Enhanced Transdermal Drug Delivery Through Development Of Pillar-Based Dissolving Microneedle
Oral and parenteral injections are among the widely used drug delivery routes. While oral drug delivery is remarkably more patient-friendly compared with injection, it is associated with a number of side effects including vomiting, headache, abdominal pain, diarrhea and nausea. Furthermore, the bioavailability of a large number of drugs is reduced due to first-pass elimination of body. On the other hand, hypodermic injection is advantageous compared with oral delivery as it delivers drugs directly into the blood stream, reducing side effects due to accurate dosage delivery. However, hypodermic injection is also associated with various drawbacks including requirement of expertise to administer an injection, and the potential of infections caused by needle stick waste. Therefore, to solve above mentioned limitations, dissolving microneedles (DMNs) were developed.
DMNs are polymeric micro-sized needles capable of loading drugs within their body and releasing them upon application for systemic or local delivery. This is an interesting transdermal drug delivery platform, as it has proven to be capable of delivering a wide range of drugs including unstable drugs and even vaccines. As DMNs are much smaller than traditional hypodermic needles, they are considered minimally invasive and are less likely to cause pain upon application making them a patient-friendly approach to therapeutic administration. On the other hand, DMNs are mainly places onto patches, which often reduces the delivery efficacy of encapsulated materials because of skin elasticity. In addition, the chemicals in the patch may cause skin irritation. Moreover, it is difficult to adhere patches to flexible body joint areas and to hairy skin. Especially, patients must wait for long time for the DMNs to completely dissolve before the patch can be removed.
Lately, diverse researches have been developed to overcome the limitations of transdermal drug delivery with DMNs. Troy microneedle, combination with metal and polymer DMN has been developed to conduct complete insertion of DMNs into the skin. Two-layered DMNs and arrowhead DMNs have been fabricated to deliver drug which is composed of polymer layer and drug encapsulated needles with greater efficiency. Although these developments could improve the general delivery efficacy of DMNs, the fundamental problems which can cause skin damage or pain associated with incomplete insertion of DMN patch systems have not been fully addressed yet. Also, a patchless Microlancer has been introduced, which is an innovative applicator capable of inserting drug encapsulated DMNs without patch. This study has found a solution to fully insert DMNs.
n this study, to solve limitations associated with DMN transdermal drug delivery, we have developed patch-less micro pillars, capable of inserting DMNs into skin within less than a minute in a minimally invasive manner. We have optimized pillars with a height of 300 μm with a base diameter of 500 μm, resulting in a safe application reducing skin pain without penetration of micro pillars into the skin. Through a series of in vitro and in vivo experiments, we show that pillar-based DMN (P-DMN)s are capable of delivering encapsulated materials with a significantly higher efficiency than traditional DMN patches at a remarkably faster rate.
Unlike traditional DMN patches, P-DMNs can be effectively applied to hairy parts of body and movable joints. P-DMNs are simple and economical to fabricate and mass-produce, thus suggesting a high potential to replace traditional DMN patches in future.
