Department of Chemical Engineering and Materials Science, University of Minnesota, Minneapolis, MN 55455, USA.
Department of Mechanical Engineering, University of Minnesota, Minneapolis, MN 55455, USA.
Int J Pharm. 2023 Mar 25;635:122744. doi: 10.1016/j.ijpharm.2023.122744. Epub 2023 Feb 19.
When exposed to an external electric field, lipid bilayer membranes are subject to increased permeability through the generation of pores. Combining this phenomenon, known as electroporation, with liposomal drug delivery offers the added benefit of on-demand release of the liposomal cargo. In previous studies, the maximum percent drug release when exposing liposomes to a pulsed electric field has not surpassed 30%, indicating most of the drug is still retained in the liposomes. Here we showed that by modulating the fluidity of the liposome membrane through appropriate selection of the primary lipid, as well as the addition of other fluidity modulating components such as cholesterol and biotinylated lipid, the electroporation-induced percent release could be increased to over 50%. In addition to improved induced release from liposomes in suspension, biomaterial scaffold-bound liposomes were developed. Electroporation-induced protein release from this solid phase was verified after performing further optimization of the liposome formulation to achieve increased stability at physiological temperatures. Collectively, this work advances the ability to achieve efficient electroporation-induced liposomal drug delivery, which has the potential to be used in concert with other clinical applications of electroporation, such as gene electrotransfer and irreversible electroporation (IRE), in order to synergistically increase treatment efficacy.
当脂质双层膜暴露于外电场时，会通过形成孔而增加通透性。将这种现象（称为电穿孔）与脂质体药物递送结合使用，具有按需释放脂质体货物的额外益处。在以前的研究中，当将脂质体暴露于脉冲电场时，最大药物释放百分比未超过 30%，这表明大部分药物仍保留在脂质体中。在这里，我们通过适当选择主要脂质以及添加其他流动性调节剂成分（如胆固醇和生物素化脂质）来调节脂质体膜的流动性，表明电穿孔诱导的药物释放百分比可增加到 50%以上。除了提高悬浮液中脂质体的诱导释放外，还开发了生物材料支架结合的脂质体。通过进一步优化脂质体配方以实现生理温度下的稳定性来提高，从而验证了这种固态电穿孔诱导的蛋白质释放。总之，这项工作提高了实现高效电穿孔诱导的脂质体药物递送的能力，这有可能与电穿孔的其他临床应用（如基因电转移和不可逆电穿孔（IRE））协同使用，以协同提高治疗效果。
