8.6　Challenges and Perspectives

At present，the first and second generations of transdermal drug delivery technology have been widely used in clinical practice，but the efficiency is generally low and it is difficult to meet the requirements of transdermal drug delivery of macromolecules such as biologicals.The third generation of transdermal drug delivery technology promotes drug delivery through minimally invasive microchannels formed on the epidermis，and is suitable for most drugs，including biologicals.However，most of the third generation of transdermal drug delivery technologies rely on cumbersome and expensive equipments and the operation of professional technicians，thus microneedles have become the most potential minimally invasive drug delivery methods in the third generation of transdermal drug delivery due to its simple medication method and wide applicability.

Although microneedles based on biomedical polymers have developed rapidly in recent years，there are currently no approved polymer microneedle products，with only one application study of polymer microneedles（hyaluronic acid soluble microneedles for the study of plaque psoriasis（NCT02955576））in skin diseases entering the clinical trail stage.In contrast，the hollow microneedles influenza vaccine Intanza®was approved by the US FDA as early as 2009，and various types of vaccines based on hollow microneedles have entered phase Ⅱ or phase Ⅲ of clinical trial as well.

While polymer microneedles have numerous advantages，they are not without shortcomings，such as polymer deposition in the skin，low mass production efficiency，low product reproducibility（uneven residue，uneven drug loading），and high production costs.In addition，even if studies have shown that microneedles can be made larger in a simple way without troubling patients using by self，low drug loading is still a major challenge which hinders the clinical application of polymer microneedles.(https://www.daowen.com)

In addition，many studies remain at the cell level in vitro and even at the level of skin simulant，and many mechanisms are difficult to verify intuitively at the animal level due to the limitations of animal models even if there are more than 3000 kinds of skin diseases to be deeply studied.Furthermore，recent studies have shown that drugs will reside in the lymph nodes，liver，kidneys，and spleen after microneedle administration，which need further research on the pharmacokinetics and safety of microneedle administration.In conclusion，the research on the application of polymer microneedles in skin diseases is still a daunting task and has a long way to go.

The fourth generation of transdermal drug delivery technology based on controlled and feedback-guided intelligent device is still in the early stage of development，but it is reasonable to expect that the combination of polymer microneedles and intelligent device will open a new chapter of transdermal drug delivery.