Category: Nanotechnology

Advances in pharmaceutical research- use of nanotechnology as therapeutic platforms for disease management.

8/15/2017

Dr. Shruti Bhat Life Science Industry Thought Leader, brings to you some highlights from current pharma and clinical research news, views and data.

Advances in nanotechnology as therapeutic platforms

New nanoparticles deliver bigger drug payload.
Scientists at Brigham and Women's Hospital and the Harvard-MIT Division of Health Sciences and Technology have developed new nanoparticles from a modified polymer that can more efficiently load up on cancer drugs and deliver them more precisely.

These new nanoparticles inhibit the MARK signaling pathway, which helps prevent the spread of cancer cells and makes tumors more susceptible to chemotherapy.

"Current chemotherapy drugs must be administered in high concentration throughout the body in order to destroy tumor cells, translating to high toxicity and discomfort for the patient, mainly due to the effects on normal cells," co-lead author Rania Harfouche said in a release. By modifying the polymer, researchers "allow for lower drug concentrations to be used, and provide opportunity for more potent treatments with lesser side-effects for the patient."

In a study involving mice, the nanoparticles inhibited tumor growth. And the scientists say that this new approach to cancer therapy could have wide applicability.

Scientist creates 'nanocage' drug delivery system.
Washington University's Younan Xia has been attracting considerable attention for his research work on microcapsules that can precisely deliver a drug payload right where it's needed.

Xia has been making microscopic gold 'nanocages,' tiny particles encased in polymer strands that collapse when exposed to heat. "But the really cool part," says Xia, "and the cool part of nanotechnology generally, is that the tiny gold cages have very different properties than bulk gold." In particular, they respond differently to light.

Using a near infrared light, the scientist can trigger a collapse at any point, leaving the tissue unharmed. Adjusting the light can recalibrate the release rate. And by designing the polymers to latch onto specific disease targets, such as a tumor, Xia believes he can concentrate the drug right where it's needed.

Nanoparticles used to deliver targeted ED drugs.
Nanoparticles "smaller than a grain of pollen" have been engineered to carry minute quantities of therapeutics for erectile dysfunction, effectively delivering the drug directly through the skin in animal models. And the team of researchers at Albert Einstein College of Medicine at Yeshiva
University says that the same approach could be a better alternative to existing drugs while safely working in men who currently are prohibited from taking the tablet meds.

Scientists used rats bred to suffer from erectile dysfunction to test the nanoparticles. "The response time to the nanoparticles was very short, just a few minutes, which is basically what people want in an erectile dysfunction medication," says Dr. Kelvin Davies. "In both rats and humans, it can take 30 minutes to one hour for oral erectile dysfunction medications to take effect."

The oral drugs are associated with a number of side effects, including blurred vision and upset stomachs. Men who have suffered a heart attack, meanwhile, are prevented from getting the ED drugs at all. But the researchers say that a locally applied topical solution was effective without side effects in rodents. ED drugs have been prominent best-sellers and an improved approach could also prove to be highly profitable.

Nanoparticles boost antibacterial treatments.
The University of Liverpool and IOTA NanoSolutions have developed man-made nanoparticles that could increase the effectiveness of antibacterial treatments. Many current drugs are insoluble and need to be administered at higher doses in order to work. However, this increases the chances that bacteria and other organisms will build up a resistance to the drugs. In time, new formulations of medicines must be developed in order to knock out the mutated organisms.

University of Liverpool researchers found that in some instances, the nanoparticles can be used to make insoluble drugs behave like soluble drugs, increasing their effectiveness at lower doses. Scientists are concentrating on applying the nanoparticle technology to antiparasitic drugs that treat malaria.

"Already our technology has shown the potential to improve a range of current medicines and may lead to treatments that prevent drug resistance," said Professor Steve Rannard, from the Department of Chemistry, who is also co-founder and current Chief Scientific Officer of IOTA NanoSolutions. "If our approach can deliver new antimalarial treatments, it may help to prevent millions of deaths per year and improve the lives of hundreds of millions of current malaria sufferers."

