Nanodiamonds deliver insulin for wound healing

Jul 27, 2009

(PhysOrg.com) -- Bacterial infection is a major health threat to patients with severe burns and other kinds of serious wounds such as traumatic bone fractures. Recent studies have identified an important new weapon for fighting infection and healing wounds: insulin.

Now, using tiny nanodiamonds, researchers at Northwestern University have demonstrated an innovative method for delivering and releasing the curative hormone at a specific location over a period of time. The nanodiamond-insulin clusters hold promise for applications and could be integrated into gels, ointments, bandages or suture materials.

Localized release of a therapeutic is a major challenge in biomedicine. The Northwestern method takes advantage of a condition typically found at a wound site -- skin pH levels can reach very basic levels during the repair and healing process. The researchers found that the insulin, bound firmly to the tiny carbon-based nanodiamonds, is released when it encounters basic pH levels, similar to those commonly observed in bacterially infected . These basic pH levels are significantly greater than the physiological pH level of 7.4.

The results of the study were published online July 26 by the journal Biomaterials.

"This study introduces the concept of nanodiamond-mediated release of therapeutic proteins," said Dean Ho, assistant professor of biomedical engineering and mechanical engineering at the McCormick School of Engineering and Applied Science. Ho led the research. "It's a tricky problem because proteins, even small ones like insulin, bind so well to the nanodiamonds. But, in this case, the right pH level effectively triggers the release of the insulin."

A substantial amount of insulin can be loaded onto the nanodiamonds, which have a high surface area. The nanodiamond-insulin clusters, by releasing insulin in alkaline wound areas, could accelerate the healing process and decrease the incidence of infection. Ho says this ability to release therapeutics from the nanodiamonds on demand represents an exciting strategy towards enhancing the specificity of wound treatment.

In their studies, Ho and his colleagues showed that the insulin was very tightly bound to the nanodiamonds when in an aqueous solution near the normal physiological pH level. Measurements of insulin function revealed that the protein was virtually inactive when bound to the nanodiamonds -- a beneficial property for preventing excess or unnecessary drug release.

Upon increasing the pH to the basic levels commonly observed in the skin during severe burns, the researchers confirmed the insulin was released from the nanodiamond clusters and retained its function. Exploiting this pH-mediated release mechanism may provide unique advantages for enhanced drug delivery methods.

The researchers also found the insulin slowly and consistently released from the nanodiamond clusters over a period of several days.

Insulin accelerates wound healing by acting as a growth hormone. It encourages skin cells to proliferate and divide, restores blood flow to the wound, suppresses inflammation and fights infection. Earlier investigations have confirmed an increase in alkalinity of wound tissue, due to bacterial colonization, to levels as high as pH 10.5, the pH level that promoted release from the nanodiamonds in the Northwestern study.

Ho's group next will work on integrating the nanodiamond-insulin complexes into a gel and conducting preclinical studies. The researchers also will investigate different areas of medicine in which the nanodiamond-insulin clusters could be used.

Nanodiamonds have many advantages for biomedical applications. The large surface area allows a large amount of therapeutic to be loaded onto the particles. They can be functionalized with nearly any type of therapeutic, including small molecules, proteins and antibodies. They can be suspended easily in water, an important property in biomedicine. The nanodiamonds, each being four to six nanometers in diameter, are minimally invasive to cells, biocompatible and do not cause inflammation, a serious complication. And they are very scalable and can be produced in large quantities in uniform sizes.

By harnessing the unique surface properties of the nanodiamonds, Ho and his colleagues have demonstrated that the nanodiamonds serve as platforms that can successfully bind, deliver and release several classes of therapeutics, which could impact a broad range of medical needs.

Ho's research group also has studied nanodiamonds for applications in cancer therapy. They demonstrated that nanodiamonds are capable of releasing the chemotherapy agent Doxorubicin in a sustained and consistent manner. (Ho is a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.)

In addition to using the nanodiamonds in their particle form, Ho's group has developed devices that harness the slow drug-release capabilities of the nanodiamonds. More recently, his team has shown that nanodiamonds are effective in dispersing insoluble drugs in water, boosting their potential for broader applications in medicine.

More information: The title of the Biomaterials paper is "Nanodiamond-Insulin Complexes as pH-Dependent Protein Delivery Vehicles." www.elsevier.com/wps/find/jour… me/30392/description

Source: Northwestern University (news : web)

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User comments : 7

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Woobie
not rated yet Jul 27, 2009
Cool.
RFC
not rated yet Jul 27, 2009
I'm a little confused. The article talks about Ho working on a gel to utilize his nanodiamond-insulin treatment. So, that should be a topical treatment (I guess it could be oral, but it didn't sound like that). And if it's a topical treatment of insulin to burns, what is the advantage presented by the nanodiamonds? I can understand the advantage if it was an oral or intervenous treatment, for example... just not clear on the advantage in a topical treatment.

