Synthetic Charge-Invertible Polymer for Rapid and Complete Implantation of Layer-by-Layer Microneedle Drug Films for Enhanced Transdermal Vaccination

Abstract

<p class="first" id="P3">The utility of layer-by-layer (LbL) coated microneedle (MN) skin patches for transdermal drug delivery has been proven a promising approach, with advantages over hypodermal injection due to painless and easy self-administration. However, the long epidermal application time required for drug implantation by existing LbL MN strategies (15 to 90 minutes) can lead to potential medication noncompliance. Here, we developed a MN platform to shorten the application time in MN therapies based on a synthetic pH-induced charge-invertible polymer poly(2-(diisopropylamino) ethyl methacrylate- <i>b</i>-methacrylic acid) (PDM), requiring only 1-minute skin insertion time to implant LbL films <i>in vivo</i>. Following MN-mediated delivery of 0.5 μg model antigen chicken ovalbumin (OVA) in the skin of mice, this system achieved sustained release over 3 days and led to an elevated immune response as demonstrated by significantly higher humoral immunity compared with OVA administration <i>via</i> conventional routes (subcutaneously and intramuscularly). Moreover, in an <i>ex vivo</i> experiment on human skin, we achieved efficient immune activation through MN-delivered LbL films, demonstrated by a rapid uptake of vaccine adjuvants by the antigen presenting cells. These features—rapid administration and the ability to elicit a robust immune response—can potentially enable a broad application of microneedle-based vaccination technologies. </p><p id="P4"> <div class="figure-container so-text-align-c"> <img alt="" class="figure" src="/document_file/d9739bbb-d37c-4a36-9161-dc2fc1cd0059/PubMedCentral/image/nihms-1024404-f0001.jpg"/> </div> </p>