Nanoparticles research aids drug development.
Drugs with the ability to dissolve have much stronger efficacy, however many drugs are insoluble. In order to compensate, drugs often need to be administered in higher doses. This increases the possibility of bacteria and other organisms mutating as the high doses make it easier for them to build resistance to the drugs. This leads to treatments becoming obsolete and the need for new medicines to be developed.

Chemists at the University of Liverpool working with IOTA NanoSolutions have now developed a new technology to produce nanoparticles of insoluble drugs that mimic the behaviour and the effectiveness of dissolved drugs.

Nanoparticles are man-made particles manufactured for use in a number of industries including the cosmetic and pharmaceutical industry; they can make materials stronger, lighter and cleaner.

Recent data has shown that in some cases, low concentrations of insoluble drugs in a nanoparticle form can be more active than previously thought, offering the potential to administer drugs in low dosages without reducing the effectiveness of the treatment. The new technology is allowing the scientists to develop new medicines by converting currently available drugs into a nanoparticle form. Antiparastitic drugs to treat malaria are also being developed in collaboration with the Liverpool School of Tropical Medicine.

Professor Steve Rannard, from the Department of Chemistry who is also co-founder and current Chief Scientific Officer of IOTA NanoSolutions, said: "Already our technology has shown the potential to improve a range of current medicines and may lead to treatments that prevent drug resistance. If our approach can deliver new antimalarial treatments, it may help to prevent millions of deaths per year and improve the lives of hundreds of millions of current malaria sufferers."

Nanoparticle program delivers anti-cancer therapy.
A research team at Washington University in St. Louis has combined a nanoparticle platform used in imaging growing blood vessels and combined it with the fungal drug fumagillin to create a new weapon to fight the growth of tumors. Fumagillin has long been known as a potent anti-cancer therapy, but its neurotoxic side effects are too harsh for patients. To circumvent the side effects, the scientists adapted nanoparticles designed to dock on a protein carpeted on endothelial cells clustered on the walls of new blood vessels and loaded them with fumagillin. By targeting the therapy directly at the new blood vessels, the therapy can stop angiogenesis, a key target in oncology research.

"It basically becomes a vehicle to dump off a truckload of cargo," Joseph DeSimone of the University of North Carolina tells MIT Technology Review. "It's sort of like a Trojan horse."

There are a number of research programs underway relying on animal studies to determine the effect of new nanoparticle technologies that can interrupt angiogenesis. First-generation nanoparticle therapies rely on passive delivery methods while this second generation round of research is working on new technology aimed at more precise targeting of disease.

Nanomaterials used to fix neuron damage.
Northwestern University researcher Samuel Stupp has presented the results of a study in which he injected nanomaterials into the severed spinal cords of mice, allowing them to walk again after several weeks of therapy. The nanomaterials he used were designed to self-assemble into nanofibers which repaired damaged neurons. The research offers new insights into the near-term research potential of nanotechnology and offers hope for patients with Alzheimer's and Parkinson's who suffer from severe neuron damage.

"Regenerating bone and cartilage are our first targets," Stupp told the Chicago Tribune. "That would be very important to Baby Boomers who value their quality of life. We are also working with regenerating blood vessels to address damage from heart attacks. (Nanotechnology) will first aid in diagnosing illness, but it also will provide therapies to alleviate or cure."

Nanoparticles offer ovarian cancer treatment approach.
Magnetic nanoparticles have been used to ‘drag' cancer cells out of the bodies of mice. Scientists at Georgia Tech coated the nanoparticles with a targeting molecule that caused them to bond to the cancer cells. And the researchers say the approach could be used to treat metastatic ovarian cancer. During metastasis, the cancer cells drift in the abdominal area, offering a target for the nanoparticles. They believe that a patient's abdominal fluid could be drained, cancer cells filtered out, and then infused back into the abdominal cavity.

"It's possible that the particles may not ever have to go into the patient's body," says John McDonald, the chief scientific officer of the Ovarian Cancer Institute at Georgia Tech. "That would be preferable, because then you don't have to worry about any potential toxicity."

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Intranasal administration route for protein & peptide mucosal delivery.

6/6/2017

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Due to its unique physiology and ready accessibility, the nasal cavity is an attractive delivery site for the systemic administration of therapeutics. The nasal membrane or mucosa lines the nasal cavity and is located posterior to the external nares.

