8.4.1.3　The third generation：minimally invasive TD...

The third generation of TDD technology promotes the delivery of drugs by microchannels on the epidermis formed by minimally invasive，such as the destruction of the stratum corneum by radio frequency ablation，ultrasound，and laser to form microchannels.Since the size of the formed microchannels is much larger than the size of the drug molecules，various hydrophilic and hydrophobic drugs，proteins，DNAs and other large molecular biologicals can effectively pass.However，these transdermal administration approaches often rely on bulky and expensive equipments and technical personnel to operate，as well as causing some pain to patients.Hopefully，in recent years，the rise of microneedles（MNs）has thrown new light on the TDD field.MNs are matrix arrays formed by micrometer-level small needles，which include solid MNs，hollow MNs，coated MNs，soluble MNs，swellable MNs（also known as hydrogel MNs or phase-transition MNs），etc.MNs are generally 50-1000μm long，which is often hard to reach the dermal nerve，so the pain is often mild.As a novel drug delivery approach，microneedle array has advantages of painlessness，accurate positioning，minimally invasive，safe and efficient，easy to carry，and patients can use it by themselves.MNs are especially suitable for the administration of biologicals（e.g.，macromolecules，nucleic acids，peptides，proteins，vaccines），and have become the most potential minimally invasive drug delivery method in the third generation of TDD technology.Although the third generation of TDD technology can transiently damage the skin barrier，the damage will be quickly repaired by self.(https://www.daowen.com)