Microneedles could expand transdermal delivery of drugs

The microneedle approach could make delivery across the skin feasible for a much wider range of drugs than at present, and could even confer some safety advantages, according to the researchers. In the landmark trial, reported in the current edition of journal Proceedings of the National Academy of Sciences, a research team was able to deliver detectable concentrations of the skin-impermeant mu-opioid receptor antagonist naltrexone to volunteers using a microneedle-coated transdermal patch, without any skin pre-treatment. The rationale behind microneedle-based drug delivery is that such technology will reduce the need for hypodermic injections, which can be painful and usually need to be administered by a trained professional. These issues aside, combining the technology with more established transdermal delivery mechanisms may help overcome some of the shortcomings of the latter technique. For example, while the transdermal administration has been employed in indications ranging from pain management to hormone replacement, to date the approach has been limited to the delivery of drugs that can readily pass through the skin. The study, conducted by Daniel Wermeling of​ the Department of Pharmacy Practice and Science at UK's College of Pharmacy in collaboration with colleagues at the Georgia Institute of Technology in the USA, was designed to see if combining microneedle and transdermal techniques could improve drug delivery. The team applied thumb-sized patches containing 50 stainless steel microneedles, of around 620 microns in length, to the arms of six healthy volunteers, before coating the area with a gel containing the drug under examination, the anti-addiction product naltrexone, to the affected area. The blood stream concentration of the drug in the subjects, and comparable control group who had not had microneedles applied, was monitored for a 72-hour period. The team found that pharmacologically-active levels of naltrexone were detectable in the microneedle group very rapidly after administration, whereas no member of the placebo group demonstrated measurable levels. Furthermore, the concentration of detectable naltrexone remained stable for 48 hours post administration, indicating that the pores created by the microneedles began to heal and no longer allow entry of the drug after this time. This effect was subsequently confirmed using electrical resistance testing. Aside from the potential advantages in ease of administration that the results indicate, the researchers suggested that microneedle techniques offer benefits in terms of the creation of secondary metabolites. Dr Wermeling explained that, when administered orally, naltrexone is broken-down by the liver to produce naltrexol, which circulates for an extended period resulting in undesirable side effects. He went on to say that, while naltrexol had been observed during the microneedle study, it was seen at a significantly reduced concentration. Dr Wermeling concluded that, "during the first week of treatment using oral naltrexone, 10 to 20 per cent of patients drop out of treatment because of side effects​," adding "if you can change the way the parent drug is presented in a way that affects how the metabolites are formed, you could improve the safety or side effects of the drug​."