The surface area of the nasal mucosa is relatively large (180 cm2) and has a rich blood supply (40ml/min/100g). Molecules absorbed across the mucosal membranes are transported directly to the blood stream and therefore avoid clearance due to first pass metabolism.

Also, the protease activity in the nasal cavity is greatly diminished relative to the small intestine making enzymatic degradation in the nasal cavity less likely. Relative to chronic parenteral administration, intranasal delivery offers increased patient compliance and in some cases, increased pharmacokinetic control.

Intranasal formulation is a remarkable and easy mode of drug delivery. It is a needle-free, patient-friendly route that does not contribute to biohazardous waste (Wermeling, Miller, & Rudy, N.D.). Pharmacokinetically, the absorption rate is so rapid that it results in a faster onset of action compared with oral and intramuscular administration.

In addition, hepatic first-pass metabolism is avoided (Wermeling et al.,). (The metabolism of an administered dose of a drug by the liver before it reaches systemic circulation is referred to as the first-pass metabolism.)

For many oral drugs, a clinically significant portion of the drug taken is destroyed during first-pass metabolism, requiring a higher oral dose for a given effect (Wynne, Woo, & Olyaei, 2007).

Intranasal administration route for protein & peptide mucosal delivery.Picture

Intranasal drugs can be delivered in a variety of formulations that include powders, drops, topical gels, and sprays. Consideration must be given to normal physiologic processes when using the intranasal route, as the nose is an important defense system for environmental hazards. Any disruption of its normal physiology may leave the patient vulnerable to a variety of complications (Wermeling et al.).

The delivery devices for intranasal medications can be costly, as illustrated by intranasal insulin, and can be a deterrent to patient use. Initially thought to be a desired route compared with subcutaneous insulin, patients found intranasal insulin to be burdensome and costly (R. Talbert, personal communication, February 21, 2008).

Until recently, vitamin B 12 has been available only by intramuscular injection. Calomist (cyanocobalarain) Nasal Spray is now available in a 25-mg/spray form that is used daily in lieu of the monthly injections. This can now be included in the daily routine with less impact of a missed dose.

Medication Adherence

Medication adherence can be problematic with older adults. One of the most basic forms of medication delivery, the pillbox, is continually being updated. An interactive pillbox can be a useful tool in reminding this population about their medication times. Pillboxes are available that can hold as much as a 1-month supply of medications, with separate compartments for as many as four drugs.

After programming, the box will beep at the time a medication is due to be taken, indicate the appropriate compartment, and display the number of pills to take. When the compartment lid is lifted, an audio message instructs the patient on the number of pills to take, along with specific information about how that medication should be taken. The data are gathered and can be transmitted via phone lines to the caregiver to confirm the time at which the medication was taken.

Even patients thought to be compliant accidentally skip doses of medication, a silent problem improved by these devices. Pillboxes with multiple compartments are particularly helpful for older patients when dealing with multiple pill regimens.

The intranasal administration of small organic compound is a well-established mode of delivery. The majority of these drugs however, are intended for local administration to the nasal mucosa rather than systemic administration.

Factors affecting nasal absorption-

1. Drug effect-  molecular size, lipophilic balance and ezymatic degradation in nasal cavity.

2. Nasal effect-  membrane permeability (interspecies differences), environmental pH, mucociliary clearance, colds, rhinitis etc.

3. Delivery effect-  formulation (concentration, pH, Osmolality), delivery systems (sprays, drops, gels), deposition, formulation effects in mucociliary clearances, toxic effects on ciliary functions and epithelial membranes.

Pharmacology & Toxicological considerations-

The safety of any delivery technology must be rigorously evaluated before it can be considered as a viable delivery alternative. The assessment should occur individually with both the delivery system and in combination with the active component. This is especially for trans-nasal delivery systems, which will be used systemically.

For a nasal product which contains an excipient, that affects nasal permeability, the systemic topical effects of the excipients as well as individual peptide be evaluated. Mucociliary transport rate, patho/histo morphology and ciliary beat frequency tests are the commonly prescribed test for formulations delivered by nasal route.

