Zelenková Tereza, Fissore Davide, Marchisio Daniele L, Barresi Antonello A
Dipartimento di Scienza Applicata e Tecnologia, Politecnico di Torino, Corso Duca degli Abruzzi 24, Turin, 10129, Italy.
J Pharm Sci. 2014 Jun;103(6):1839-50. doi: 10.1002/jps.23960. Epub 2014 Apr 15.
This work is focused on the control of poly-ε-caprolactone nanoparticle characteristics, notably size and size distribution, in both the production and preservation (by using freeze-drying) stages. Nanoparticles were obtained by employing the solvent displacement method in a confined impinging jets mixer. The effect of several operating conditions, namely, initial polymer concentration and solvent-to-antisolvent flow rate ratio, and the influence of postprocessing conditions, such as final dilution and solvent evaporation, on nanoparticle characteristics was investigated. Further addition of antisolvent (water) after preparation was demonstrated to be effective in obtaining stable nanoparticles, that is, avoiding aggregation that would result in larger particles. On the contrary, solvent (acetone) evaporation was shown to have a small effect on the final nanoparticle characteristics. Eventually, freeze-drying of the solutions containing nanoparticles, after solvent evaporation, was also investigated. To ensure maximum nanoparticles stability, lyoprotectants (e.g., sucrose and mannitol) and steric stabilizers (e.g., Cremophor EL and Poloxamer 388) had to be added to the suspensions. The efficacy of the selected lyoprotectants, in the presence (or absence) of steric stabilizers, and in various concentrations, to avoid particle aggregation during the freeze-drying process was investigated, thus pointing to the optimal formulation.
这项工作聚焦于在聚己内酯纳米颗粒的生产和保存（通过冷冻干燥）阶段对其特性进行控制，尤其是尺寸和尺寸分布。纳米颗粒是通过在受限撞击流混合器中采用溶剂置换法获得的。研究了几种操作条件，即初始聚合物浓度和溶剂与反溶剂的流速比，以及后处理条件（如最终稀释和溶剂蒸发）对纳米颗粒特性的影响。结果表明，制备后进一步添加反溶剂（水）对于获得稳定的纳米颗粒是有效的，即避免会导致颗粒变大的聚集现象。相反，溶剂（丙酮）蒸发对最终纳米颗粒特性的影响较小。最后，还研究了溶剂蒸发后含纳米颗粒溶液的冷冻干燥过程。为确保纳米颗粒的最大稳定性，必须向悬浮液中添加冻干保护剂（如蔗糖和甘露醇）和空间稳定剂（如聚氧乙烯蓖麻油和泊洛沙姆388）。研究了所选冻干保护剂在有（或无）空间稳定剂存在的情况下以及不同浓度下在冷冻干燥过程中避免颗粒聚集的效果，从而确定了最佳配方。
