Department of Pharmaceutics and Pharmaceutical Nanotechnology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Sensors and Integrated Bio-MEMS/Microfluidics Laboratory, School of Mechanical Engineering, Iran University of Science and Technology, Tehran, Iran.
Drug Deliv Transl Res. 2024 Feb;14(2):386-399. doi: 10.1007/s13346-023-01406-8. Epub 2023 Aug 14.
Most topical drug delivery techniques do not provide therapeutic concentrations for treatment of surgical site and other local infections and, therefore, require some kind of enhancement, such as physical methods like microneedles, the subject of the present investigation. Here, controlled-release long-lasting antibacterial polylactic acid (PLA) microneedles containing 1, 3, and 5% silver nanoparticles (AgNP) were prepared using micro-molding solvent-casting technique. Microneedles were characterized using optical microscopy, SEM, FTIR, XRD, and DSC. Also, mechanical strength, barrier disruption ability, insertion depth, in-vitro release kinetics, antibacterial activity against Staphylococcus aureus and Pseudomonas aeruginosa, and silver permeation through rat skin were studied. Microneedles showed good mechanical strength with no signs of failure at an optimum PLA concentration of 25% (w/v). FTIR revealed no chemical interaction between ingredients, and XRD confirmed presence of AgNP in microneedles. Microneedles penetrated the skin model at depth of up to 1143 μm resulting 5-7 times increase in transepidermal water loss (TEWL). Release studies showed 2.2, 6.8, and 8.1 µg silver release from the whole body (obeying Higuchi's release model) and 0.33, 0.45, and 0.78 µg from the needles alone (obeying Fickian-cylindrical type release) for 1, 3, and 5% AgNP microneedles, respectively. Also, prolonged antibacterial activity (for 34 days) was observed. Skin studies over 72 h indicated that besides needles, silver is also released from the baseplate which had a marginal share in total silver permeation through the skin. In conclusion, a straightforward solvent-casting technique can be used to successfully prepare strong AgNP-containing PLA microneedles capable of long-lasting antibacterial activity.
大多数局部药物递送技术无法为手术部位和其他局部感染提供治疗浓度，因此需要某种增强，例如微针等物理方法，这是本研究的主题。在这里，使用微成型溶剂浇铸技术制备了含有 1%、3%和 5%载银纳米粒子（AgNP）的控释长效抗菌聚乳酸（PLA）微针。使用光学显微镜、SEM、FTIR、XRD 和 DSC 对微针进行了表征。还研究了机械强度、破坏屏障能力、插入深度、体外释放动力学、对金黄色葡萄球菌和铜绿假单胞菌的抗菌活性以及银通过大鼠皮肤的渗透。在最佳 PLA 浓度为 25%（w/v）时，微针表现出良好的机械强度，没有失效迹象。FTIR 显示成分之间没有化学相互作用，XRD 证实了 AgNP 存在于微针中。微针可穿透皮肤模型的深度达 1143μm，导致经皮水分损失（TEWL）增加 5-7 倍。释放研究表明，1%、3%和 5%AgNP 微针从整体（符合 Higuchi 释放模型）释放 2.2、6.8 和 8.1µg 银，从针体单独释放 0.33、0.45 和 0.78µg 银（符合菲克型圆柱型释放）。还观察到了延长的抗菌活性（34 天）。72 小时的皮肤研究表明，除了针体之外，银还从基底片中释放出来，基底片在银通过皮肤的总渗透中仅占很小的份额。总之，简单的溶剂浇铸技术可用于成功制备具有长效抗菌活性的强载银 PLA 微针。
