WRCBB, Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Powai, Mumbai 400076, India.
Integr Biol (Camb). 2013 Jan;5(1):239-48. doi: 10.1039/c2ib20122d.
The present study focuses on the development of multi-trigger responsive surface active lipid nanovesicles encapsulating paclitaxel with the hypothesis that pulmonary surfactant mimetic lipid vesicles sensitive to temperature and enzyme simultaneously will offer synergistic advantage towards improved therapeutic efficacy of paclitaxel via aerosol administration. The nanovesicles showed a unimodal size distribution of the particles (100-150 nm) and high encapsulation efficiency of paclitaxel (82%). Triggered release of paclitaxel was observed at ∼42 °C in the presence of secretory phospholipase A(2) enzyme with maximum release observed with both the triggers used simultaneously. Since these nanovesicles are intended for aerosol administration in the treatment of lung cancer, they were engineered to have high surface activity and airway patency, in order to mimic pulmonary surfactant functions. High deposition of nanovesicles in the lower impingement chamber of a twin impinger upon nebulization suggested them to be capable of reaching the terminal regions of the lungs. Nanovesicles showed facilitated and ATP dependent active uptake by A549 cells. The cytotoxic potential of the nanovesicles was significantly increased upon simultaneous use of both the triggers with an IC(50) of 49.3 nM. Overall, these studies suggest the therapeutic potential and advantages of multi trigger responsive lipid nanovesicles with encapsulated paclitaxel over that of the commercially available form of paclitaxel namely Taxol, and suggests the feasibility of aerosol administration in the treatment of lung cancer and pulmonary metastasis.
本研究专注于开发多触发响应性表面活性脂质纳米囊泡，包载紫杉醇，假设对温度和酶同时敏感的肺表面活性剂模拟脂质囊泡将通过气溶胶给药为提高紫杉醇的治疗效果提供协同优势。纳米囊泡显示出颗粒的单峰粒径分布（100-150nm）和紫杉醇的高包封效率（82%）。在存在分泌型磷脂酶 A2（secretory phospholipase A2）酶的情况下，在约 42°C 观察到紫杉醇的触发释放，并且在同时使用两种触发剂的情况下观察到最大释放。由于这些纳米囊泡旨在用于治疗肺癌的气溶胶给药，因此对它们进行了工程设计，以具有高表面活性和气道通畅性，以模拟肺表面活性剂的功能。在雾化时，双撞击器的下撞击室中纳米囊泡的高沉积表明它们能够到达肺部的终末区域。纳米囊泡显示出由 A549 细胞促进和 ATP 依赖性的主动摄取。当同时使用两种触发剂时，纳米囊泡的细胞毒性潜力显著增加，IC50 为 49.3nM。总的来说，这些研究表明，多触发响应性脂质纳米囊泡包载紫杉醇具有治疗潜力和优势，优于市售的紫杉醇制剂 Taxol，并表明了在治疗肺癌和肺转移中气溶胶给药的可行性。
