基于人工神经网络优化的达托霉素醇质体制备及评价

Preparation and evaluation of daptomycin-loaded ethosome optimized by artificial neural network

目的制备和评价一种新型纳米制剂—达托霉素醇质体,并考察其治疗局部皮肤感染的效果。方法以遗传算法改良的BP神经网络进行最优处方筛选,从粒径、包封率、载药量、稳定性、体外透皮释放率等方面对新剂型进行评价,并检测其体内外的抗菌活性。结果制备的达托霉素醇质体为规则的球形囊泡,平均粒径为(37.89±0.23)nm,多分散系数为0.243±0.019,药物包封率和载药量分别达到94.09%±4.86%和4.40%±0.27%。体外透皮实验表明醇质体能迅速的渗透进入皮肤,其12h透皮释放率达到82.14%。此外,在体内外环境下,达托霉素醇质体对金葡菌有强效杀灭能力,并且能够穿透金葡菌生物被膜杀灭细菌。结论成功制备出粒径小、包封率高、稳定性好、透皮释放量大、抑菌效果优良的达托霉素醇质体。

Objective To prepare and evaluate a novel nanoformulation, daptomycin ethostreatment of skin infections. Methods The back propagation neural networks optimized by genetic algorithm （BPNN-GA） was used to solve multi-objective optimization of DAP-ETs. The particle size, entrapment capacity, drug-loading rate, stability and cumulative release rate in vitro were evaluated as the assessment index. Moreover, the antibacterial and anti- biofilms effect of omes （DAP-ETs）, for checking the potential in topical DAP-ETs were measured both in vitro and in vivo. Results The obtained formulation showed spherical, regular vesicles with range of （37.89±0.23）nm and a narrow size distribution （polydispersity index 0.243±0.019）. The drug entrapment efficiency and drug-loading rate were 94.09%~4.86% and 4.40%4-0.27% respectively. In vitro skin permeation experiments revealed that DAP-ETs can efficiently permeate and distribute into skins with a percentage of drug permeation content at 82.14% within 12 hours. Furthermore, DAP-ETs exerted powerful effects against Staphylococcus aureus （S. aureus） and formed biofilms both in vitro and in vivo. Conclusion The obtained ethosomes had small size, great entrapment efficiency, good stability and a high level of release rate, which indicate that this novel nanoformulation may have potential in clinical therapies as an alternative delivery approach to the current intravenous administration of daptomycin.