University of Graz, Institute of Pharmaceutical Sciences, Department of Pharmaceutical Technology and Biopharmacy, NAWI Graz, Universitätsplatz 1, 8010 Graz, Austria.
Graz University of Technology, Institute of Inorganic Chemistry, 8010 Graz, Austria.
Eur J Pharm Biopharm. 2019 Jun;139:279-290. doi: 10.1016/j.ejpb.2019.04.009. Epub 2019 Apr 16.
Lyotropic bulk reversed hexagonal and reversed cubic liquid crystalline phases (hexagonal and cubic phases) composed of glycerol monooleate (GM) were used to design the vancomycin hydrochloride's (VHCl) delivery systems aiming to maintain VHCl's therapeutic concentration during 24 h in the eye, locally (as an insert) and/or intravitreally (as a bulk phase injection). Bulk VHCl's hexagonal and cubic phases were successfully prepared by melted homogenization and solvent evaporation method, and then an insert was prepared. The structural characteristics of liquid crystalline phases were studied using cross polarized light microscopy and small angle X-ray scattering technique. The presence of VHCl (1-9.5% w/w VHCl solution) did not exhibit any change in the liquid crystalline phase's structure to another liquid crystalline phase, and showed little effect on the lattice parameter of the existing liquid crystalline phase structure. In order to relate the liquid crystalline phase structure to VHCl's release rate locally into the eye, in-vitro release test of an implant has been done using a simulated tear fluid. VHCl's release in the simulated tear fluid from the cubic phase obeyed Higuchi kinetics, with linear VHCl's release versus the square root of time. The hexagonal phase released VHCl in simulated tear fluid significantly slower than the cubic phase. In order to relate the liquid phase structure to VHCl's diffusion intravitreally, in vitro release test by the Sirius' Subcutaneous Injection Site Simulator (Scissor) has been performed. Comparing the release properties by a Scissor, the VHCl's cubic phase demonstrated slower permeation through extra-cellular matrix than the VHCl solution. To evaluate the efficacy of the system investigated, the release properties of VHCl's cubic phase were compared with literature data indicating that the cubic phase could be a potential matrix system in the delivery of VHCl intravitreally during 24 h after intravitreal injection. The release data in the simulated tear fluid indicated that the cubic phase should be further optimized to achieve a therapeutic VHCl concentration locally in the eye during 24 h.
由甘油单油酸酯（GM）组成的溶致性各向同性反向六方和反向立方液晶相（六方相和立方相）被用于设计盐酸万古霉素（VHCl）的递送系统，旨在在 24 小时内在眼部局部（作为插入物）和/或玻璃体内（作为块状相注射）维持 VHCl 的治疗浓度。通过熔融匀化和溶剂蒸发法成功制备了块状 VHCl 的六方相和立方相，然后制备了插入物。使用偏光显微镜和小角 X 射线散射技术研究了液晶相的结构特征。存在 VHCl（1-9.5％w/w VHCl 溶液）不会使液晶相结构向另一种液晶相发生任何变化，并且对现有液晶相结构的晶格参数几乎没有影响。为了将液晶相结构与局部递送到眼睛中的 VHCl 释放率相关联，已经使用模拟泪液进行了植入物的体外释放试验。立方相中的 VHCl 释放遵循 Higuchi 动力学，VHCl 的释放与时间的平方根呈线性关系。与立方相相比，六方相在模拟泪液中的 VHCl 释放速度明显较慢。为了将液相结构与 VHCl 的玻璃体内扩散相关联，通过 Sirius'皮下注射部位模拟器（剪刀）进行了体外释放试验。通过剪刀比较释放性能，VHCl 的立方相表现出比 VHCl 溶液更慢的通过细胞外基质的渗透。为了评估所研究系统的疗效，将 VHCl 的立方相的释放性能与文献数据进行了比较，表明立方相可能是玻璃体内注射后 24 小时内玻璃体内递 VHCl 的潜在基质系统。在模拟泪液中的释放数据表明，立方相需要进一步优化，以在 24 小时内在眼部局部达到治疗性 VHCl 浓度。
