**3.1 Microneedle**

Microneedle technology uses small needles, which creates small pores in the skin, allowing the protein or peptide to cross the outermost physical barrier [109]. Since one goal of transdermal delivery is to increase efficacy while still retaining an easy, noninvasive technique, microneedles are designed to breach only the stratum corneum [110]. Since the microneedles do not reach the viable dermis, both the capillaries and the nerve ends are avoided. Thus, this approach leads to painless feelings during the drug delivery. These needles have been made using various materials, including silicon, different metals, and biodegradable material such as polymers or sugars [111].

Different types of microneedles, as well as drug introduction routes, have been tested for efficient delivery of protein or peptide therapeutics [112]. In one method, needles are used to puncture the skin to create pores, followed by the drug administration. Another method involves coating the microneedle with the protein or peptide of interest. Thus, the creation of pores by the microneedles will allow the drug to enter the body. Another method involves encapsulating the drug in biodegradable microneedles. In this method, the drug will be released slowly as the microneedles degrade. Another method utilizes hollow microneedles, through which the therapeutic protein or peptide can be infused following the puncture of the skin.
