Department of NanoEngineering, ‡Moores Cancer Center, University of California, San Diego , La Jolla, California 92093, United States.
Langmuir. 2013 Oct 1;29(39):12228-33. doi: 10.1021/la402695c. Epub 2013 Sep 16.
We report a novel pH-responsive gold nanoparticle-stabilized liposome system for gastric antimicrobial delivery. By adsorbing small chitosan-modified gold nanoparticles (diameter ~10 nm) onto the outer surface of negatively charged phospholipid liposomes (diameter ~75 nm), we show that at gastric pH the liposomes have excellent stability with limited fusion ability and negligible cargo releases. However, when the stabilized liposomes are present in an environment with neutral pH, the gold stabilizers detach from the liposomes, resulting in free liposomes that can actively fuse with bacterial membranes. Using Helicobacter pylori as a model bacterium and doxycycline as a model antibiotic, we demonstrate such pH-responsive fusion activity and drug release profile of the nanoparticle-stabilized liposomes. Particularly, at neutral pH the gold nanoparticles detach, and thus the doxycycline-loaded liposomes rapidly fuse with bacteria and cause superior bactericidal efficacy as compared to the free doxycycline counterpart. Our results suggest that the reported liposome system holds a substantial potential for gastric drug delivery; it remains inactive (stable) in the stomach lumen but actively interacts with bacteria once it reaches the mucus layer of the stomach where the bacteria may reside.
我们报告了一种新型的 pH 响应金纳米粒子稳定脂质体系统，用于胃内抗菌药物传递。通过将小的壳聚糖修饰的金纳米粒子（直径约 10nm）吸附到带负电荷的磷脂脂质体（直径约 75nm）的外表面上，我们发现脂质体在胃 pH 条件下具有极好的稳定性，融合能力有限，货物释放可忽略不计。然而，当稳定的脂质体存在中性 pH 的环境中时，金稳定剂从脂质体上脱离，导致游离脂质体能够主动与细菌膜融合。我们使用幽门螺杆菌作为模型细菌和强力霉素作为模型抗生素，证明了纳米粒子稳定的脂质体具有这种 pH 响应的融合活性和药物释放特性。特别是，在中性 pH 下，金纳米粒子脱离，因此负载强力霉素的脂质体迅速与细菌融合，并导致比游离强力霉素更好的杀菌效果。我们的结果表明，所报道的脂质体系统在胃内药物传递方面具有很大的潜力；它在胃腔中保持不活跃（稳定），但一旦到达可能存在细菌的胃黏液层，它就会与细菌积极相互作用。
