How does needle free injection work

Since the invention of drugs was capable of curing ailments, newer and better method of delivering them has been sort after.

NFIT are novel ways of direct transfer of medicine through the skin, without breaching the integrity of the skin or even piercing it. These devices can be used to drive medicaments into the muscle too. These systems are virtually painless as they avoid the use of conventional needles. Springs have been used to harbor energy and have been proven to be quite effective in powering NFIT devices. For NFITs, energy storage and further transmittance via spring is one of the easiest and simplest.

The basic issue with respect to the design of the spring is that the force provided by the spring will reduce in proportion to the distance over which the load has been applied as according to the Hook's law. The technology uses an erbium-doped yttrium garnet laser the one used in the care of laser resurfacing of the skin to drive a very fine and precise stream of drug or medicament with the right amount of force. The laser is integrated with an adapter which holds the drug to be administered.

The device also contains a chamber for water which is used to drive the medicine; however, the arrangement is so done that the drug is separated from the driving fluid water with the help of a membrane. The laser pulse of a wavelength of about nm is emitted, which has a life span of about millionth of a second. It attacks the driving fluid generating a vapor inside the fluid.

The research team in association with a major company is still working on the technology to develop better and more advanced variants of this technology. Commercial spring powered jet injectors offer little to no control over the pressure applied to the drug during the time of the injection; also these devices are often loud and sometimes painful.

The force required to propel the drug so as to have a penetrating effect can also be generated by energy in various forms. Researchers at MIT have engineered an NFIT device which uses Lorentz force to push a piston forward ejecting the drug at very high pressure and velocity almost equal to that of sound in air. The main component of the device is the Lorentz force actuator which facilitates the entire process.

The design of the device is built around a Lorentz force actuator which consists of a small and powerful magnet which is surrounded by a wire coil that remains attached to a piston which is inside a drug ampoule. When current is applied, it interacts with the magnetic field so as to produce a force, which pushes the attached piston forward, while the stream of the formulation from the device is forced out as thin as the mosquito's proboscis.

The amount of current supplied can be very well regulated enabling the speed of the coil to come under our regulation. This would finally control the velocity with which the drug is ejected. The research team has even demonstrated the device to act in a high pressure phase when the drug penetrates deeper into the skin at desired strength and in a low pressure phase where the drug is delivered in a lower stream so as to be absorbed by the surrounding tissues.

This capability of the device has made it be a versatile NFIT system suitable for corneal drug application and also fit for pediatric use. Gas, as a power source will be less suitable for reusable devices unless special arrangement and design alterations or component modifications may be made such that the pressure is not lost, and the spring is reset for each injection, still, gas powered NFITs have greater scope since compressed gas offer higher energy density than a metal spring.

Gas powered devices tend to be either single use or need a periodic replacement of the gas cartridge. Some devices employs gas as a simple spring where the stored gas accelerates the piston there are portable and compact, however, developing a gas spring which retain a specific proportion of the gas to work at the lapse of its shelf life is a major challenge. To overcome such challenges, an alternate method has been developed which uses carbon dioxide liquefied at the storage temperature and pressure.

This may affect the performance of the device if a broader operating temperature range is desired. This problem can be sorted out by using a pressure regulator. Further research has led to the evolution of reusable, sophisticated and comparatively more portable gas powered NFITs as in such systems one developed by Team Consulting Ltd.

The complete efficacy of this system is yet to be established, and data published. Major industries Cross-Ject and BioValve working for the development of NFIT systems have employed a technique of gas generation chemically in which the gas is produced at a reproducible and predictable rate to power the device.

Shock waves are generated by any sudden release of energy. These disturbances carry energy and can be propagated through a medium. The drug is forced into the skin while the integrity of the skin remains intact. If the technology developed by IISc proves to be successful, the institute will offer cheaper, noninvasive technologies which will not only arrest the incandescence needle stick injuries but would also limit infections at healthcare centers.

The mechanics involved in liquid NFITs is so complex that the recent studies have been carried out to understand the complete procedure of it. Delivering fluid from NFIT involves a thorough application of fluid mechanics. The steps involved are:[ 17 ]. Exact pressure: The fluid must be forced at an optimum pressure, stronger enough that it keeps the holes in the skin open and consistent enough that it avoids the resealing of the holes.

