Bin Shen, Zhou Ningfeng, Pan Jie, Pan Fumin, Wu Xiao-Feng, Zhou Zi-Hui
a Department of Spine Surgery , Shanghai East Hospital , Shanghai , China.
b Department of Orthopaedics , Shanghai General Hospital, Shanghai Jiao Tong University, School of Medicine , Shanghai , China.
Drug Dev Ind Pharm. 2017 Jun;43(6):1033-1041. doi: 10.1080/03639045.2017.1291669. Epub 2017 Mar 14.
The objective of this study is to investigate the fate of albumin coupled nanoparticulate system over non-targeted drug carrier in the treatment of hemisectioned spinal cord injury (SCI).
Targeted delivery of methyl prednisolone (MP) and minocycline (MC) portrayed improved therapeutic efficacy as compared with non-targeted nanoparticles (NPS).
Albumin coupled, chitosan stabilized, and cationic NPS (albumin-MP + MC - NPS) of poly-(lactide-co-glycolic acid) were prepared using the emulsion solvent evaporation method. Prepared NPS were characterized for drug entrapment efficiency, particle size, poly-dispersity index (PDI), zeta potential, and morphological characteristics. Their evaluation was done based on the pharmaceutical, toxicological, and pharmacological parameters.
In vitro release of MP + MC from albumin-MP + MC - NPS and MP + MC - NPS was observed to be very controlled for the period of eight days. Cell viability study portrayed non-toxic nature of the developed NPS. Albumin-MP + MC - NPS showed prominent anti-inflammatory potential as compared with non-targeted NPS (MP + MC - NPS) when studied in LPS-induced inflamed astrocytes. Albumin-MP + MC - NPS reduced lesional volume and improved behavioral outcomes significantly in rats with SCI (hemisectioned injury model) when compared with that of MP + MC - NPS.
Albumin-coupled NPS carrier offered an effective method of SCI treatment following safe co-administration of MP and MC. The in vitro and in vivo effectiveness of MP + MC was improved tremendously when compared with the effectiveness showed by MP + MC - NPS. That could be attributed to the site specific, controlled release of MP + MC to the inflammatory site.
本研究的目的是探讨白蛋白偶联纳米颗粒系统与非靶向药物载体相比在治疗半横断脊髓损伤（SCI）中的命运。
与非靶向纳米颗粒（NPS）相比，靶向递送甲基泼尼松龙（MP）和米诺环素（MC）显示出更高的治疗效果。
采用乳液溶剂蒸发法制备白蛋白偶联、壳聚糖稳定的阳离子聚（丙交酯-共-乙交酯）纳米颗粒（白蛋白-MP+MC-NPS）。对制备的纳米颗粒进行药物包封率、粒径、多分散指数（PDI）、zeta电位和形态特征的表征。基于药学、毒理学和药理学参数对其进行评估。
观察到白蛋白-MP+MC-NPS和MP+MC-NPS中MP+MC的体外释放情况在八天内得到很好的控制。细胞活力研究表明所制备的纳米颗粒无毒性。在脂多糖诱导的炎症星形胶质细胞中进行研究时，与非靶向纳米颗粒（MP+MC-NPS）相比，白蛋白-MP+MC-NPS显示出显著的抗炎潜力。与MP+MC-NPS相比，白蛋白-MP+MC-NPS在脊髓损伤（半横断损伤模型）大鼠中显著减少了损伤体积并改善了行为结果。
白蛋白偶联纳米颗粒载体为MP和MC安全联合给药后治疗脊髓损伤提供了一种有效的方法。与MP+MC-NPS相比，MP+MC的体外和体内有效性有了极大提高。这可能归因于MP+MC在炎症部位的位点特异性、控释作用。
