NanoBioCel Group, Laboratory of Pharmaceutics, School of Pharmacy, University of the Basque Country, Vitoria, Spain; Biomedical Research Networking Centre in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Vitoria, Spain.
Hospital Universitario de Álava (HUA) Txagorritxu, Vitoria 01009, Spain.
J Control Release. 2014 Jul 10;185:51-61. doi: 10.1016/j.jconrel.2014.04.032. Epub 2014 Apr 29.
Lipid nanoparticles are currently receiving increasing interest because they permit the topical administration of proteins, such as recombinant human epidermal growth factor (rhEGF), in a sustained and effective manner. Because chronic wounds have become a major healthcare burden, the topical administration of rhEGF-loaded lipid nanoparticles, namely solid lipid nanoparticles (SLN) and nanostructured lipid carries (NLC), appears to be an interesting and suitable strategy for the treatment of chronic wounds. Both rhEGF-loaded lipid nanoparticles were prepared through the emulsification-ultrasonication method; however, the NLC-rhEGF preparation did not require the use of any organic solvents. The characterisation of the nanoparticles (NP) revealed that the encapsulation efficiency (EE) of NLC-rhEGF was significantly greater than obtained with SLN-rhEGF. The in vitro experiments demonstrated that gamma sterilisation is a suitable process for the final sterilisation because no loss in activity was observed after the sterilisation process. In addition, the proliferation assays revealed that the bioactivity of the nanoformulations was even higher than that of free rhEGF. Finally, the effectiveness of the rhEGF-loaded lipid nanoparticles was assayed in a full-thickness wound model in db/db mice. The data demonstrated that four topical administrations of SLN-rhEGF and NLC-rhEGF significantly improved healing in terms of wound closure, restoration of the inflammatory process, and re-epithelisation grade. In addition, the data did not reveal any differences in the in vivo effectiveness between the different rhEGF-loaded lipid nanoparticles. Overall, these findings demonstrate the promising potential of rhEGF-loaded lipid nanoparticles, particularly NLC-rhEGF, for the promotion of faster and more effective healing and suggest their future application for the treatment of chronic wounds.
脂质纳米粒目前受到越来越多的关注，因为它们可以以持续有效的方式将蛋白质（如重组人表皮生长因子[rheGF]）经皮给药。由于慢性创面已成为主要的医疗保健负担，因此负载 rheGF 的脂质纳米粒（即固体脂质纳米粒[SLN]和纳米结构脂质载体[NLC]）的局部给药似乎是治疗慢性创面的一种有趣且合适的策略。两种负载 rheGF 的脂质纳米粒均通过乳化-超声法制备；然而，NLC-rheGF 制剂无需使用任何有机溶剂。纳米粒（NP）的特性表明，NLC-rheGF 的包封效率（EE）明显大于 SLN-rheGF。体外实验表明，γ 射线灭菌是一种合适的最终灭菌工艺，因为灭菌后未观察到活性丧失。此外，增殖实验表明，纳米制剂的生物活性甚至高于游离 rheGF。最后，在 db/db 小鼠的全层创面模型中检测了负载 rheGF 的脂质纳米粒的疗效。数据表明，SLN-rheGF 和 NLC-rheGF 的四次局部给药显著改善了创面闭合、炎症过程恢复和再上皮化程度，从而提高了愈合效果。此外，数据并未显示不同负载 rheGF 的脂质纳米粒在体内疗效方面存在差异。总之，这些发现表明负载 rheGF 的脂质纳米粒具有很大的应用潜力，特别是 NLC-rheGF，可促进更快、更有效的愈合，并提示其未来在慢性创面治疗中的应用。
