Successful delivery of a DNA vaccine to antigen-presenting cells and their subsequent stimulation of CD4⁺ and CD8⁺ T cell immunity remains an inefficient process. In general, the delivery of prophylactic vaccines is mainly mired by low transfection efficacy, poor immunogenicity, and safety issues from the materials employed. Currently, several strategies have been exploited to improve immunogenicity, but an effective strategy for safe and pain-free delivery of DNA vaccines is complicated. Herein, we report the rapid delivery of polyplex-based DNA vaccines using microneedle arrays coated with a polyelectrolyte multilayer assembly of charge reversal pH-responsive copolymer and heparin. The charge reversal pH-responsive copolymer, composed of oligo(sulfamethazine)-b-poly(ethylene glycol)-b-poly(amino urethane) (OSM-b-PEG-b-PAEU), was used as a triggering layer in the polyelectrolyte multilayer assembly on microneedles. Charge reversal characteristics of this copolymer, that is, the OSM-b-PEG-b-PAEU copolymer exhibit, positive charge at low pH (pH 4.03) and becoming negative charge when exposed to physiological pH conditions (pH 7.4), allowing the facile assembly and disassembly of polyelectrolyte multilayers. The electrostatic repulsion between heparin and OSM-b-PEG-b-PAEU charge reversal copolymer triggered the release of DNA vaccines. DNA vaccines laden on microneedles are effectively transfected into RAW 264.7 macrophage cells in vitro. Vaccination of BALB/c mice by DNA vaccine-loaded microneedle arrays coated with a polyelectrolyte multilayer generated antigen-specific robust immune responses. These findings provide potential strategy of charge reversal pH-responsive copolymers coated microneedles for DNA vaccine delivery.

将DNA疫苗成功递送至抗原呈递细胞并随后刺激CD4 ⁺和CD8 ⁺ T细胞免疫仍然是效率低下的过程。通常，预防性疫苗的递送主要被转染功效低，免疫原性差和所用材料的安全性问题所困扰。当前，已经开发了几种策略来改善免疫原性，但是用于安全无痛地递送DNA疫苗的有效策略是复杂的。本文中，我们报道了使用微针阵列快速涂覆基于多聚体的DNA疫苗，该微针阵列涂有电荷逆转pH响应共聚物和肝素的聚电解质多层组装体。电荷反转的pH响应共聚物，由低聚（磺胺二甲嘧啶）-b组成-聚（乙二醇）-b-聚氨基氨基甲酸酯（OSM- b- PEG- b- PAEU）被用作微针上的聚电解质多层组件中的触发层。该共聚物的电荷反转特性，即OSM- b -PEG- b -PAEU共聚物在低pH值（pH 4.03）下表现出正电荷，而在生理pH条件（pH 7.4）下则变成负电荷，因此很容易聚电解质多层的组装和拆卸。肝素和OSM-之间的静电斥力b -PEG- b-PAEU电荷逆转共聚物触发了DNA疫苗的释放。载于微针上的DNA疫苗可在体外有效转染到RAW 264.7巨噬细胞中。用涂有聚电解质多层膜的DNA疫苗加载的微针阵列对BALB / c小鼠进行疫苗接种可产生抗原特异性的强大免疫反应。这些发现提供了用于DNA疫苗递送的电荷逆转pH响应共聚物包被的微针的潜在策略。