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Nanotechnology in Mucosal Drug Delivery Systems

5/25/2017

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A new generation of drug delivery systems is being created as a result of the ability to design nano particles and their matrixes. Nano particles are very small molecules with a diameter of 1 to 100 nm. Drugs can be coupled to or encapsulated within these specialized molecules. Advantages of using nano particles as drug delivery systems include increased drug bioavailability and precise delivery of therapeutic agents to target organs, tissues, and cells (Leary, Liu, & Apuzzo, 2006).

Nanotechnology in mucosal drug delivery systems

"Presently only 1 of 100,000 molecules of therapeutic intravenous drug reaches its desired destination. As a result of this, clinicians are faced with deciding whether to increase the drug dosage, which can lead to side effects, or reduce the dosage, which can limit the therapeutic effect" (Bulletin Board, 2008). Valuable clinical breakthroughs in using nanotechnology have already occurred in the areas of oncology, cardiovascular medicine, neurology, and orthopedics.

On the horizon are nano particles made of biodegradable and biocompatible mesoporous silicon particles designed to efficiently carry therapeutic agents to their intended site by successfully penetrating the body's immune system. These multistage nanoparticle systems deliver therapeutic agents in a manner similar to a space rocket launching from Earth through our atmosphere, in that the multilayered nanoparticle disposes of its outer layer as it moves through the body. Each layer of the nanoparticle is designed to efficiently meet and overcome each physiologic barrier that it encounters as it moves through the body. As a result, the multistage nanoparticle drug delivery system is able to successfully carry therapeutic agents to the intended site with greater efficiency and reduce the need for a higher drug dose. As an added advantage, by successfully limiting drug side effects, it is hoped that greater patient drug adherence will result (Tasciotti, Liu, & Bhavane, 2008).

Nanoshells are another exciting development in drug delivery. These molecules are hollow silica spheres covered with silver, gold, or other metals that can be chemically equipped to carry antibodies. This technology allows the nanoshell to successfully attach to specific cells within the body and deliver their payload. By precisely delivering medication to the intended site, systemic side effects can be minimized (Leary et al., 2006). Drugs may also be encapsulated within the metal nanoshells. The healthcare provider of the future will have the ability to trigger the nanoshell with an external force to release its therapeutic agent at the precise time that it reaches its intended target within the body. Infrared light and magnetic fields are currently being explored as possible triggers. This drug delivery system is expected to be especially useful in the area of oncology for the treatment of tumors because high concentrations of therapeutic agents can be delivered to the tumor, and the toxic effects to surrounding tissues can be minimized (Yih & Al-Fandi, 2006; Hafeli, 2004).

Drug-loaded erythrocytes are another nanotechnology drug delivery system under development. Erythrocytes are split open and loaded with the desired therapeutic agent. Using nanotechnology, the surface of the erythrocyte is enhanced with glutaraldehyde, antibodies, or specific carbohydrates, which increase the erythrocytes' circulation half-life, allowing for body barrier penetration and precise drug delivery. Once delivered into the patient's body, the erythrocytes circulate in the blood and reticuloendothelial systems and slowly release the intended agent (Hirlekar, Patel, & Dand, 2008).

A vaccine carrier system using nanoemulsions is currently being researched. This medication delivery system uses nanotechnology to vaccinate against HIV. There is recent evidence that HIV can infect the mucosal immune system. Therefore, developing mucosal immunity through the use of nanoemulsions may become very important in the future fight against HIV (Bielinska, Janxzak, & Landers, 2008). The oil-based emulsion is administered in the nose, as opposed to traditional vaccine routes. Research is demonstrating that genital mucosa immunity may be attained with vaccines that are administered into the nasal mucosa.

Engineered nanotechnology molecules have demonstrated superior performance over present-day monovalent drug delivery systems that have only one site of attachment. A special architectural class of nano particles called dendrimers consists of a central core with many branches that allow molecules to attach to its surface (Morrow, Bawa, & Wei, 2007). Dendrimers in research have been fashioned into sophisticated anticancer machines carrying five chemical tools: one to bind to cancer cells, a second that will fluoresce upon locating genetic mutations, a third that assists in imaging the tumor shape with x-rays, another that carries drugs to be released on demand, and one that sends a signal when cancerous cells are dead (Nova Science Now, n.d.). Additionally, in the future, dendrimers may be used to place genes in cells. It is also hypothesized that nanotechnology could be used to design specially engineered cardiomyocytes to repair damaged hearts and erythrocytes capable of delivering much higher levels of oxygen to tissues (Morrow et al., 2007).

