A Novel Transdermal Protein Delivery Strategy via Electrohydrodynamic Coating of PLGA Microparticles onto Microneedles
A Novel Transdermal Protein Delivery Strategy via Electrohydrodynamic Coating of PLGA Microparticles onto Microneedles
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DOI：
10.1021/acsami.9b22425
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发表时间：
2020-03-18
影响因子：
9.5
通讯作者：
Williams, Gareth R.
中科院分区：
文献类型：
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作者：
Angkawinitwong, Ukrit;Courtenay, Aaron J.;Williams, Gareth R.
生物治疗药物的透皮递送正在成为静脉或皮下注射的有效替代方案。后者面临着重大挑战，包括患者不适、需要训练有素的人员、专门的锐器处理和感染风险。微针 (MN) 技术克服了上述许多挑战，将生物材料直接输送到皮肤中，并允许在动物模型和人体中持续释放活性成分。本研究描述了使用电流体动力雾化 (EHDA) 将负载卵清蛋白 (OVA) 的 PLGA 纳米颗粒涂覆到形成水凝胶的 MN 阵列上。这些颗粒显示出 OVA 的延长释放超过约 100 小时。 28天。显微镜分析表明，EHDA 可以在 MN 上生成均匀的颗粒涂层，涂层效率为 30%。此外，涂层纳米阵列表现出与未涂层系统相似的机械特性和插入特性，这表明涂层对纳米阵列的应用不会产生有害影响。与未处理的小鼠相比，包被的 MN 导致 C57BL/6 小鼠体内抗 OVA 特异性 IgG 滴度没有显着增加（配对 t 检验，p > 0.05），表明该制剂是非免疫原性的。因此，使用 EHDA 涂覆 MN 阵列的方法似乎具有作为一种新型非侵入性蛋白质递送策略的潜力。
Transdermal delivery of biological therapeutics is emerging as a potent alternative to intravenous or subcutaneous injections. The latter possess major challenges including patient discomfort, the necessity for trained personnel, specialized sharps disposal, and risk of infection. The microneedle (MN) technology circumvents many of the abovementioned challenges, delivering biological materials directly into the skin and allowing sustained release of the active ingredient both in animal models and in humans. This study describes the use of electrohydrodynamic atomization (EHDA) to coat ovalbumin (OVA)-loaded PLGA nanoparticles onto hydrogel-forming MN arrays. The particles showed extended release of OVA over ca. 28 days. Microscopic analysis demonstrated that EHDA could generate a uniform particle coating on the MNs, with 30% coating efficiency. Furthermore, the coated MN array manifested similar mechanical characteristics and insertion properties to the uncoated system, suggesting that the coating should have no detrimental effects on the application of the MNs. The coated MNs resulted in no significant increase in anti-OVA-specific IgG titres in C57BL/6 mice in vivo as compared to the untreated mice (paired t-test, p > 0.05), indicating that the formulations are nonimmunogenic. The approach of using EHDA to coat an MN array thus appears to have potential as a novel noninvasive protein delivery strategy.