Laboratory of Polymer Chemistry and Technology, Department of Chemistry, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece.
Laboratory of Pharmaceutical Technology, Division of Pharmaceutical Technology, School of Pharmacy, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece.
Molecules. 2024 Sep 10;29(18):4289. doi: 10.3390/molecules29184289.
Current transdermal drug delivery technologies, like patches and ointments, effectively deliver low molecular weight drugs through the skin. However, delivering larger, hydrophilic drugs and macromolecules remains a challenge. In the present study, we developed novel transdermal nanoneedle patches containing levofloxacin-loaded modified chitosan nanoparticles. Chitosan was chemically modified with transcutol in three ratios (1/1, 1/2, 1/3, /), and the optimum ratio was used for nanoparticle fabrication via the ionic gelation method. The successful modification was confirmed using ATR-FTIR spectroscopy, while DLS results revealed that only the 1/3 ratio afforded suitably sized particles of 220 nm. After drug encapsulation, the particle size increased to 435 nm, and the final formulations were examined via XRD and an in vitro dissolution test, which suggested that the nanoparticles reach 60% release in a monophasic pattern at 380 h. We then prepared transdermal patches with pyramidal geometry nanoneedles using different poly(lactic acid)/poly(ethylene adipate) (PLA/PEAd) polymer blends of varying ratios, which were characterized in terms of morphology and mechanical compressive strength. The 90/10 blend exhibited the best mechanical properties and was selected for further testing. Ex vivo permeation studies proved that the nanoneedle patches containing drug-loaded nanoparticles achieved the highest levofloxacin permeation (88.1%).
目前的经皮药物传递技术，如贴片和软膏，可有效地通过皮肤传递低分子量药物。然而，传递更大、亲水性药物和大分子仍然是一个挑战。在本研究中，我们开发了含有左氧氟沙星负载改性壳聚糖纳米颗粒的新型经皮纳米针贴片。壳聚糖通过化学方法用 transcutol 修饰，修饰比为 1/1、1/2、1/3（/），并使用离子凝胶法制备最佳比例的纳米颗粒。ATR-FTIR 光谱证实了成功的修饰，而 DLS 结果表明只有 1/3 的比例才能提供合适大小的 220nm 颗粒。药物包封后，粒径增加到 435nm，最终制剂通过 XRD 和体外溶出度试验进行了检查，表明纳米颗粒在 380h 内以单相模式达到 60%的释放。然后，我们使用不同比例的聚乳酸/聚己二酸丁二醇酯（PLA/PEAd）聚合物混合物制备了具有金字塔形几何形状的纳米针经皮贴片，并对其形貌和机械压缩强度进行了表征。90/10 混合物表现出最佳的机械性能，并被选择用于进一步测试。体外渗透研究证明，载药纳米颗粒的纳米针贴片实现了最高的左氧氟沙星渗透（88.1%）。
