Institute for Experimental Molecular Imaging, RWTH Aachen University Hospital, 52074 Aachen, Germany.
DWI - Leibniz Institute for Interactive Materials, 52074 Aachen, Germany.
Mol Pharm. 2022 Sep 5;19(9):3256-3266. doi: 10.1021/acs.molpharmaceut.2c00416. Epub 2022 Jul 29.
Gas-filled microbubbles (MB) are routinely used in the clinic as ultrasound contrast agents. MB are also increasingly explored as drug delivery vehicles based on their ultrasound stimuli-responsiveness and well-established shell functionalization routes. Broadening the range of MB properties can enhance their performance in both imaging and drug delivery applications. This can be promoted by systematically varying the reagents used in the synthesis of MB, which in the case of polymeric MB include surfactants. We therefore set out to study the effect of key surfactant characteristics, such as the chemical structure, molecular weight, and hydrophilic-lipophilic balance on the formation of poly(butyl cyanoacrylate) (PBCA) MB, as well as on their properties, including shell thickness, drug loading capacity, ultrasound contrast, and acoustic stability. Two different surfactant families (, Triton X and Tween) were employed, which show opposite molecular weight hydrophilic-lipophilic balance trends. For both surfactant types, we found that the shell thickness of PBCA MB increased with higher-molecular-weight surfactants and that the resulting MB with thicker shells showed higher drug loading capacities and acoustic stability. Furthermore, the higher proportion of smaller polymer chains of the Triton X-based MB (as compared to those of the Tween-based ones) resulted in lower polymer entanglement, improving drug loading capacity and ultrasound contrast response. These findings open up new avenues to fine-tune the shell properties of polymer-based MB for enhanced ultrasound imaging and drug delivery applications.
充气体微泡（MB）在临床上通常用作超声造影剂。MB 也越来越多地被探索作为药物输送载体，基于其超声刺激响应性和成熟的壳功能化途径。拓宽 MB 性质的范围可以增强它们在成像和药物输送应用中的性能。这可以通过系统地改变 MB 合成中使用的试剂来促进，在聚合物 MB 的情况下，这些试剂包括表面活性剂。因此，我们着手研究关键表面活性剂特性（如化学结构、分子量和亲水-亲脂平衡）对聚（正丁基氰基丙烯酸酯）（PBCA）MB 的形成以及对其性质（包括壳厚度、载药能力、超声对比和声学稳定性）的影响。使用了两种不同的表面活性剂家族（Triton X 和 Tween），它们显示出相反的分子量-亲水-亲脂平衡趋势。对于这两种类型的表面活性剂，我们发现 PBCA MB 的壳厚度随高分子量表面活性剂的增加而增加，并且具有较厚壳的所得 MB 显示出更高的载药能力和声学稳定性。此外，基于 Triton X 的 MB 中的较小聚合物链比例较高（与基于 Tween 的 MB 相比）导致较低的聚合物缠结，从而提高了载药能力和超声对比响应。这些发现为精细调整基于聚合物的 MB 的壳性质以增强超声成像和药物输送应用开辟了新途径。
