Laboratory for Biomaterials and Drug Delivery, Department of Anesthesiology, Division of Critical Care Medicine, Children's Hospital Boston, Harvard Medical School, Boston, MA, 02115, US.
Department of Pathology, Brigham and Women's Hospital, Boston, MA, 02115, US.
Nat Commun. 2023 Oct 20;14(1):6659. doi: 10.1038/s41467-023-41946-8.
Insufficient drug loading and leakage of payload remain major challenges in designing liposome-based drug delivery systems. These phenomena can limit duration of effect and cause toxicity. Targeting the rate-limiting step in drug release from liposomes, we modify (aromatized) them to have aromatic groups within their lipid bilayers. Aromatized liposomes are designed with synthetic phospholipids with aromatic groups covalently conjugated onto acyl chains. The optimized aromatized liposome increases drug loading and significantly decreases the burst release of a broad range of payloads (small molecules and macromolecules, different degrees of hydrophilicity) and extends their duration of release. Aromatized liposomes encapsulating the anesthetic tetrodotoxin (TTX) achieve markedly prolonged effect and decreased toxicity in an application where liposomes are used clinically: local anesthesia, even though TTX is a hydrophilic small molecule which is typically difficult to encapsulate. Aromatization of lipid bilayers can improve the performance of liposomal drug delivery systems.
脂质体药物递送系统的设计中，药物载量不足和有效载荷泄漏仍然是主要挑战。这些现象会限制作用持续时间并导致毒性。针对脂质体药物释放的限速步骤，我们对其进行修饰（芳构化），使其脂质双层内具有芳基基团。芳构化脂质体是用具有共价连接到酰基链上的芳基基团的合成磷脂设计的。优化后的芳构化脂质体增加了药物载量，并显著降低了广泛有效载荷（小分子和大分子，不同亲水性程度）的爆发释放，并延长了它们的释放时间。包封麻醉剂河豚毒素（TTX）的芳构化脂质体在脂质体临床上应用中实现了显著延长的效果和降低的毒性，尽管 TTX 是一种亲水性小分子，通常难以包封。脂质双层的芳构化可以改善脂质体药物递送系统的性能。