Precise therapy parameters in the future may be maintained with implantable drug delivery and biosensing microchips. These "intelligent" systems will provide real-time therapeutic monitoring and control the time, amount, rate, and location of drug delivery. The microchip devices will contain an array of individually sealed and actuated reservoirs. The passage of a threshold level of electric current through the device will cause it to disintegrate, exposing the drugs in the reservoir to the surrounding environment (Maloney, Uhland, & Polito, 2005).

In the area of neuroscience, biosensor technology is already being used to monitor glutamate levels at the surface of living cells to provide information on the neurological damage occurring in stroke and neurodegenerative disorders and to detect the early formation of amyloid-[beta] protein found in Alzheimer's disease. "Nanomachines that could move through the body troubleshooting and repairing tiny brain or cardiovascular lesions lie in the future" (Morrow et al, 2007).

Another system, the NanoStat platform technology enables both topical anti-infective products as well as a broad range of mucosal vaccines. The technology employs high-energy, oil-in-water emulsions that are manufactured at a size of 150-400 nanometers and are stabilized by surfactants. The unique aspect of products derived from the company's NanoStat technology is that, unlike currently available therapies, NanoBio's treatments are selectively toxic to microbes while non-irritating to skin and mucous membranes. The NanoStat technology also enables a platform of nanoemulsion based mucosal vaccines. When either whole virus or a recombinant protein antigen is simply mixed with nanoemulsion and placed on the naso-pharynx, the nanoemulsion serves as a potent adjuvant, producing both mucosal immunity and systemic.

Nanotechnology is not yet here for daily use, other new methods of drug delivery continue to come to market, such as intranasal medications, pain balls, pulmonary delivery, trans-git etc.

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Carriers used in Drug Targeting-

5/9/2017

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Niosomes :

Niosomes non-ionic surfactant vesicles are similar to liposomes and can be prepared with cholesterol, a surfactant such as polysorbates (tweens) or sorbitanesters of fatty acids (spans) and water. In general, niosomes are capable of releasing the entrapped drug slowly Methotrexate has been reincorporated into niosomes and the nature of the surfactant used seemed to affect the amount of methotrexate entrapped into the niosomes.

Furthermore, the pharmacokinetics of the methotrexate loaded niosomes in sarcoma S-180 bearing mice were comparable to those of the free drug.  The methotrexate plasma levels were higher and the rate of elimination from plasma was slower when the methotrexate-loaded niosomes were administered to tumor-bearing mice as compared with the free drug.

In conclusion, several cytotoxic agents, which had never been formulated before due to their low aqueous solubility, have been successfully incorporated into liposomes,  thereby decreasing the toxicity of the former formulation of the drug itself.  However, more research has to be performed to develop liposomes with higher chemical and physical stability to present degradation during extended storage.

Micro encapsulation System:

Micro encapsulation involves the application of a thin film of material and micronized solid or liquid to produce discrete units ranging in size from less than 1 m to several millimeters.  The products of micro encapsulation can be classified into nano particles (200-500nm), micro dispersions (0.5-m), micro spheres (1-100 m) and microcapsules (> 100 m).  Numerous methods have been used to prepare microencapsulated systems. These include pan coating, fluidized bed, spray drying, solvent evaporation, inter facial polymerization and coacervation techniques.

Microencapsulated systems often possess controlled release characteristics and less toxicity as compared to free drug.  These systems have been studied to target cytotoxic drugs viz. actinomycin D, 5-Fluorouracil, Doxorubicin, Vinblastin, etc.  However, they are unsuitable for formulation of thermolabile drugs.

