Microneedles: Physical enhancers for (trans)dermal drug delivery

Abstract

The efficiency of(trans)dermal drug delivery has been severely reduced by the inability of most drugs to penetrate the skin at therapeutically useful rates. Recently, the use of micron-scale needles has been shown to increase skin permeability and significantly improve (trans)dermal drug delivery, particularly for macromolecules. Using the tools of the microelectronics industry and different materials, microneedles of various sizes and shapes have been fabricated. Due to their micron size (less than 300 μm in diameter and 50-900 μm in length), these needles do not reach the nerve endings in the dermis, providing a painless application, which is considered as their main advantage over hypodermic needles. Pathways created using microneedles are orders of magnitude bigger than molecular dimensions and, therefore, should readily permit transport of macromolecules, as well as possibly supramolecular complexes and microparticles Recently, in vivo studies have demonstrated a successful delivery of oligonucleotides, insulin, and many other drugs using a microneedles, as well as induction of the immune response from protein and DNA vaccines. Numerous studies conducted in this research field have led to launching the first microneedle-based (trans)dermal drug delivery systems on the market.

Efikasnost terapijskih sistema za (trans)dermalnu isporuku lijekova je u znatnoj mjeri umanjena zbog otežanog prolaska lijekova u/kroz kožu. Nedavno je pokazano da je upotrebom igala mikronskih veličina moguće povećati permeabilnost kože i znatno poboljšati (trans)dermalnu isporuku, naročito u slučaju makromolekula. Primjenom dostignuća mikroelektronske industrije, od različitih materijala su proizvedene mikroigle različitih veličina i oblika. S obzirom na svoje mikronske veličine (prečnika obično oko 1 μm i dužine 50-900 μm), ovakve igle ne dopiru do nervnih završetaka u dermisu, čime obezbjeđuju bezbolnu primjenu, što se smatra njihovom osnovnom prednošću u odnosu na potkožne igle. Nastale pore u koži su nekoliko puta veće od dimenzija molekula, te je omogućen transport makromolekula, kao i supramolekularnih kompleksa i nano/mikročestica. Dosadašnje in vivo studije su pokazale uspješnu (trans)dermalnu isporuku oligonukleotida, insulina i drugih lijekova primjenom mikroigala, kao i indukciju imunskog odgovora proteinskim i DNK vakcinama. Brojni radovi sprovedeni u ovoj oblasti istraživanja doveli su i do pojave na tržištu prvih sistema za (trans)dermalnu isporuku lijekova zasnovanih na tehnologiji mikroigala.