributed to the work. A member of Northwestern's Simpson Querrey Institute for BioNanotechnology and Chemistry of Life Processes Institute, Scott was corresponding author and led the nanoparticle development and in vivo validation.

Currently, the most common sustained nanocarrier delivery systems hold nanomaterials within polymer matrices. These networks are implanted into the body, where they slowly release the trapped drug carriers over a period of time. The problem lies after the delivery is complete: the networks remain inside the body, often eliciting a foreign-body response. The leftover network can cause discomfort and chronic inflammation in the patient.

To bypass this issue, Scott developed a nanocarrier using self-assembled, filament-shaped nanomaterials, which are loaded with a drug or imaging agent. When crosslinked together, the filaments form a hydrogel network that is similar to structural tissue in the human body. After the filaments are injected into the body, the resulting hydrogel network functions as a drug depot that slowly degrades by breaking down into spherical nanomaterials called micelles, which are programmed to travel to specific targets. Because the network morphs into the drug-delivery system, nothing is less behind to cause inflammation.

"All of the material holds the drug and then delivers the drug," Scott explained. "It degrades in a controlled fashion, resulting in nanomaterials that are of equal shape and size. If we load a drug into the filaments, the micelles take the drug and leave with it."

After testing the system both in vitro and in vivo in an animal model, Scott's team demonstrated they could administer a subcutaneous injection that slowly delivered nanomaterials to cells in lymph nodes for over a month in a controlled fashion.

Scott said the system can be used for other nanostructures in addition to micelles. For example, the system could include vesicle-shaped nanoparticles, such as liposomes or polyersomes, that have drugs, proteins, or antibodies trapped inside. Different vesicles could carry different drugs and release them at different rates once inside the body.

"Next we are looking for ways to tailor the system to the needs of specific diseases and therapies," Scott said. "We're currently working to find ways to deliver chemotherapeutics and vaccines. Chemotherapy usually requires the delivery of multiple toxic drugs at high concentrations, and we could deliver all of these drugs in one injection at much lower dosages. For immunization, these injectable hydrogels could be administered like standard vaccines, but stimulate specific cells of the immune system for longer, controlled periods of time and potentially avoid the need for boosters."

Nicholas B Karabin, Sean Allen, Ha-Kyung Kwon, Sharan Bobbala, Emre Firlar, Tolou Shokuhfar, Kenneth R Shull, Evan A Scott.
Sustained micellar delivery via inducible transitions in nanostructure morphology.
Nature Communicationsvolume 9, Article number: 624 (2018). doi: 10.1038/s41467-018-03001-9.

Most Popular Now

Forxiga receives positive EU CHMP opinion for the …

The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has recommended a new indication for the marketing authorisation of Forxi...

US FDA grants Breakthrough Therapy Designation for…

AstraZeneca and its global biologics research and development arm, MedImmune, today announced that the US Food and Drug Administration (FDA) has granted Breakthrough Ther...

New pill can deliver insulin

An MIT-led research team has developed a drug capsule that could be used to deliver oral doses of insulin, potentially replacing the injections that people with type 2 di...

Merck to expand US biopharmaceutical R&D facil…

Merck, a leading science and technology company, today announced a $70 million investment to expand its state of the art research and development (R&D) facility in Biller...

Pfizer receives positive CHMP opinion for Vizimpro…

Pfizer today announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion recommending V...

Cannabinoid compounds may inhibit growth of colon …

Medical marijuana has gained attention in recent years for its potential to relieve pain and short-term anxiety and depression. Now, Penn State College of Medicine resear...

Merck Granted U.S. Patent for novel combination of…

Merck, a leading science and technology company, today announced that it has been granted Patent No. US 10,193,695 by the United States Patent and Trademark Office (USPTO...

Simple drug combination creates new neurons from n…

A simple drug cocktail that converts cells neighboring damaged neurons into functional new neurons could potentially be used to treat stroke, Alzheimer's disease, and bra...

The Union for International Cancer Control and Pfi…

In conjunction with World Cancer Day, the Union for International Cancer Control (UICC) and Pfizer Inc. announce the third round of the Seeding Progress And Resources for...

Pfizer and Lilly announce top-line results from se…

Pfizer Inc. (NYSE:PFE) and Eli Lilly and Company (NYSE:LLY) today announced positive top-line results from a Phase 3 study evaluating tanezumab 2.5 mg or 5 mg in patients...

Merck and Tencent announce collaboration on intell…

Merck, a leading science and technology company, signed a strategic collaboration agreement with Tencent, a leading provider of Internet value added services. The collabo...

New insight into cell receptors opens the way for …

New research on how cancer mutations influence a certain type of receptor on the cell membrane opens the way for the development of tailored drugs for certain cancers, su...