Cellular Carriers:

Erythrocytes, leukocytes, platelets, islets, hepatocytes, and fibroblasts, all have been suggested as potential carriers for drugs and biological substances.  They can be used to provide slow-release of entrapped drugs in the circulatory system, to deliver drugs to a specific site in the body, as cellular transplants to provide missing enzymes and hormones (in enzymes-hormone replacement therapy), or as endogenous cells to synthesize and secrete molecules that affect the metabolism and function of other cells.  Because these carriers are actual cells, they produce little or no antigenic response, and when old or damaged, they, like normal cells, are removed from the circulation by macrophages.  Another important feature of these carriers is that, once loaded with drug, they can be stored at 4o C for several hours to several days, depending on the storage medium and the entrapment method used.

Since erythrocytes, platelets, and leukocytes have received the greatest attention, the discussion that follows will be limited to these carriers.  Fibroblasts and hepatocytes have been specially used as viable sources to deliver missing enzymes in the management of enzyme deficiency diseases, whereas islets are useful as a cellular transplant to produce insulin.

Erythrocytes:

Erythrocytes have been suggested as potential carriers for a number of biologically active substances including drugs, nucleic acids and enzymes.  They can be used as storage depots for sustained-drug release or potentially be modified to permit targeting to specific cell types in the blood (e.g. direct targeting to cells in leukemia).

Platelets:

Platelets have been used as a carrier for several biological substances and drugs useful in the management of various hematological diseases.  Platelets can accumulate drugs by selective active transport.  Certain drugs viz. angiotensin, hydrocortisone, imipramines, vinca alkaloids, (vinblastine and vincristine) and many other drugs are known to bind platelets.

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Nanotechnology – A drug delivery promise for scar-less wound healing.

1/1/2015

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Nanotechnology represents an ‘Innovative direction’. It’s not the future as it’s already present in the pharmaceuticals, natural products realm and it’s expected to grow with time.

Injectable and dermatology spheres have successfully employed Nanotechnology to product development. Yet, there is still a wide gap in wound- healing dermatology.

The wound healing process consists of four highly integrated and over lapping phases- hemostasis, inflammation, proliferation and time remodeling. For a wound to heal successfully, all four phases of this process must occur in the proper sequence, at a specific time and continue for specific duration at optimal intensity.

Conventional wound-healing products, in majority of instances, do tend to leave scar behind. This is the case both with pharmaceutical and natural products.

For example Curcumin derived from spice turmeric, has traditionally been known to be excellent with wound healing even when administered in the raw powder form. For a formulator, the challenge is water- insoluble nature of turmeric as well as the staining property of curcumin.

Applying Nanotechnology to formulation development of turmeric products, is expected to circumvent the difficulties inherent in curcumin administration, enabling delivery of this therapeutic substance. Furthermore, curcumin in a Nano vesicle will assist clear infection as well as accelerate wound healing by sitting more evenly on the wound bed.

Research findings have shown that the growth of tissue and extent of scar formation can be controlled by modulating the stress at a wound site. And Nanotechnology shows promise for delivering many advanced wound- healing agents.

With Nanotechnology, you can have multiple therapeutic agents in one platform that can work synergistically in wound therapy. For example, combining turmeric with a collagen regenerating/ remodeling ingredient will further augment the healing process, wound repair and tissue regeneration and bring- on scar less wound healing.

However, the key to using Nanotechnology correctly to pharmaceuticals and natural products is having a complete understanding of - Which Nano materials can accelerate wound- healing, how and when to use them and which wound healing agents to incorporate viz. immunomodulatory, anti-microbials anti-inflammatory etc.

Nanotechnology is indeed a “magic bullet’ in developing safe, effective and targeted science based products.

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Nanotechnology in Pharmaceutical Research- Magnetic fields drive Paclitaxel -loaded nanoparticles to reduce blood vessel blockages.

4/28/2010

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Scientists and engineers have used uniform magnetic fields to drive iron-bearing nanoparticles to metal stents in injured blood vessels, where the particles deliver a drug payload that successfully prevents blockages in those vessels.

In this animal study, the novel technique achieved better results at a lower dose than conventional non-magnetic stent therapy.

Conducted in cell cultures and rats, the research is the latest in a series of studies at The Children's Hospital of Philadelphia demonstrating the feasibility of magnetically guided nanoparticles as a new delivery platform for a variety of possible therapeutic cargos: DNA, cells and drugs. The findings may set the stage for a new medical tool, called vascular magnetic intervention.

