Department of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, 69 N. Eagleville Rd, Storrs, Connecticut, 06269, USA.
Department of Chemistry, University of Connecticut, Storrs, Connecticut, 06269, USA.
AAPS PharmSciTech. 2021 Mar 5;22(3):90. doi: 10.1208/s12249-021-01964-5.
Contrast-enhanced X-ray computed tomography plays an important role in cancer imaging and disease progression monitoring. Imaging using radiopaque nanoparticle platforms can provide insights on the likelihood of nanoparticle accumulation and can enable image-guided therapies. Perfluorooctyl bromide (PFOB)-loaded nanocapsules designed for this purpose were stabilized using an in-house synthesized PEGylated polycaprolactone-based copolymer (PEG-b-PCL(Ch)) and compared with commercial polycaprolactone employing a Quality-by-Design approach. PFOB is a dense liquid, weakly polarizable, and immiscible in organic and aqueous solvents; thus, carefully designed formulations for optimal colloidal stabilization to overcome settling-associated instability are required. PFOB-loaded nanocapsules exhibited high PFOB loading due to the intrinsic properties of PEG-b-PCL(Ch). Settling and caking are major sources of instability for PFOB formulations. However, the PEG-b-PCL(Ch) copolymer conferred the nanocapsules enough steric impediment and polymer shell elasticity to settle without significant caking, increasing the overall colloidal stability of the formulation. Furthermore, a clear relationship between nanocapsule physical properties and X-ray attenuation was established. Nanocapsules were able to enhance the X-ray contrast in vitro as a function of PFOB loading. This nanocapsule-based platform is promising for future translational studies and image-guided tumor therapy due to its enhanced contrastability and optimal colloidal stability.
对比增强 X 射线计算机断层扫描在癌症成像和疾病进展监测中发挥着重要作用。使用不透射线纳米颗粒平台进行成像可以提供纳米颗粒积累的可能性的见解，并能够实现图像引导治疗。为此目的设计的负载全氟辛基溴（PFOB）的纳米胶囊使用内部合成的聚乙二醇化聚己内酯基共聚物（PEG-b-PCL（Ch））进行稳定，并与商业聚己内酯采用质量源于设计方法进行比较。PFOB 是一种致密液体，极化率弱，与有机溶剂和水不相溶；因此，需要精心设计的配方以实现最佳胶体稳定化，以克服与沉降相关的不稳定性。由于 PEG-b-PCL（Ch）的固有性质，负载 PFOB 的纳米胶囊表现出高的 PFOB 负载。沉降和结块是 PFOB 制剂不稳定性的主要来源。然而，PEG-b-PCL（Ch）共聚物赋予纳米胶囊足够的空间位阻和聚合物壳弹性，以避免明显的结块，从而提高制剂的整体胶体稳定性。此外，还建立了纳米胶囊物理性质与 X 射线衰减之间的明确关系。纳米胶囊能够作为 PFOB 负载的函数在体外增强 X 射线对比度。由于其增强的对比率和最佳的胶体稳定性，这种基于纳米胶囊的平台有望用于未来的转化研究和图像引导的肿瘤治疗。
