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pH-sensitive gel phase liposomes

机译：pH敏感的凝胶相脂质体

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pH-Sensitive liposomes have been proposed for the delivery of membrane impermeable compounds to the cytoplasm following receptor-mediated endocytosis. Unsaturated phsophatidylethanolamine (PE) has been widely employed to confer intrinsic pH-sensitivity to liposomes~1. However, PE-liposomes are generally moderately stable in plasma and destabilization under weakly acidic conditions has been reported only in the case of fluid phase liposomes~1. A novel polymeric-based pH sensitive liposome system in which the polymer triggers the release of liposomal contents at acidic pH was recently described by Meyer et al~2. It was shown that random copolymers of N-isopropylacrylamide (NIPA), methacrylic acid (MAA) and octadecylacrylate (ODA) can destabilize fluid phase liposomes at acidic pH. In this study, the ability of NIPA copolymers to destabilize gel phase liposomes was investigated. The hydrophobic anchor of the copolymer was either randomly grafted or attached to one end of the polymeric chain. The stability in plasma and pharmacokinetics of the polymer-liposomes formulations were also evaluated.
机译：已经提出了pH-敏感的脂质体用于在受体介导的内吞作用后递送膜不可渗透化合物到细胞质中。不饱和膦酸乙醇胺（PE）已广泛用于赋予脂质体的固有pH敏感性〜1。然而，PE-脂质体在血浆中通常在血浆中稳定，并且仅在流体相脂质体〜1的情况下仅报告了弱酸性条件下的稳定化。一种新型基于聚合物的pH敏感脂质体体系，其中聚合物触发了Meyer等，最近描述了酸性pH下脂质体含量的释放。结果表明，N-异丙基丙烯酰胺（NIPA），甲基丙烯酸（MAA）和八烷基丙烯酸酯（ODA）的随机共聚物可以使酸性pH下的流体相脂质体变得稳定。在本研究中，研究了NIPA共聚物以使凝胶相脂质体变得稳定的能力。共聚物的疏水锚定随机接枝或连接到聚合物链的一端。还评价了聚合物 - 脂质体配方的血浆和药代动力学的稳定性。

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