Le Huu Van, Dulong Virginie, Picton Luc, Le Cerf Didier
Sciences & Technic Faculty, Univ Rouen Normandie, INSA Rouen Normandie, CNRS, PBS UMR 6270, 76000 Rouen, France.
Pharmaceutics. 2023 Mar 13;15(3):929. doi: 10.3390/pharmaceutics15030929.
The lyophilization of nanogels is practical not only for their long-term conservation but also for adjusting their concentration and dispersant type during reconstitution for different applications. However, lyophilization strategies must be adapted to each kind of nanoformulation in order to minimize aggregation after reconstitution. In this work, the effects of formulation aspects (i.e., charge ratio, polymer concentration, thermoresponsive grafts, polycation type, cryoprotectant type, and concentration) on particle integrity after lyophilization and reconstitution for different types of polyelectrolyte complex nanogels (PEC-NGs) from hyaluronic acid (HA) were investigated. The main objective was to find the best approach for freeze-drying thermoresponsive PEC-NGs from Jeffamine-M-2005-functionalized HA, which has recently been developed as a potential platform for drug delivery. It was found that freeze-drying PEC-NG suspensions prepared at a relatively low polymer concentration of 0.2 g.L with 0.2% (m/v) trehalose as a cryoprotectant allow the homogeneous redispersion of PEC-NGs when concentrated at 1 g.L upon reconstitution in PBS without important aggregation (i.e., average particle size remaining under 350 nm), which could be applied to concentrate curcumin (CUR)-loaded PEC-NGs for optimizing CUR content. The thermoresponsive release of CUR from such concentrated PEC-NGs was also reverified, which showed a minor effect of freeze-drying on the drug release profile.
纳米凝胶的冻干不仅对其长期保存很实用，而且在为不同应用进行复溶时，对于调整其浓度和分散剂类型也很实用。然而，冻干策略必须适用于每种纳米制剂，以尽量减少复溶后的聚集。在这项工作中，研究了配方因素（即电荷比、聚合物浓度、热响应性接枝物、聚阳离子类型、冷冻保护剂类型和浓度）对不同类型的透明质酸（HA）聚电解质复合纳米凝胶（PEC-NGs）冻干和复溶后颗粒完整性的影响。主要目标是找到冻干来自Jeffamine-M-2005功能化HA的热响应性PEC-NGs的最佳方法，Jeffamine-M-2005功能化HA最近已被开发为一种潜在的药物递送平台。研究发现，以0.2%（m/v）海藻糖作为冷冻保护剂，在相对较低的聚合物浓度0.2 g.L下制备的PEC-NG悬浮液进行冻干，当在PBS中复溶并浓缩至1 g.L时，PEC-NGs能够均匀再分散，且无明显聚集（即平均粒径保持在350 nm以下），这可用于浓缩负载姜黄素（CUR）的PEC-NGs以优化CUR含量。还再次验证了这种浓缩的PEC-NGs中CUR的热响应释放，结果表明冻干对药物释放曲线影响较小。