"This can become a major platform technology for delivering drugs and other agents to specific sites where they can produce benefits in diseased or injured blood vessels," said study leader Robert J. Levy, M.D., the William J. Rashkind Endowed Chair in Pediatric Cardiology at The Children's Hospital of Philadelphia.

The research appears in the Proceedings of the National Academy of Sciences, published online, Levy's group from Children's Hospital collaborated with engineers and scientists from Drexel University, Northeastern University and Duke University.

Levy's work introduces a new delivery system to an existing medical technology—catheter-deployed stents. Patients with heart disease commonly receive such stents, narrow metal scaffolds that widen a partly clogged blood vessel. These stents are often coated with antiproliferative drugs such as paclitaxel. Paclitaxel inhibits the accumulation of smooth muscle cells within the stent that cause an obstruction.

However, current drug-eluting stents have their limitations. They contain a fixed dose of medication, good for just one release. In a significant number of patients, reobstruction occurs. Levy's magnetically guided system broadens the possibilities for stents, since magnetic targeting permits using higher doses, redosing if problems recur and using more than one type of agent to treat a blood vessel with a stent.

Levy made use of nanotechnology—the application of extremely small materials. His lab team created nanoparticles, approximately 290 nanometers across, made of a biodegradable polymer and impregnated with magnetite, an iron oxide. (A nanometer is one millionth of a millimeter; these nanoparticles are ten to 100 times smaller than red blood cells.). The magnetite in the particles responds strongly to a magnetic field. Being biodegradable, the particles break down safely in the body after releasing their payload.

Levy's team first implanted stainless steel stents into the carotid arteries of live rats. After injecting paclitaxel-loaded nanoparticles into the rat's arteries through a catheter, they produced a uniform magnetic field around each rat for five minutes. The magnetic field, comparable to that produced by existing MRI machines, but one-tenth as strong, magnetized both the stents and the nanoparticles, and drove the particles into the stents and the nearby arterial tissue.

The researchers inserted stents and nanoparticles into a group of control rats, but without using a magnetic field. Five days after receiving the nanoparticle infusion, the magnetically treated animals had four to 10 times as many particles in their stented arteries as the control animals.

Moreover, using magnetic fields to concentrate the treatment had a lasting effect. Fourteen days after using the magnetic field and a single dose of magnetic nanoparticle-encapsulated paclitaxel, the researchers found the rat arteries had significantly lower restenosis than found in arteries of control rats that had no magnetic treatment.

Over the past several years, Levy and colleagues have shown similar proofs of concept in other animal studies, using magnetically guided nanoparticles to deliver gene therapy and therapeutic endothelial cells to arterial stents. The technique is versatile, Levy says, adding that it could also deliver a broad range of effective therapeutic agents.

Stents and magnetic fields might also deliver combination therapies. Nanoparticles could carry different agents simultaneously or at different times. Since the stents remain in place, physicians could retreat patients, delivering therapeutic agents through catheters under magnetic guidance. Because the magnetic effect concentrates its delivery package at the specific site of a stent, physicians could achieve stronger effects with lower overall doses of a given agent. Contributing to the technique's efficiency, the polymer-based nanoparticles provided sustained drug release over the 14-day course of the study.

Levy envisions a future therapy called vascular magnetic intervention, in which a patient would receive regular treatments from a vascular surgeon or interventional cardiologist who delivers doses of therapeutic nanoparticles under a low-level, uniform magnetic field.

Although currently stents are primarily used for heart patients, Levy cited a great unmet need among the millions of patients with chronic peripheral artery disease. In diabetes patients with poor circulation, for example, drug-eluting stents have had "disappointing results," Levy says, because leg arteries are larger than coronary arteries, and insufficient drug doses are included in the stent coating. "Our technique offers opportunities for a novel approach in which we can vary doses and repeat the treatments," he adds.

In children, stents are used to mechanically enlarge anatomic structures for conditions such as peripheral pulmonary artery stenosis, the heart defect coarctation of the aorta, and atrial septal defects created by interventional techniques to provide oxygenated blood. Levy suggests the magnetically guided nanoparticles might deliver drugs that could improve the outcomes in each of these settings, as well as a number of other stent-based interventions used in pediatric cardiology.

