Section for Pharmaceutics and Social Pharmacy, Department of Pharmacy, University of Oslo, P. O. Box 1068 Blindern, NO-0316, Oslo, Norway.
Section for Pharmaceutics and Social Pharmacy, Department of Pharmacy, University of Oslo, P. O. Box 1068 Blindern, NO-0316, Oslo, Norway; Department of Pharmaceutical and Pharmacological Sciences, University of Padua, Via Marzolo, 5, 35131, Padua, Italy.
Colloids Surf B Biointerfaces. 2020 Nov;195:111250. doi: 10.1016/j.colsurfb.2020.111250. Epub 2020 Jul 8.
The drug solubilization capacity of poloxamers like Pluronic F127 (PF127, poloxamer 407) is dependent on the physical form of the polymer; i.e. the distribution between unimers, aggregates, and micelles. Further, the formation of micelles can alter the stability and pharmacological activity of a drug molecule. It is therefore important to understand how the micellization process is influenced by the addition of excipients and drug molecules. Curcumin is considered a photosensitizer in antimicrobial photodynamic therapy (aPDT). The aPDT effect is optimized at a poloxamer concentration just below the critical micellar concentration (CMC). We aimed to evaluate the effect of curcumin in the presence of 1% ethanol (EtOH) or dimethyl sulfoxide (DMSO) on PF127 micellization. These organic solvents are commonly used in topical preparations as a cosolvent or penetration enhancer (in the case of DMSO). The micellization process was investigated by UV-vis spectroscopy, dynamic light scattering (DLS), and differential scanning calorimetry (DSC). The micellization process of PF127 was slightly influenced by the addition of 1% EtOH or DMSO; however, the presence of 20 μM curcumin enhanced the effect. Micellization was favored in PBS compared to MilliQ water. Structures were formed between PF127 and curcumin at poloxamer concentrations ≥0.3 μM which facilitated solubilization of the photosensitizer. The optimal PF127 concentration required to solubilize 20 μM curcumin but avoid micellization was in the range 0.3 μM-0.04 mM in PBS in the presence of 1 % EtOH or DMSO. A careful consideration of the curcumin, cosolvents, and PF127 concentrations is required to enhance the curcumin solubility and prevent the PF127 micellization.
聚氧丙烯醚如泊洛沙姆 F127（PF127，泊洛沙姆 407）的药物增溶能力取决于聚合物的物理形态；即单体、聚集物和胶束之间的分布。此外，胶束的形成可以改变药物分子的稳定性和药理学活性。因此，了解胶束化过程如何受赋形剂和药物分子的添加影响非常重要。姜黄素被认为是光动力抗菌治疗（aPDT）中的光敏剂。在低于临界胶束浓度（CMC）的聚氧丙烯醚浓度下，aPDT 效果最佳。我们旨在评估 1%乙醇（EtOH）或二甲基亚砜（DMSO）存在下姜黄素对 PF127 胶束化的影响。这些有机溶剂通常作为共溶剂或渗透增强剂（在 DMSO 的情况下）用于局部制剂。通过紫外-可见分光光度法、动态光散射（DLS）和差示扫描量热法（DSC）研究胶束化过程。添加 1% EtOH 或 DMSO 对 PF127 的胶束化过程略有影响；然而，存在 20 μM 姜黄素会增强这种影响。与 MilliQ 水相比，PF127 在 PBS 中更有利于胶束化。在聚氧丙烯醚浓度≥0.3 μM 时，PF127 与姜黄素之间形成了结构，有利于光敏剂的溶解。在 1% EtOH 或 DMSO 存在下，在 PBS 中，为了溶解 20 μM 姜黄素但避免胶束化，所需的最佳 PF127 浓度范围为 0.3 μM-0.04 mM。需要仔细考虑姜黄素、共溶剂和 PF127 的浓度，以提高姜黄素的溶解度并防止 PF127 胶束化。