Channel drilling: The initial pulse of the fluid drill a channel into the fat layer deep enough that the dose is drifted from the hole into the skin. Quicker pressure fall: The pressure drops quickly and sufficiently so that the fluid may not penetrate the muscles underlying the skin.

Powder needle free injection depends on being able to formulate the particles of sufficient density and accelerating them to sufficient velocity strong enough to penetrate the skin and in a quantity sufficient enough to reach the therapeutic dose levels.

Conversion of the drug either pure or along with excipients into hard particles of nm in diameter, with a density approximately the same as a crystalline drug. Coating the drug onto gold spheres which may act as a vector of few micrometers in diameter, this method is mostly applicable to DNA vaccines. Drug delivery through this system is limited only to those candidates with an effective dose of about 1 mg max. Since in powder drug delivery through NFIT systems, it is difficult to predict the proportion of dose that is difficult to determine the proportion of dose that is to be delivered to the epidermis, also the maximum payload for a 20 mm diameter target area of skin is about mg.

This technology is highly suitable for DNA vaccines and the delivery of local anesthetic to the skin and oral mucosa. Highly advanced compared to the prior developed into this variants of the NFITs, the drug is processed into a long thin depot having sufficient mechanical strength strong enough to transmit a driving force to a pointed tip which may be formed either of an inert material or medicament itself. Generally, a depot is in the form of the cylinder measuring around 1mm in diameter and few millimeters in length.

This dimension may be small enough to limit the payload, but the quantity of the payload is sufficient enough for many new therapeutic proteins, antibodies, and other smaller molecules. The depot is strong enough to puncture the skin when punched with the sharp tipped punch by applying a pressure of the order of mega Pascal MPa.

For a depot preparation of around 1 mm, only a few Newton's of force are required. The working of nano-patch or micro-projection depends on the use of an applicator to deliver the drug through the skin. Nano-patch projections are invisible to the naked eye and thereof are not anticipated to inflict fear into the people.

Drug delivery using nano-patches have been highly efficient with respect to vaccines. Nano-patches enable the vaccine to reach the key immune cells located below the skin surface while the entire process is pain free. Sandpaper aided drug delivery has been successful in increasing the skin permeability, for several vaccines and other methods of Microdermabrasion have been used to facilitate the movement of drugs such as lidocaine, 5-flurouracil.

The lipophilic nature of skin debars several salts and other molecules from entering the skin. By iontophoresis, a small electric current of about 0. For successful drug delivery by iontophoresis, both the quantum of charge positive and negative and type of the drug must be compatible with the process.

Excipients in the drug and condition of the skin need to be considered too. Iontophoresis has also been modified so as to remove molecules from the blood circulation. GlucoWatch, a needless procedure involves a reverse iontophoresis technique to monitor blood glucose level. These patches are pressed onto a person's skin while the spikes pierce the outer most layer of the skin so as to deliver the drug, while the piercing is not deep enough to hit the blood vessels or even the pain receptors so as to cause pain.

Different types of micro-needles have been developed from the sophisticated metallic to plastic ones. Researchers have revealed the drug delivery mainly vaccines have been more efficient when administered via micro-needle patch than the traditional intra-muscular injection, since larger number of dendritic cells which are more susceptible to vaccines are located in the skin.

Even micrograms level of drugs can be delivered using micro-needle based drug delivery system. This makes it the most suitable choice for highly potent and small molecules or peptides. Micro-needle patches have not only proven to be highly effective but have even shown better patient compliance. However, certain limitations are associated with the use of micro-needle patches. In cases, if the needle itself is made of the drug, the formulation must have required physico-chemical property to maintain a sharp tip for adequate skin penetration.

The depth of penetration of the micro-needle may differ from person to person, based on thickness, toughness of the skin and reproducibility of the application. Movements of the body or the body part upon which the patch is applied may lead to dislodging of the needle.

These systems have been employed to deliver comparatively newer, DNA-based vaccines to the intradermal layer. One of the most developed NFIT systems employed for intramuscular drug administration. Drug delivery via this system is the deepest among all.

Drug delivery through NFIT devices has been most successful for vaccination. Certain therapeutic proteins including the human growth hormones have been administered by this system. The medicament is delivered to the adipose layer just below the skin. Nonprefilled devices need to have a longer shelf life which can be attained by the stable power source. The mechanics of the device must be so as to enable it being trigged even after years of storage in varied storage conditions.

