Pilot-Scale Optimization of the Solvent Exchange Production and Lyophilization Processing of PEG–PLA Block Copolymer-Encapsulated CaWO 4 Radioluminescent Nanoparticles for Theranostic Applications
Pilot-Scale Optimization of the Solvent Exchange Production and Lyophilization Processing of PEG–PLA Block Copolymer-Encapsulated CaWO 4 Radioluminescent Nanoparticles for Theranostic Applications
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用于治疗诊断应用的 PEG-PLA 嵌段共聚物封装的 CaWO 4 放射发光纳米颗粒的溶剂交换生产和冻干工艺的中试规模优化
DOI：
10.1021/acs.iecr.0c05852
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发表时间：
2021
影响因子：
4.2
通讯作者：
Won, You-Yeon
中科院分区：
文献类型：
--
作者：
Patel, Anish P.;Schorr, Christopher R.;Viswanath, Dhushyanth;Sarkar, Kaustabh;Streb, Natalie J.;Pizzuti, Vincenzo J.;Misra, Rahul;Lee, Jaewon;Won, You-Yeon
以往的研究表明，钨酸钙纳米颗粒(NPs)可作为放射增敏/X射线造影剂用于癌症治疗。然而，由于钨酸钙在生理溶液中容易团聚，需要通过溶剂交换过程将这些纳米粒子包裹在聚乙二醇-聚(d，L-乳酸)聚合物胶束中。考察了溶剂类型、聚合物与NP的比例、混合方式、冷冻干燥等工艺参数，优化了包封剂的包装和储存工艺，为以后的规模化生产奠定了基础。在此，我们报告了以前在这一过程中使用的助溶剂(二甲基甲酰胺)可以被毒性较低的助溶剂(丙酮)所取代，聚合物与NP的比例可以从600：1降低到50：1，而不需要增加20%的颗粒尺寸，并且混合方法可以产生更均匀的颗粒分布和更少的多分散。此外，我们的结果表明，与甘露醇相比，蔗糖作为冷冻干燥辅料在冷冻干燥过程中产生的凝块较少。相对分子质量为2 kDa和2 kDa(“2k-2k”)的聚乙二醇聚乳酸在冷冻干燥过程中不易团聚。
Previous studies have shown that calcium tungstate (CaWO4) nanoparticles (NPs) can be used as a radiosensitizing/X-ray contrast agent for cancer treatment. However, due to the propensity of calcium tungstate to agglomerate in physiological solutions, there is a need to encapsulate these NPs within poly(ethylene glycol)-poly(d,l-lactic acid) (PEG–PLA) polymeric micelles through a solvent exchange process. Several parameters including solvent type, polymer to NP ratio, mixing method, and lyophilization were studied to optimize the encapsulation and storage procedures for future scale-up. Herein, we report that the cosolvent that was previously used in this procedure (dimethylformamide) can be replaced with a less toxic cosolvent (acetone), the polymer to NP ratio can be reduced from 600:1 to 50:1 without increasing the particle size by 20%, and mixing methods that create a more uniform flow field produce a more homogenous and less polydisperse particle distribution. In addition, our results indicate that sucrose as a lyophilization excipient produces less agglomeration during freeze-drying compared to mannitol. The smaller molecular weight 2 kDa and 2 kDa (“2 k–2 k”) PEG–PLA was less prone to agglomeration during freeze-drying compared to 5 k–5 k PEG–PLA.