Momekova Denitsa, Rangelov Stanislav, Lambov Nikolay
Department of Pharmaceutical Technology and Biopharmaceutics, Faculty of Pharmacy, Medical University-Sofia, Sofia, Bulgaria.
Methods Mol Biol. 2010;605:527-44. doi: 10.1007/978-1-60327-360-2_35.
A major limiting factor for the wide application of pH-sensitive liposomes is their recognition and sequestration by the phagocytes of the reticulo-endothelial system, which conditions a very short circulation half-life. Typically prolonged circulation of liposomes is achieved by grafting their membranes with pegylated phospholipids (PEG-lipids), which have been shown, however, to deteriorate membrane integrity on one hand and to hamper the pH-responsiveness on the other. Hence, the need for novel alternative surface modifying agents to ensure effective half-life prolongation of pH-sensitive liposomes is a subject of intensive research. A series of copolymers having short blocks of lipid-mimetic units has been shown to sterically stabilize conventional liposomes based on different phospholipids. This has prompted us to broaden their utilization to pH-sensitive liposomes, too. The present contribution gives thorough account on the chemical synthesis of these copolymers their incorporation in DOPE:CHEMs pH-sensitive liposomes and detailed explanation on the battery of techniques for the biopharmaceutical characterization of the prepared formulations in terms of pH-responsiveness, cellular internalization, in vivo pharmacokinetics and biodistribution.
pH敏感脂质体广泛应用的一个主要限制因素是它们会被网状内皮系统的吞噬细胞识别并清除，这导致其循环半衰期非常短。通常，通过用聚乙二醇化磷脂（PEG-脂质）嫁接脂质体膜来实现脂质体的循环时间延长，然而，这一方面会破坏膜的完整性，另一方面会妨碍pH响应性。因此，需要新型替代表面改性剂以确保pH敏感脂质体的有效半衰期延长，这是一个深入研究的课题。已证明一系列具有短脂质模拟单元嵌段的共聚物能基于不同磷脂对传统脂质体进行空间稳定化。这促使我们将其应用范围扩大到pH敏感脂质体。本文全面介绍了这些共聚物的化学合成、它们在DOPE:CHEMs pH敏感脂质体中的掺入情况，并详细解释了用于对所制备制剂进行生物药学表征的一系列技术，包括pH响应性、细胞内化、体内药代动力学和生物分布。
