Zhang Qianyu, Li Sai, Wu Wen, Xia Xuefeng, Zhang Jinqiang
College of Pharmacy, Chongqing Medical University, Chongqing 400016, China.
School of Pharmaceutical Sciences, Chongqing University, Chongqing 401331, China.
Nanomedicine. 2023 Jan;47:102622. doi: 10.1016/j.nano.2022.102622. Epub 2022 Oct 21.
PASylation, which was recently reported as the conjugation of pharmacologically active compounds with polypeptide sequences mainly made of proline, alanine and serine, has been proposed as an alternative to PEGylation. In this study, we designed PAS-modified liposomes (PASylated liposomes) and studied the effect of the incorporation of PAS-lipid on the stability and pharmacokinetic properties of liposomes, and compared them both in vitro and in vivo to PEGylated liposomes. Results showed that PASylated liposomes modified with single-chained PAS-lipid C-(PA) (SC-PAS-Lip) showed comparable storage and serum stability to PEGylated liposomes (PEG-Lip), and a significantly decreased macrophage uptake compared with unmodified liposomes. SC-PAS-Lip displayed long circulating pharmacokinetic profile which was not impacted by the repeated administration of liposomes, and they were less likely to induce the production of anti-PEG IgM compared with PEGylated liposomes, presenting PASylation as an alternative liposome modification strategy to PEGylation.
PASylation，最近被报道为将药理活性化合物与主要由脯氨酸、丙氨酸和丝氨酸组成的多肽序列进行缀合，已被提议作为聚乙二醇化的替代方法。在本研究中，我们设计了PAS修饰的脂质体（PASylated脂质体），研究了PAS-脂质掺入对脂质体稳定性和药代动力学性质的影响，并在体外和体内将它们与聚乙二醇化脂质体进行比较。结果表明，用单链PAS-脂质C-(PA)（SC-PAS-Lip）修饰的PASylated脂质体与聚乙二醇化脂质体（PEG-Lip）具有相当的储存稳定性和血清稳定性，与未修饰的脂质体相比，巨噬细胞摄取显著降低。SC-PAS-Lip显示出长循环药代动力学特征，不受脂质体重复给药的影响，与聚乙二醇化脂质体相比，它们诱导抗PEG IgM产生的可能性较小，表明PASylation是聚乙二醇化的一种替代脂质体修饰策略。
