Department of Pharmaceutical Sciences, College of Pharmacy, Northeast Ohio Medical University, Rootstown, OH 44272, USA.
Colloids Surf B Biointerfaces. 2012 Jun 1;94:259-65. doi: 10.1016/j.colsurfb.2012.02.005. Epub 2012 Feb 14.
The main objective of the study is to investigate the efficacy of Gelucire 44/14 (gelucire) in facilitating formation of cetyl alcohol (CA)-based nanoparticle (NP) and to assess the effects on key NP properties and functions. NPs from oil-in-water nanoemulsion precursors were prepared using binary mixtures of CA and gelucire (CA/gelucire) containing gelucire at 0, 25, 50 and 75% (w/w). The sizes of gelucire-based NPs (128-183 nm) were five times lower than control NPs (made without gelucire). All the NPs (with or without gelucire component) did not activate macrophages as monitored by reactive oxygen species production. Results from differential scanning calorimetry, FT-IR and multimodal light scattering measurements demonstrated the involvement of gelucire component in achieving homogeneous CA/gelucire particle populations that were stable on storage. The P-glycoprotein (P-gp) function assay in MES-Dx5 cells showed the potential of gelucire-based NPs in inhibiting rhodamine 123 efflux. Similarly, the extent of NP uptake by macrophage (RAW 264.7 cell) was dependent on the amount of gelucire component (inverse relationship; R(2)=0.996). NPs made with CA/gelucire mixture (at 50%, w/w gelucire) were the most effective in blood circulation studies in BALB/c mice. Additional studies with paclitaxel-loaded NPs demonstrated that the retention of gelucire-based NPs in blood circulation was comparable to NPs coated with DSPE-PEG(2000) (p>0.6). The over-all work indicated the potential efficacy of gelucire as a safe and biocompatible excipient that can serve multiple functions in enhancing the performance of lipid-based NP drug delivery systems.
本研究的主要目的是考察 Gelucire 44/14（ Gelucire ）在促进十六醇（CA）为基础的纳米颗粒（NP）形成中的功效，并评估其对关键 NP 性质和功能的影响。通过使用包含 Gelucire 0、25、50 和 75%（w/w）的 CA 和 Gelucire （CA/Gelucire）的油水纳米乳液前体制备 NP。 Gelucire 基 NP（128-183nm）的大小是没有 Gelucire 的对照 NP（没有 Gelucire）的五倍。所有的 NP（具有或不具有 Gelucire 成分）都没有像监测活性氧产生那样激活巨噬细胞。差示扫描量热法、FT-IR 和多模态光散射测量的结果表明， Gelucire 成分的参与有助于实现均匀的 CA/Gelucire 颗粒群，这些颗粒群在储存时是稳定的。在 MES-Dx5 细胞中的 P-糖蛋白（P-gp）功能测定表明， Gelucire 基 NP 具有抑制罗丹明 123 外排的潜力。同样，巨噬细胞（RAW 264.7 细胞）摄取 NP 的程度取决于 Gelucire 成分的量（反比关系；R（2）=0.996）。在 BALB/c 小鼠的血液循环研究中，用 CA/Gelucire 混合物（50%w/w Gelucire）制成的 NP 最为有效。用紫杉醇负载的 NP 进行的进一步研究表明， Gelucire 基 NP 在血液循环中的保留与用 DSPE-PEG（2000）涂覆的 NP 相当（p>0.6）。总的来说，这项工作表明 Gelucire 作为一种安全和生物相容的赋形剂具有潜在的功效，它可以在增强基于脂质的 NP 药物传递系统的性能方面发挥多种功能。
