School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, Dublin 2, Ireland; Université de Lorraine, CITHEFOR, F-54000 Nancy, France.
School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, Dublin 2, Ireland; School of Pharmacy and Medical Sciences, Centre for Pharmaceutical Engineering Science, Faculty of Life Sciences, University of Bradford, Richmond Rd., BD71DP, UK.
Int J Pharm. 2018 Dec 1;552(1-2):27-38. doi: 10.1016/j.ijpharm.2018.09.035. Epub 2018 Sep 17.
This work investigates the impact of nanoparticle (NP) composition and effectiveness of cryo-/lyo-protectants in a freeze drying process, which was employed to convert liquid dispersions of polyelectrolyte complex (PEC) NPs into completely redispersible powders. PEC NPs, with and without peptide, were produced by complex coacervation. The cryo-/lyo-protectants investigated were mannitol, trehalose (TRE) and poly(ethylene glycol) (PEG). The solid state of lyophilised powders was studied by thermal analysis and X-ray diffraction. Cytotoxicity studies were done by MTS assay and flow cytometry. The presence of a cryoprotectant was essential to achieve a successful powder reconstitution. The concentration of TRE was optimised for each type of PEC NPs. Protamine- and hyaluronate-based NPs reconstituted better than chitosan- and chondroitin sulphate-based NPs, respectively. PEG polymers were found to be more effective cryoprotectants than TRE and best results were achieved using co-freeze drying of NPs with TRE and PEG. These ternary NPs/TRE/PEG samples were crystalline, with expected better storage stability. PEG polymers were well tolerated by Caco-2 cells, with the exception of linear PEG 10 kDa. This work shows that, as regards the formulation design and maximising NP loading in the dried product, optimisation of the cryoprotectant type and content is needed as it is highly dependent not only on the type of polyelectrolyte pair in the PEC, but also the polyions ratio.
本研究考察了纳米颗粒（NP）组成和冷冻/干燥保护剂在冷冻干燥过程中的效果，该过程用于将聚电解质复合物（PEC）NP 的液体分散体转化为完全可再分散的粉末。通过复凝聚制备了带和不带肽的 PEC NP。研究的冷冻/干燥保护剂为甘露醇、海藻糖（TRE）和聚乙二醇（PEG）。通过热分析和 X 射线衍射研究了冻干粉末的固体状态。通过 MTS 测定和流式细胞术进行了细胞毒性研究。保护剂的存在对于实现成功的粉末重构至关重要。针对每种类型的 PEC NP 优化了 TRE 的浓度。鱼精蛋白和透明质酸盐基 NP 的重构效果优于壳聚糖和硫酸软骨素基 NP。PEG 聚合物被发现比 TRE 更有效地作为冷冻保护剂，使用 TRE 和 PEG 共冷冻干燥 NPs 可获得最佳结果。这些三元 NPs/TRE/PEG 样品为结晶性，预期具有更好的储存稳定性。除线性 PEG 10 kDa 外，PEG 聚合物均被 Caco-2 细胞良好耐受。本研究表明，就配方设计和最大化干燥产物中 NP 的负载量而言，需要对冷冻保护剂的类型和含量进行优化，因为这不仅高度依赖于 PEC 中聚电解质对的类型，还依赖于聚离子的比例。
