Acid-cleavable polymeric core-shell particles for delivery of hydrophobic drugs
Acid-cleavable polymeric core-shell particles for delivery of hydrophobic drugs
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DOI：
10.1016/j.jconrel.2006.07.025
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发表时间：
2006-10-10
影响因子：
10.8
通讯作者：
Kavallaris, Maria
中科院分区：
文献类型：
--
作者：
Chan, Yannie;Bulmus, Volga;Kavallaris, Maria
在这里，我们描述了结合使用酸不稳定的微凝胶方法和raft介导的种子分散聚合技术，制备了一个酸可切割的核-壳状聚合物胶体体系，用于在微酸性位点递送疏水药物。采用分散聚合技术，在RAFT试剂的存在下，将新型双丙烯酸酯缩醛交联剂与丙烯酸正丁酯（BA）共聚，得到了粒径在150 ~ 500 nm之间的交联球形颗粒。颗粒以ph依赖的方式裂解，类似于交联剂的酸不稳定水解行为。为了掩盖颗粒的疏水表面，通过颗粒表面的RAFT基团将聚乙二醇丙烯酸酯（PEG-A）接枝到聚（BA）种子颗粒上。采用亲脂性荧光染料作为模型疏水药物，体外评估了聚(BA)-g-聚（PEG-A）颗粒的酸位点选择性递送电位。在pH 5.0和7.4的条件下，在24 h内，载于颗粒中的总染料分别有73%和34%被释放。当核壳颗粒及其裂解副产物浓度达到3mg /ml时，对人神经母细胞瘤细胞的生长无影响。物理化学和功能特征支持了酸可切割聚（BA）核聚（PEG-A）壳颗粒作为在酸性位点递送疏水药物的载体的潜在价值。(c) 2006 Elsevier B.V.版权所有
Here we describe the combined use of acid-labile microgel approach and RAFT-mediated seeded dispersion polymerization technique to prepare an acid-cleavable core-shell like polymeric colloidal system for the delivery of hydrophobic drugs at slightly acidic sites. A new bisacrylate acetal crosslinker was copolymerized with n-butyl acrylate (BA) in the presence of a RAFT agent using a dispersion polymerization technique, which yielded crosslinked spherical particles with the size ranging between 150 and 500 nm. The particles were cleaved in a pH-dependent manner similar to the acid-labile hydrolysis behaviour of the crosslinker. In order to mask the hydrophobic surface of the particles, polyethylene glycol acrylate (PEG-A) was grafted onto poly(BA) seed particles via the RAFT agent groups on the particle surface. The acidic-site selective delivery potential of the poly(BA)-g-poly(PEG-A) particles was assessed in-vitro using a lipophilic fluorescent dye as a model hydrophobic drug. Ca. 73% and 34% of the total dye loaded in the particles was found to be released at pH 5.0 and 7.4 in 24 h, respectively. The growth of human neuroblastoma cells was not affected by the incubation with the core-shell particles and their cleavage by-products up to 3 mg/ml concentration. The physicochemical and the functional features support the potential value of the acid-cleavable poly(BA) core-poly(PEG-A) shell particles as carriers for the delivery of hydrophobic drugs at acidic sites. (c) 2006 Elsevier B.V. All rights reserved.