White Joanna M, Calabrese Michelle A
University of Minnesota, 421 Washington Ave SE, Minneapolis, 55455, MN, USA.
Colloids Surf A Physicochem Eng Asp. 2022 Apr 5;638. doi: 10.1016/j.colsurfa.2021.128246. Epub 2022 Jan 10.
Poloxamer 407 (P407) is widely used for targeted drug-delivery because it exhibits thermoresponsive gelation behavior near body temperature, stemming from a disorder-to-order transition. Hydrophobic small molecules can be encapsulated within P407; however, these additives often negatively impact the rheological properties and lower the gelation temperatures of the hydrogels, limiting their clinical utility. Here we investigate the impact of adding two BAB reverse poloxamers (RPs), 25R4 and 31R1, on the thermal transitions, rheological properties, and assembled structures of P407 both with and without incorporated small molecules. By employing a combination of differential scanning calorimetry (DSC), rheology, and small-angle x-ray scattering (SAXS), we determine distinct mechanisms for RP incorporation. While 25R4 addition promotes inter-micelle bridge formation, the highly hydrophobic 31R1 co-micellizes with P407. Small molecule addition lowers thermal transition temperatures and increases the micelle size, while RP addition mitigates the decreases in modulus traditionally associated with small molecule incorporation. This fundamental understanding yields new strategies for tuning the mechanical and structural properties of the hydrogels, enabling design of drug-loaded formulations with ideal thermal transitions for a range of clinical applications.
泊洛沙姆407（P407）因其在体温附近表现出热响应凝胶化行为（源于无序到有序的转变）而被广泛用于靶向给药。疏水性小分子可以被包裹在P407中；然而，这些添加剂常常会对流变学性质产生负面影响，并降低水凝胶的凝胶化温度，限制了它们的临床应用。在此，我们研究了添加两种BAB型反向泊洛沙姆（RPs），即25R4和31R1，对含有和不含有小分子的P407的热转变、流变学性质及组装结构的影响。通过结合使用差示扫描量热法（DSC）、流变学和小角X射线散射（SAXS），我们确定了RPs掺入的不同机制。添加25R4会促进胶束间桥的形成，而高度疏水的31R1则与P407共胶束化。添加小分子会降低热转变温度并增加胶束尺寸，而添加RPs则减轻了传统上与小分子掺入相关的模量降低。这种基本认识为调节水凝胶的机械和结构性质提供了新策略，从而能够设计出具有理想热转变的载药制剂，用于一系列临床应用。