When talking about the prefilled NFIT system, the following points need to be considered over the entirely intended shelf life:[ 33 ]. The leachable profile into the formulation from the contact component of the device must not be excessive, rather acceptable. The purity composition and concentration shall not be compromised throughout the intended shelf life at any case.

Furthermore, the diameter of the nozzle is significantly smaller than that of a conventional needle. Collectively, these factors indicate that the shear stresses experienced by drugs inside a jet nozzle are significantly higher than those in a needle. However, the drugs experience high shear in jet injectors for a much shorter period than they do in a needle. Detailed studies are therefore necessary to characterize shear-induced damage in the jet injector. A large body of literature on successful delivery of proteins and DNA, however, suggests that drug disintegration in jet injectors is not an overwhelming concern.

Needle-free liquid jet injectors have had a significant impact on drug and vaccine delivery. They hold a prominent place in history as an important component of mass immunization programmes and as the first large-scale needle-free method for macromolecule delivery. Jet injectors DCJIs provide an attractive alternative to injections. For many needle-phobic patients, they reduce anxiety and offer a preferred mode of delivery.

They also eliminate issues related to needles such as accidental punctures and sharps disposal. Compared with other needle-free approaches such as patches, sprays and pills, jet injectors offer an advantage that they can operate with existing formulations designed for needle-based injections.

This brings significant cost savings through reduced times of development and clinical trials. However, needle-free liquid jet injectors, despite more than 50 years of clinical use, have not reached their full potential. Several factors contribute to this: occasional pain, discomfort and local reactions 61 , 74 , inconvenience of use compared with injections and cost. Limitations of current jet injectors should provide guidelines for future research and development.

Fundamental in vitro studies have shown significant variability in jet penetration depending on skin properties The largest source of variability is likely to be the mechanical properties of the skin, which has a significant role in the outcome of jet injections. Strategies are required to counteract this variability and obtain consistent injections.

The development of such strategies requires a better understanding of the fundamental mechanisms of jet injections. Particular emphasis should be placed on understanding which mechanical properties of the skin affect jet injections.

A predictive model describing this phenomenon will also prove valuable. The occasional pain and bleeding associated with jet injectors also needs to be addressed. The origin of occasional pain is not clear. It is possible that occasional pain and bleeding are associated with variability in a jet's penetration depth. Deep penetration of jets could result in interactions with nerves and blood vessels in the dermal and sub-dermal layer.

By restricting jet penetration to the superficial layers of skin, direct interactions with nerves or blood vessels might be potentially minimized. It is also possible that variability in pain is associated with lateral density of nerves and blood vessels. In that case, the use of smaller nozzle diameters could prove helpful. Currently, there are few differences among the jet parameters used in various commercial jet injectors.

More studies are necessary to explore jet performance outside this range. Particular attention needs to be focused on using smaller nozzle diameters. Reports indicate that patients prefer smaller nozzles, possibly because they are associated with reduced adverse effects 10 ; however, mechanistic studies show compromised completeness with smaller nozzles Efforts should therefore focus on achieving complete delivery using smaller-diameter nozzles.

Simultaneous reduction of injection volume is also likely to reduce the occurrence of deep penetration. Low-volume injections are especially attractive for immunization because they naturally target vaccines to the superficial skin layers, which have a high concentration of immune cells Furthermore, use of low-volume injections also helps in conserving vaccines, a factor that could become important during vaccine shortage.

Several additional fundamental questions need to be addressed through further research. For example, the effects of jets on skin at a cellular level are not known. This question is especially relevant in light of the proposed applications of jet injections in genetic immunization. The design of jet injectors has evolved significantly during the past decade Box 1.

The introduction of clear, plastic nozzles in DCJIs and fully disposable, pre-loaded devices are perhaps the most notable developments. However, further improvements in jet injector designs are essential to address some of the limitations of existing jet injectors.

Newer devices that offer temporal control over injection parameters such as pressure and velocity and produce consistent results despite person to person variation in skin properties are likely to improve the overall quality of injections. The earliest descriptions of jet injections date back to the nineteenth century, whereas the modern era of liquid jet injectors began in the early s.

Spring- or gas-powered devices were developed for single or multiple injection applications. Spring-powered devices have the advantages of compactness, low cost and high durability.

