微针(MNs)技术已经在经皮药物递送中进行了20多年的研究,并进行了数百次临床试验。然而,由于材料安全方面的挑战,目前在医学上没有市售的MN,具有成本效益的制造,和大规模制造。在这里,首次提出了一种基于红外辐照工艺的水凝胶微针的快速绿色制造方法。优化配方为聚乙烯醇(PVA)和聚乙烯吡咯烷酮(PVP),作为交联材料和成孔剂,分别。制造方法包括将MNs贴片在70°C的红外辐射下放置2分钟,然后退火以获得具有优异溶胀行为的HMNs,机械强度,和生物相容性。当模型药物壬二酸(AZA)和苦参碱(MAT)加载到HMNs系统中时,MAT的化学稳定性明显提高。离体透皮给药实验表明,HMNs可以实现AZA和MAT的同步释放,两种药物的24小时经皮通透性分别为73.09±0.48%和71.56±1.23%,分别。体内药代动力学研究,HMNs给药呈现两种药物的剂量依赖性稳定的血药浓度。此外,在药效学评价中,载药HMNs组有显著的抗肿瘤疗效和生物安全性.总之,高效的,方便,基于红外辐射的低成本制造方法为大量生产载药HMN提供了可能性,显示出工业制造业发展的潜力。
Microneedles (MNs) technology has been studied in transdermal drug delivery for more than 20 years with hundreds of clinical trials conducted. However, there are currently no commercially available MNs in medicine due to challenges in materials safety, cost-effective fabrication, and large-scale manufacturing. Herein, an approach for rapid and green fabrication of hydrogel microneedles (HMNs) based on infrared irradiation process was proposed for the first time. The optimized formulation consisted of polyvinyl alcohol (PVA) and polyvinyl pyrrolidone (PVP), which acted as cross-linked materials and pore-forming agents, respectively. The manufacturing method involved placing MNs patches under infrared irradiation at 70 °C for 2 min and annealing to obtain HMNs with excellent swelling behavior, mechanical strength, and biocompatibility. When model drugs azelaic acid (AZA) and matrine (MAT) were loaded into HMNs systems, the chemical stability of MAT was significantly improved. Ex vivo transdermal delivery experiments indicated that HMNs could achieve synchronous release of AZA and MAT, and the 24-hour percutaneous permeability rates of both drugs were 73.09 ± 0.48 % and 71.56 ± 1.23 %, respectively. In-vivo pharmacokinetic studies, HMNs administration presented dose-dependent stable blood drug concentrations for both drugs. Additionally, prominent anti-tumor efficacy and biosecurity were observed in the drug-loaded HMNs group in the pharmacodynamic evaluation. In summary, the efficient, convenient, and low-cost fabrication method based on infrared irradiation offers the possibility of mass production of drug-loaded HMNs, showing potential for industrial manufacturing development.