Kudos to the research... I just want to understand why this discriminating delivery system is needed for a topical treatment that is fairly discriminating in the first instance (in other words, you topically treat the burns, not other non-wounded tissue).
MongHTanPhD
1 / 5 (1) Jul 27, 2009
RE: The advantage of nanodiamond-insulin in wound healing processes!?

I'm a little confused. The article talks about Ho working on a gel to utilize his nanodiamond-insulin treatment. So, that should be a topical treatment (I guess it could be oral, but it didn't sound like that). And if it's a topical treatment of insulin to burns, what is the advantage presented by the nanodiamonds? I can understand the advantage if it was an oral or intervenous treatment, for example... just not clear on the advantage in a topical treatment.

Kudos to the research... I just want to understand why this discriminating delivery system is needed for a topical treatment that is fairly discriminating in the first instance (in other words, you topically treat the burns, not other non-wounded tissue).


I think you have missed reading these important statements on the wound-healing processes, that are taken advantage of in the nanodiamond-insulin treatment of burns (especially those with infections):

Localized release of a therapeutic is a major challenge in biomedicine. The Northwestern method takes advantage of a condition typically found at a wound site -- skin pH levels can reach very basic levels during the repair and healing process. The researchers found that the insulin, bound firmly to the tiny carbon-based nanodiamonds, is released when it encounters basic pH levels, similar to those commonly observed in bacterially infected wounds. These basic pH levels are significantly greater than the physiological pH level of 7.4.
and
Insulin accelerates wound healing by acting as a growth hormone. It encourages skin cells to proliferate and divide, restores blood flow to the wound, suppresses inflammation and fights infection. Earlier investigations have confirmed an increase in alkalinity of wound tissue, due to bacterial colonization, to levels as high as pH 10.5, the pH level that promoted insulin release from the nanodiamonds in the Northwestern study.


Best wishes, Mong 7/27/9usct4:22p; author "Decoding Scientism" and "Consciousness & the Subconscious" (works in progress since July 2007), "Gods, Genes, Conscience" (2006: http://www.iunive...95379907 ) and "Gods, Genes, Conscience: Global Dialogues Now" (blogging avidly since 2006: http://www2.blogg...50569778 ).
RFC
not rated yet Jul 28, 2009
Mong - I read the article. I get the whole pH idea. That was not my question. My question pertained to why nanoparticles present an advantage in a topical application. Nanoparticles are (here) a delivery system. pH acts as a trigger for insulin to be release from the delivery system (i.e. "please drop here"). However, topicals inherently release on the topic site, so that's where my question comes from.

antialias
5 / 5 (1) Jul 28, 2009
Maybe the advantage is that the 'reactive agent' is not released where it is not needed (having insulin act on healthy skin may not be a wanted side effect)?

Also the pH-Value does change with the time of the lesion. So using this type of setup the insulin is released over time (whereas a normal gel would release allmost all its agent simultaneously)



Just a hypothesis, though....
RFC
not rated yet Jul 28, 2009
Antialias - "Just a hypothesis"....

But an interesting one! Would be interesting too if a gel was made of a variety of nanodiamonds that released different medicine depending on the pH of the wound. Not sure that's possible, but I could see that being useful in emergency applications in particular.
MongHTanPhD
1 / 5 (1) Jul 28, 2009
RE: The pharmacokinetics of nanodiamond-insulin topicals!?

Mong - I read the article. I get the whole pH idea. That was not my question. My question pertained to why nanoparticles present an advantage in a topical application. Nanoparticles are (here) a delivery system. pH acts as a trigger for insulin to be release from the delivery system (i.e. "please drop here"). However, topicals inherently release on the topic site, so that's where my question comes from.


In the pharmacokinetics of any tropical therapeutics -- the tropicals (without specifically-designed carriers or releasers or pumps) would not be inherently released topically -- they would defuse instantly and be absorbed subcutaneously into the blood system; as one hypothesis accurately queried below:

Maybe the advantage is that the 'reactive agent' is not released where it is not needed (having insulin act on healthy skin may not be a wanted side effect)?

Also the pH-Value does change with the time of the lesion. So using this type of setup the insulin is released over time (whereas a normal gel would release almost all its agent simultaneously).

Just a hypothesis, though....


In the Ho case -- as insulin-coated nanodiamonds would not be absorbed by the skin -- the inert nanoparticles would hold insulin topically, until insulin-release is triggered by the higher pH values of beyond 7.4 (at the burn-wound site) so as to help accelerate the topical wound-healing processes, without incurring any systemic side effects!?

Best wishes, Mong 7/28/9usct3:03p; author "Decoding Scientism" and "Consciousness & the Subconscious" (works in progress since July 2007), "Gods, Genes, Conscience" (2006: http://www.iunive...95379907 ) and "Gods, Genes, Conscience: Global Dialogues Now" (blogging avidly since 2006: http://www2.blogg...50569778 ).