Oral delivery system could make vaccinations needle-free

Photo: UC Berkeley

Patients could one day self-administer vaccines using a needleless, pill-sized technology that jet-releases a stream of vaccine inside the mouth, according to a proof-of-concept study conducted at UC Berkeley.

The study did not test vaccine delivery in people, but demonstrated that the technology, called MucoJet, is capable of delivering vaccine-sized molecules to immune cells in the mouths of animals. The technology is a step toward improved oral vaccine delivery, which holds the promise of building immunity in the mouth’s buccal region of cells, where many infections enter the body. When patients hold the MucoJet against the inside of their cheek, the device releases a jet stream that directly targets the buccal region. This region is rich in immune cells but underutilized in immunology because of the challenge of efficiently penetrating the thick mucosal layer in this part of the oral cavity with existing technologies, such as the oral spray often used for influenza vaccination.

In laboratory and animal experiments, the research team showed that the MucoJet can deliver a high-pressure stream of liquid and immune system-triggering molecules that penetrate the mucosal layer to stimulate an immune response in the buccal region. The jet is pressurized, but not uncomfortably so, and would remove the sting of needles.

“The jet is similar in pressure to a water pick that dentists use,” said Kiana Aran, who developed the technology while a postdoctoral scholar at Berkeley in the labs of Dorian Liepmann, a professor of mechanical and bioengineering, and Niren Murthy, a professor of bioengineering. Aran is now an assistant professor at the Keck Graduate Institute of Claremont University.

The portable technology, designed to be self-administered, stores vaccines in powder form and could one day enable vaccine delivery to remote locations, but years of further study are needed before the device would be commercially available.

Source: UC Berkeley

Delivering Vaccines Via Drones

Drone to deliver vaccines
Picture: Johns Hopkins University

Vaccines have come a long way scientifically, technologically and economically. But in one crucial aspect—distribution—they are still lagging behind.

“Many existing vaccine supply chains in low- and middle-income countries were established in the late 1970s and ’80s and have since remained relatively unchanged even though populations, diseases, and vaccines have changed substantially,” says Bruce Y. Lee, MD, MBA, director of operations research at the International Vaccine Access Center at the Bloomberg School.

It’s long been a challenge to distribute vaccines over great distances in treacherous conditions. Now, thanks to technological improvements, unmanned drones have been floated as a possible solution. But is this strategy cost-effective?

To find out, Lee and his team used their HERMES computer simulation model to compare the delivery of vaccines through traditional land-based transportation (a combination of trucks, motorbikes and public transit) to that of unmanned drones. The researchers factored in road conditions, availability of refrigeration, weight, space, weather and other conditions in the simulations.

They found that using drones increased vaccine availability, potentially reaching 96 percent of the targeted population, versus 94 percent for land-based transportation.

Drones also delivered a savings of 8 cents per vaccination, translating into a 20 percent cost savings overall.

Lee and the HERMES team pub- lished their findings in Vaccine in June 2016. Next, Lee says, drone manufacturers are conducting larger-scale pilot studies with different countries and conditions. These studies will evaluate drones’ abilities to meet the guidelines laid out by the HERMES model and to provide additional data to update the simulation model.

The potential impact drones can have on vaccination rates is significant, says Lee, an associate professor in International Health. “They could be particularly valuable when there is more demand for certain vaccines than anticipated and immunization locations must place urgent orders.”

Source: Johns Hopkins University

Particles carry more drugs hold potential for targeted cancer therapy

Nanoparticles offer a promising way to deliver cancer drugs in a targeted fashion, helping to kill tumors while sparing healthy tissue. However, most nanoparticles that have been developed so far are limited to carrying only one or two drugs.

MIT chemists have now shown that they can package three or more drugs into a novel type of nanoparticle, allowing them to design custom combination therapies for cancer. In tests in mice, the researchers showed that the particles could successfully deliver three chemotherapy drugs and shrink tumors.

In the same study, which appears in the Sept. 14 issue of the Journal of the American Chemical Society, the researchers also showed that when drugs are delivered by nanoparticles, they don’t necessarily work by the same DNA-damaging mechanism as when delivered in their traditional form.

That is significant because most scientists usually assume that nanoparticle drugs are working the same way as the original drugs, says Jeremiah Johnson, the Firmenich Career Development Associate Professor of Chemistry and the senior author of the paper. Even if the nanoparticle version of the drug still kills cancer cells, it’s important to know the underlying mechanism of action when choosing combination therapies and seeking regulatory approval of new drugs, he says.

Using a method developed by Hemann’s lab, the researchers then investigated how their nanoparticle drugs affect cells. The technique measures cancer drugs’ effects on eight genes that are involved in the programmed cell death often triggered by cancer drugs. This allows scientists to classify the drugs based on which clusters of genes they affect.