Their disadvantages include a limited range of force and reduced versatility. Gas-powered devices offer the advantage of sustained force generation, greater flexibility and the capacity to deliver large volumes. Their disadvantages include complexity and reliance on an exhaustible energy source Jet injectors were first popularized in the form of multi-use nozzle jet injectors MUNJIs , which were introduced in the US military between and because they offer a high rate of vaccination.

MUNJIs delivered vaccines from a single-dose vial at a rate of up to 1, per hour. The use of MUNJIs decreased drastically after evidence of contamination originating from blood and splashed liquid was uncovered.

At around the same time that MUNJIs were popularized, single-dose devices were also developed for insulin delivery. A device called the Hypospray was introduced onto the market in for insulin delivery Although Hypospray was discontinued in , other devices were introduced for single-dose administration. These injectors were non-disposable and required thorough cleaning between injections.

Disposable cartridge jet injectors DCJIs were introduced in the late s to facilitate use and cleanliness. Clear plastic nozzles that hold the drug not only facilitated cleanliness by clearly separating the drug from the actuation device but also helped in drug loading.

Today DCJIs remain the primary type of jet injectors in use. The latest form of DCJIs includes single-use, pre-filled, completely disposable injectors, which further facilitates their use and reduces risk of contamination. The jets used in commercial injectors are typically turbulent with Reynolds numbers a product of jet diameter, velocity and density divided by viscosity in the range of tens of thousands.

Pressure in the nozzle decreases gradually during skin penetration and steps down suddenly when the entire drug is ejected. The duration of injection is proportional to its volume but the overall jet properties pressure in the chamber and average jet velocity are not affected by the amount of liquid loaded in the nozzle.

The diameter of the jet is comparable to the nozzle diameter. The structure of a turbulent jet consists of two significant regions: the initial region within which the fluid travels at the exit velocity; and the main region in which the velocity decreases due to jet expansion 77 , 78 , The impact of the jet on the skin initiates hole formation in the skin and the velocity of the jet continues to decrease as it travels through the hole. Backflow of the jet is observed during hole formation if the volumetric rate of hole formation in the skin is smaller than the volumetric flow rate of the jet liquid into the skin.

Backflow from the hole further slows down the jet entering the hole and decreases the capacity of the jet to penetrate deep into the skin. Beyond a certain depth, the velocity of the jet arriving at the progressive end of the hole drops below the value necessary for hole formation. The hole depth is essentially established at this time. Stagnation pressure of further incoming jet at the end of the hole disperses fluid in a near-spherical manner around the hole.

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If you would like to know more about the types of cookies we serve and how to change your cookie settings, please read our Cookie Notice. By clicking the "I accept" button, you consent to the use of these cookies. Researchers in the Netherlands are developing laser technology to enable "virtually painless" injections without needles in what they call a breakthrough that will ease fear and lower the threshold for vaccinations. The "Bubble Gun" uses a laser to push tiny droplets through the outer layer of the skin, said David Fernandez Rivas, a professor at Twente University and research affiliate at the Massachusetts Institute of Technology who founded the idea.

The process is quicker than a mosquito bite and "should not cause pain" because nerve endings in the skin are not touched, he said, adding this would be studied further.

Rivas expects the invention will not only help more people get vaccinated, but will also prevent the risk of contamination by dirty needles and reduce medical waste. Testing on tissue samples has successfully been carried out with a 1. An application for funding to begin human testing with volunteers is expected to be submitted this month, Rivas said.

A new start-up company will collaborate with the pharmaceutical industry to test and market the "Bubble Gun" technology, he said. It could however take years for the method to be available to the general public, depending on the progress of research and regulatory issues.

Roughly one in five Dutch people are afraid of needles, said Henk Schenk, who offers therapy to help those suffering acutely. People are ashamed to admit it. Some people trace their fears back to a traumatic childhood hospital admission, or are afraid of surrendering control. A small number of roughly 1 out of 1, have a deep phobia that requires repeated sessions to prepare them for a jab. Yet globally, young people have the worst access to youth mental health care within the lifespan and across all the stages of illness particularly during the early stages.

In response, the Forum has launched a global dialogue series to discuss the ideas, tools and architecture in which public and private stakeholders can build an ecosystem for health promotion and disease management on mental health.