Abstract：
Investigating the structural integrity of carriers in transit from ocular surface to ocular posterior segment is essential for an efficient topical drug delivery system. In this study, dual-carrier hydroxypropyl-β-cyclodextrin complex@Liposome (HPCD@Lip) nanocomposites were developed for the efficient delivery of dexamethasone. Förster Resonance Energy Transfer with near-infrared I fluorescent dyes and in vivo imaging system were used to investigate the structural integrity of HPCD@Lip nanocomposites after crossing Human conjunctival epithelial cells (HConEpiC) monolayer and in ocular tissues. The structural integrity of inner HPCD complexes was monitored for the first time. The results suggested that 23.1 ± 6.4 % of nanocomposites and 41.2 ± 4.3 % of HPCD complexes could cross HConEpiC monolayer with an intact structure at 1 h. 15.3 ± 8.4 % of intact nanocomposites could reach at least sclera and 22.9 ± 1.2 % of intact HPCD complexes could reach choroid-retina after 60 min in vivo, which showed that the dual-carrier drug delivery system could successfully deliver intact cyclodextrin complexes to ocular posterior segment. In conclusion, in vivo assessment of structural integrity of nanocarriers is greatly significant for guiding the rational design, higher drug delivery efficiency and clinical transformation for topical drug delivery system to the posterior segment of the eye.
摘要：
研究从眼表到眼后段转运的载体的结构完整性对于有效的局部药物递送系统至关重要。在这项研究中,开发了双载体羟丙基-β-环糊精复合物@脂质体（HPCD@Lip）纳米复合材料，用于有效递送地塞米松。使用近红外I荧光染料和体内成像系统进行Förster共振能量转移，以研究穿过人结膜上皮细胞（HConEpiC）单层和眼组织后HPCD@Lip纳米复合材料的结构完整性。首次监测了内部HPCD复合物的结构完整性。结果表明，23.1±6.4％的纳米复合材料和41.2±4.3％的HPCD复合物可以在1h时穿过具有完整结构的HConEpiC单层。在体内60分钟后，完整的纳米复合材料的15.3±8.4％可以达到至少巩膜，完整的HPCD复合物的22.9±1.2％可以达到脉络膜-视网膜。这表明双载体药物递送系统可以成功地将完整的环糊精复合物递送到眼后段。总之,体内评估纳米载体的结构完整性对于指导合理设计非常重要，更高的药物递送效率和临床转化为局部药物递送系统到眼后段。
