他克莫司载 PEG-胆钙化醇基胶束治疗眼部炎症。
Tacrolimus Loaded PEG-Cholecalciferol Based Micelles for Treatment of Ocular Inflammation.
机构信息
College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, Florida, 32307, USA.
College of Pharmacy and Health Sciences, St. John's University, Queens, New York, 11439, USA.
出版信息
Pharm Res. 2018 Apr 16;35(6):117. doi: 10.1007/s11095-018-2376-7.
PURPOSE
Poor corneal permeability, nasolacrimal drainage and requirement of chronic administration are major drawbacks of existing therapies for ocular inflammation. Hence, we designed topical micelles of PEG conjugated with cholecalciferol (PEGCCF).
METHODS
Integrin targeted tacrolimus loaded PEGCCF micelles (TTM) were prepared by solvent diffusion evaporation method and characterized for particle size, osmolality, encapsulation efficiency and drug loading. Therapeutic potential of TTM was evaluated in benzalkonium chloride induced ocular inflammation model in BALB/c mice. Corneal flourescein staining and histopathological analysis of corneal sections was performed.
RESULTS
TTM had a particle size of 45.3 ± 5.3 nm, encapsulation efficiency (88.7 ± 0.9%w/w) and osmolality of 292-296 mOsmol/Kg. TTM significantly reduced the corneal fluorescence as compared to tacrolimus suspension (TACS). H&E staining showed that TTM could restore corneal epithelial thickness, reduce stromal edema (p < 0.05) and decrease number of inflammatory cells (p < 0.01) compared with TACS. Immunohistochemistry analysis demonstrated lower expression of Ki67 + ve cells (p < 0.05) and IL-6 throughout the cornea against TACS (p < 0.01) and the control (p < 0.001).
CONCLUSIONS
TTM is an innovative delivery system for improving ocular inflammation due to a) integrin targeting b) PEGCCF in the form of carrier and c) anti-inflammatory and synergistic effect (due to Pgp inhibition) with TAC.
目的
目前治疗眼部炎症的方法主要存在角膜通透性差、鼻泪管引流和需要长期给药等缺点。因此，我们设计了聚乙二醇（PEG）偶联胆钙化醇（PEGCCF）的局部胶束。
方法
通过溶剂扩散蒸发法制备整合素靶向他克莫司负载的 PEGCCF 胶束（TTM），并对其粒径、渗透压、包封效率和载药量进行了表征。在 BALB/c 小鼠的苯扎氯铵诱导的眼内炎症模型中评价了 TTM 的治疗潜力。对角膜荧光素染色和角膜切片的组织病理学分析进行了评估。
结果
TTM 的粒径为 45.3±5.3nm，包封效率（88.7±0.9%w/w）和渗透压为 292-296mOsmol/Kg。与他克莫司混悬液（TACS）相比，TTM 显著降低了角膜荧光强度。H&E 染色显示，与 TACS 相比，TTM 可恢复角膜上皮厚度，减轻基质水肿（p<0.05），减少炎症细胞数量（p<0.01）。免疫组织化学分析表明，与 TACS（p<0.01）和对照组（p<0.001）相比，TTM 可降低整个角膜中 Ki67+ve 细胞（p<0.05）和 IL-6 的表达。
结论
TTM 是一种改善眼部炎症的创新给药系统，原因在于：a）整合素靶向，b）PEGCCF 作为载体，c）与 TAC 具有抗炎和协同作用（由于 Pgp 抑制）。
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