In a bid to confront the under-use of current needle-free methods driven by the pain and discomfort experienced by patients, a team of researchers based at University of California has developed an alternative, painless, needle-free drug delivery system in collaboration with drug delivery company StratGent Life Sciences. The new injectors promise to potentially deliver macromolecules such as vaccines and protein therapeutics painlessly without the use of a needle, thus increasing patient comfort and compliance, as well as removing the risk of needle-stick injuries to healthcare workers. Guided by the hypothesis that the cause of the pain and bruising from standard needle-free liquid jet injectors was the result of deep penetration of the jets of the drug into the skin, the team developed a novel injector system that minimises the depth of penetration by using pulsed micro-jets at very high speeds and very small volumes. "The device consists of a chamber that holds the drug solution," Dr Samir Mitragotri, lead author of the research paper on the new technique that was published in the Proceedings of the National Academy of Sciences, told In-PharmaTechnologist.com. "The chamber is connected to a nozzle that has a final diameter of about 50-100 micrometers. The chamber is fitted with a piston which is backed up by a piezoelectric crystal, and when a voltage pulse is applied to the crystal it moves forward and pushes the piston. This, in turn, pushes the drug in the form of a small jet which penetrates into the skin." The pulsed micro-jets are expelled at over 100 metres per second at volumes of just 2-15 nanolitres per pulse. The number of pulses can be varied according to the required drug dose, and can be delivered in quick succession to mimic a standard injection, or delivered slowly over a period of time in a similar fashion to a conventional transdermal delivery system. The device could also be developed to incorporate multiple nozzles to facilitate higher doses. Using insulin as a model drug for in vivo experiments with rats, the research team was able to demonstrate systemic delivery of macromolecules using their novel micro-jet injector. Although it takes a little longer for the drug treatment to reach the bloodstream using this delivery system compared to conventional injections, the team established bioequivalence of the two methods with absolutely no adverse side effects using the new technique in contrast to the bleeding and bruising observed with traditional jet injectors. Further research is needed to determine whether any kind of reformulation of current drugs would be required in order for them to be delivered via this new method, but the ultimate aim of the research group is to establish a technology platform that could be used for the delivery of a variety of vaccines and biotech drugs. "The pulsed micro-jets…open up new possibilities in needle-free delivery of macromolecular drugs," say the researchers. "Compared with hypodermic needles, they offer a needle-free and patient-compliant mode of drug administration. Compared with passive transdermal patches, they allow delivery of macromolecules, provide rapid onset, and controlled, programmable, and precise dosing." According to the team, the devices could potentially have many applications, including systemic, programmable delivery of drugs (such as insulin for diabetes or fentanyl for pain management), delivery of small doses in superficial layers for use with vaccines, or precise local delivery into the skin which could be used for the treatment of acne or cold sores. Further development is underway to bring the product to a stage where it is ready for the market, and it is too early to accurately estimate the final cost of the novel drug delivery system, said Mitragotri. However, US drug delivery firm StrataGent Life Sciences has been involved with the research to date and is leading commercial development of the new technology. With around 12 billion needle injections every year for the delivery of vaccines and protein therapeutics such as insulin, growth hormones and erythropoietin, the novel micro-jet injection devices open up another option in the rapidly expanding needle-free injection market, set to hit $3bn (€2.3bn) by 2010.