Efficient delivery of nanoparticles to deep skin layers using dissolvable microneedles with an extended-length design

Skin pretreatment with microneedles (MNs) increases drug permeation through the skin by creating microchannels in the skin. However, because of skin's inherent elasticity and self-healing ability, these microchannels shrink or reseal rapidly, thus limiting the nanoparticle (NP) delivery efficiency. This study reports dissolvable polyvinyl alcohol/polyvinylpyrrolidone (PVA/PVP) MNs with an extended-length design for the efficient transdermal delivery of NPs. In this system, poly(D,L-lactide-co-glycolide) NPs are encapsulated within the pyramidal structure of the MNs. The extended length of the PVA/PVP MN allows it to counteract skin indentation during insertion, thus enabling complete insertion of the pyramidal structure into the skin to deliver the NPs. In contrast to MN pretreatments that require passive diffusion of NPs through the skin, the extended PVA/PVP MNs can directly bring the NPs into the deeper skin layers, and then rapidly dissolve in 3 min to release the payload. An in vivo transdermal delivery study showed that approximately 90% of the loaded NPs were delivered to the viable epidermis and dermis, whereas only < 2% of topically applied NPs were detected in the skin after being treated with a commercial 3M(TM) MN product. The NPs delivered by the extended MN remained at the insertion site for 5 days, enabling a sustained release of active agents to the diseased tissue. The proposed MN system could be a promising tool for the transdermal delivery of NPs to treat deep skin diseases such as bacterial infections and malignant tumors.