Kari Otto K, Tavakoli Shirin, Parkkila Petteri, Baan Simone, Savolainen Roosa, Ruoslahti Teemu, Johansson Niklas G, Ndika Joseph, Alenius Harri, Viitala Tapani, Urtti Arto, Lajunen Tatu
Drug Research Program, Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, Viikinkaari 5 E, FI-00790 Helsinki, Finland.
Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, P.O. Box 80.082, 3508 TB Utrecht, The Netherlands.
Pharmaceutics. 2020 Aug 12;12(8):763. doi: 10.3390/pharmaceutics12080763.
Light-activated liposomes permit site and time-specific drug delivery to ocular and systemic targets. We combined a light activation technology based on indocyanine green with a hyaluronic acid (HA) coating by synthesizing HA-lipid conjugates. HA is an endogenous vitreal polysaccharide and a potential targeting moiety to cluster of differentiation 44 (CD44)-expressing cells. Light-activated drug release from 100 nm HA-coated liposomes was functional in buffer, plasma, and vitreous samples. The HA-coating improved stability in plasma compared to polyethylene glycol (PEG)-coated liposomes. Liposomal protein coronas on HA- and PEG-coated liposomes after dynamic exposure to undiluted human plasma and porcine vitreous samples were hydrophilic and negatively charged, thicker in plasma (5 nm hard, ~10 nm soft coronas) than in vitreous (2 nm hard, ~3 nm soft coronas) samples. Their compositions were dependent on liposome formulation and surface charge in plasma but not in vitreous samples. Compared to the PEG coating, the HA-coated liposomes bound more proteins in vitreous samples and enriched proteins related to collagen interactions, possibly explaining their slightly reduced vitreal mobility. The properties of the most abundant proteins did not correlate with liposome size or charge, but included proteins with surfactant and immune system functions in plasma and vitreous samples. The HA-coated light-activated liposomes are a functional and promising alternative for intravenous and ocular drug delivery.
光激活脂质体可实现药物向眼部和全身靶点的位点及时间特异性递送。我们通过合成透明质酸（HA）-脂质偶联物，将基于吲哚菁绿的光激活技术与HA包衣相结合。HA是一种内源性玻璃体多糖，也是一种潜在的靶向分化簇44（CD44）表达细胞的靶向部分。100nm HA包衣脂质体的光激活药物释放在缓冲液、血浆和玻璃体样本中均具有功能。与聚乙二醇（PEG）包衣脂质体相比，HA包衣提高了在血浆中的稳定性。在动态暴露于未稀释的人血浆和猪玻璃体样本后，HA包衣和PEG包衣脂质体上的脂质体蛋白冠是亲水性且带负电荷的，在血浆中（5nm硬冠，10nm软冠）比在玻璃体中（2nm硬冠，3nm软冠）更厚。它们的组成取决于脂质体制剂和血浆中的表面电荷，但在玻璃体样本中则不然。与PEG包衣相比，HA包衣脂质体在玻璃体样本中结合了更多蛋白质，并富集了与胶原蛋白相互作用相关的蛋白质，这可能解释了它们在玻璃体中迁移率略有降低的原因。最丰富蛋白质的特性与脂质体大小或电荷无关，但包括血浆和玻璃体样本中具有表面活性剂和免疫系统功能的蛋白质。HA包衣的光激活脂质体是静脉内和眼部药物递送的一种功能性且有前景的替代方案。