The researchers found that nanoparticle-delivered camptothecin and doxorubicin worked just as expected. However, cisplatin did not. Cisplatin normally acts by linking adjacent strands of DNA, causing damage that is nearly impossible for the cell to repair. When delivered in nanoparticle form, the researchers found that cisplatin acts more like a different platinum-based drug known as oxaliplatin. This drug also kills cells, but by a different mechanism: It binds to DNA but induces a different pattern of DNA damage.

The researchers hypothesize that after cisplatin is released from the nanoparticle, via a reaction that kicks off a group known as a carboxylate, the carboxylate group then reattaches in a way that makes the drug act more like oxaliplatin. Many other researchers attach cisplatin to nanoparticles the same way, so Johnson suspects this could be a more widespread issue.

Source: Massachusetts Institute of Technology



Mayo Clinic Proceedings Publishes New Insulin Injection and Infusion Recommendations

Medical Journal ‘Mayo Clinic Proceedings’ published new insulin delivery recommendations for health care professionals caring for insulin-using patients, including the results from the largest injection technique survey ever performed for people with diabetes.

Three articles will appear in the September print issue of the publication – with new research showing that many patients with diabetes are using insulin incorrectly and not getting the maximum benefit from this life-saving medication. Proper injection and infusion technique is critical to insulin’s consistent action and may be as important as the medication or diet and activity. These findings provide a clear roadmap for better clinical management of insulin use for people with diabetes and for their health care providers.

Dr. Kenneth Strauss, co-author and medical director, BD Europe stated, “FITTER and these publications set new standards for insulin delivery.  Tools are embedded in these publications, which will allow patients and professionals to quickly translate them into everyday practice.  If these recommendations become routine practice, we should soon see the improved outcomes that come from optimized insulin delivery.”

The analysis of this landmark injection technique survey is the result of a BD (Becton, Dickinson and Company) sponsored international workshop known as the Forum for Injection Technique & Therapy Expert Recommendations (FITTER). This international congress included 183 diabetes experts from 54 countries and took place October 2015 in Rome. Two of the papers published in Mayo Clinic Proceedings address the key findings from this injection technique survey and a third paper presents the new insulin delivery recommendations, intended to help shape local and regional injection guidelines around the world.

Insulin Injection Technique Survey Key Takeaways:

  • Many patients taking insulin are using needles that are longer and thicker than recommended, and are reusing the needles frequently.
  • One-third of those taking insulin have nodules or bumps in the fat tissue at their injection sites (a condition known as lipohypertrophy, or lipos). This is associated with incorrect rotation of injection sites and is also problematic with insulin infused via pumps.
    • If patients inject into lipos, the absorption of insulin is blunted and highly variable. This may cause patients to react by injecting more insulin, which puts them at risk of unexpected glucose swings and dangerous hypoglycemia.
    • Despite using more insulin, patients with lipos have worse glucose control, increasing their risk for eye, kidney and nerve complications.

The third publication, “New Recommendations for Insulin Delivery” is based on these survey findings as analyzed by participants of the FITTER international congress.

The new FITTER recommendations include:

  • Use the shortest available pen needle (currently 4mm) or syringe needle (currently 6mm) for all injecting patients, regardless of age, sex or body size.
    • The shortest needle length is less painful, has higher patient acceptance and gives comparable glucose control.
    • By contrast, excessively long needles increase a patient’s risk of intramuscular injections, which can accelerate insulin uptake and action, increasing glucose variability and risk of hypoglycemia.
  • Correct rotation of injection sites can reduce the frequency of lipohypertrophy. Such reductions should improve glycemic control and clinical outcomes, reduce insulin consumption and thereby lower health care costs.
  • Limit use of pen needles and syringes to one-time, as reusing needles is not an optimal injection practice because they are no longer sterile after use.

The new FITTER recommendations also contain important sections dealing with optimal insulin pump and infusion set guidance, as well as recommendations for use of safety-engineered injection devices for people who give injections, such as healthcare workers.  In conclusion, adherence to these recommendations may lead to better injection and infusion experience for patients, safer injections by HCWs, and improved glucose control, which reduces the risk of long-term complications and saves health care dollars.

“BD’s purpose of advancing the world of health expands far beyond the products we make. We partner with health care professionals around the world to publish evidence-based practices in peer-reviewed publications and create educational tools that can help people with diabetes achieve better clinical outcomes,” said Dr. Laurence Hirsch, co-author and worldwide vice president of Medical Affairs for BD Diabetes Care. “These new recommendations will help health care professionals and people with diabetes who take insulin to better manage their treatment.”