For the magnetically-guided nanoparticles that Levy studies, potential clinical applications are still in the future, but possibly not too distant. He expects to partner with clinical researchers in the next few years to bring vascular magnetic intervention closer to clinical reality. "This technique is poised to become a new platform for interventional therapies that could be safer and more effective than the current treatments," he said.

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Nanotechnology- A new tool in pharmaceutical research?

4/26/2010

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Who's regulating nanotechnology?

Nanotechnology and its applications are so small that it can be hard to get your head around, but there are more than 1,000 products with nanomaterials already on the market, so we'd better get a handle on this quick.

Nanoscale science and technology manipulate matter at the level of 1-300 nanometers (or billionths of a meter) and claim a seemingly amazing array of applications for medicine, technology, energy and food. Pulitzer Prize-winning reporter Andrew Sheider's recent investigative series "The Nanotech Gamble" lays bare the potential health and environmental risks and extent to which largely unregulated nanotech products are already on the market, and in the food supply, without our knowledge.

Given the risks and speed with which nanotechnology is entering the marketplace, U.S. states are starting to explore what they can do in light of federal inaction. In testimony before the Minnesota state legislature, IATP's Steve Suppan outlines the regulatory holes at the Food and Drug Administration and the Environmental Protection Agency, which thus far have largely given nanotechnology a free ride.

On April 15, the University of Minnesota hosted Governing Nanobiotechnology: Reinventing Oversight in the 21st Century. Academics, private industry, public interest representatives and government regulators grappled with the particular regulatory challenges posed by nanotechnology (videos of presentations coming soon).

As Steve points out in his testimony to state legislators, traditional regulation targets pollutants partially in terms of volume: that approach won't work for nanotechnology. "The quantity of nanomaterials that may cause environmental and/or public health harm will be much smaller in volume than what [...] has traditionally been inventoried. Prioritizing when and where to monitor pollutants will be a difficult task because potential risks of nanomaterials are not indicated simply by their size but also by their configuration and shape."

When scientific advancement overtakes our ability to regulate it's time to take a step back. The U.S. government's National Nanotechnology Initiative spent an estimated $1.8 billion developing new nanotech products in 2009. Little more than one percent of that taxpayer investment is dedicated to research to protect consumers and nanotechnology workers from potential environental, health and safety hazards of nanotechnology products. This is an unacceptably nano-sized start to a huge regulatory challenge.

Nanopatch tipped to replace syringe :

Researchers have used nanotechnology to discover a far more effective and less painful vaccination technique than the syringe.

University of Queensland Professor Mark Kendall's bio engineering and nanotechnology team have developed the Nanopatch - which uses 100 times less vaccine than a syringe and is smaller than a postal stamp. The patch is tipped to revolutionise vaccination programs in both industrialised and developing nations, which must overcome issues with vaccine shortages and distribution.

Prof Kendall said being both painless and needle-free, the Nanopatch offers hope for those with needle-phobia, as well as improving the vaccination experience for young children. "The Nanopatch targeted specific antigen-presenting cells found in a narrow layer just beneath the skin surface and as a result we used less than one-hundredth of the dose used by a needle while stimulating a comparable immune response," Prof Kendall said, "Our result is 10 times better than the best results achieved by other delivery methods and does not require the use of other immune stimulants, called adjuvants, or multiple vaccinations."

He said developing nations would particularly benefit as it does not need refrigeration and can be administered by non-professionals. Despite its small size, the Nanopatch comprises several thousand densely packed projections invisible to the human eye.

The influenza vaccine was dry coated onto these projections and has already been tested on the skin of mice. "By using far less vaccine we believe that the Nanopatch will enable the vaccination of many more people, Prof Kendall said, "A government might provide vaccinations for a pandemic such as swine flu to be collected from a chemist or sent in the mail."

Prof Kendalls team includes researchers from UQ's Diamantina Institute for Cancer, Immunology and Metabolic Medicine and Faculty of Health Sciences, as well as the University of Melbourne. He said after about five years worth of work the project was at about the halfway point of hitting the market, with the next stage to be human clinical trials. "To the public this might seem like a long time, but in the vaccine world this is quite quick," he said.

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