Dr. Anders H. Frid, lead author and Diabetologist at the Skane University Hospital, Malmö in Sweden added, “For more than 30 years, I have been studying injection sites, injection technique and insulin absorption. It is a wonderful accomplishment to now have comprehensive and evidence-based recommendations around proper needle use and good injection practices published in a major journal for health care professionals and people with diabetes around the world to access.”

Source: Becton, Dickinson and Company (BD)


BD Cited As Infusion Pump EMR Integration Leader In KLAS Report

BD announced that its Alaris™ System infusion platform was cited as having the most customers live with bidirectional electronic medical record (EMR) integration, which health care providers said is the most important next step for improving safety to help reduce pump-programming errors in the Smart Pumps 2016: The Quest for Patient Safety report issued by KLAS.

The report from KLAS, an organization that independently monitors health care information technology performance through the active participation of thousands of health care organizations, also stated that BD has the “most comprehensive pump platform.” The Alaris System from BD has the most customers live with EMR integration and is reported to be the only infusion platform to achieve EMR integration with syringe pumps.

“This recognition is important because it comes directly from the health care providers who use our products every day,” said Mike Garrison, vice president and general manager of worldwide Infusion Solutions for BD. “We continue to invest in innovation to ensure our products are at the forefront of technology to help improve patient safety and care efficiency.”

The report also states that a large number of BD customers achieve high drug library compliance, which many credit to BD’s reports and guidance. In addition, the report shows that actionable insights are more highly valued over basic reporting, and BD is leading in this transformation. More customers use BD reports and analytics to drive outcomes than any other infusion pump vendor.

Earlier this year, the Alaris System was named Best in KLAS for Smart Pumps in The 2015 Best in KLAS: Medical Equipment report that stated that providers believe that BD is better positioned for the future in regard to interoperability with electronic medical records (EMRs), and customers appreciate the added benefit of having patient-controlled analgesia (PCA) pumps and syringe pumps on a single platform.

A press release can be found from BD website.

Researchers Improve Computer Modeling for Designing Drug-delivery Nanocarriers

A team of University of Pennsylvania researchers has developed a computer model that will aid in the design of nanocarriers, microscopic structures used to guide drugs to their targets in the body. The model better accounts for how the surfaces of different types of cells undulate due to thermal fluctuations, informing features of the nanocarriers that will help them stick to cells long enough to deliver their payloads.

The study was led by Ravi Radhakrishnan, a professor in the departments of bioengineering and chemical and biomolecular engineering in Penn’s School of Engineering and Applied Science, and Ramakrishnan Natesan, a member of his lab.

Also contributing to the study were Richard Tourdot, a Radhakrishnan lab member; David Eckmann, the Horatio C. Wood Professor of Anesthesiology and Critical Care in Penn’s Perelman School of Medicine; Portonovo Ayyaswamy, the Asa Whitney Professor of Mechanical Engineering and Applied Mechanics in Penn Engineering; and Vladimir Muzykantov, a professor of pharmacology in Penn Medicine.

It was published in the journal Royal Society Open Science.

Nanocarriers can be designed with molecules on their exteriors that only bind to biomarkers found on a certain type of cell. This type of targeting could reduce side effects, such as when chemotherapy drugs destroy healthy cells instead of cancerous ones, but the biomechanics of this binding process are complex.

Previous work by some of the researchers uncovered a counter-intuitive relationship that suggested that adding more targeting molecules on the nanocarrier’s surface is not always better.

A nanocarrier with more of those targeting molecules might find and bind to many of the corresponding biomarkers at once. While such a configuration is stable, it can decrease the nanocarrier’s ability to distinguish between healthy and diseased tissues. Having fewer targeting molecules makes the nanocarrier more selective, as it will have a harder time binding to healthy tissue where the corresponding biomarkers are not over-expressed.

The team’s new study adds new dimensions to the model of the interplay between the cellular surface and the nanocarrier.

“The cell surface itself is like a caravan tent on a windy day on a desert,” Radhakrishnan said. “The more excess in the cloth, the more the flutter of the tent. Similarly, the more excess cell membrane area on the ‘tent poles,’ the cytoskeleton of the cell, the more the flutter of the membrane due to thermal motion.”

The Penn team found that different cell types have differing amounts of this excess membrane area and that this mechanical parameter governs how well nanocarriers can bind to the cell. Accounting for the fluttering of the membrane in their computer models, in addition to the quantity of targeting molecules on the nanocarrier and biomarkers on the cell surface, has highlighted the importance of these mechanical aspects in how efficiently nanocarriers can deliver their payloads.

“These design criteria,” Radhakrishnan said, “can be utilized in custom designing nanocarriers for a given patient or patient-cohort, hence showing an important way forward for custom nanocarrier design in the era of personalized medicine.”

Details can be found from University of Pennsylvania website.