Block copolymer micelles as nanocontainers for controlled release of proteins from biocompatible oil phases.
Block copolymer micelles as nanocontainers for controlled release of proteins from biocompatible oil phases.
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DOI：
10.1021/bm800913r
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发表时间：
2009-04-13
影响因子：
6.2
通讯作者：
Irvine, Darrell J.
中科院分区：
文献类型：
--
作者：
Miller, Andrew C.;Bershteyn, Anna;Tan, Wui Siew;Hammond, Paula T.;Cohen, Robert E.;Irvine, Darrell J.
生物相容性油用于从疫苗佐剂到口服药物递送载体的各种医疗应用中。为了使这种非极性有机相能够作为递送亲水性化合物的储库，我们探索了嵌段共聚物胶束在有机溶剂中螯合蛋白质以在油-水界面上持续释放的能力。研究了嵌段共聚物聚（α-己内酯）-嵌段-聚（2-乙烯基吡啶）（PCL-b-P2 VP）在甲苯和油酸（一种生物相容的天然脂肪酸）中的自组装。胶束在甲苯中的形成，其特征在于通过动态光散射（DLS）和原子力显微镜（AFM）成像的胶束浇铸到硅衬底上。低温透射电子显微镜证实了在油酸的球形形态。均聚物溶解性的研究表明，胶束在油酸中由P2 VP冠和PCL核心，而P2 VP形成的胶束在甲苯中组装的核心。两个模型蛋白质（卵清蛋白（ova）和牛血清白蛋白（BSA））到胶束中的负载被证明与高达7.8%重量的蛋白质每重量的P2 VP在油酸中的负载。在两种溶剂中的嵌段共聚物形态的表征后，蛋白质加载显示球形颗粒具有相似的尺寸分布的组装胶束。将油相与水浴接触后，卵从油酸胶束中的释放持续12 - 30 h。独特的胶束组装在油相中的情况下，数据表明蛋白质被螯合在油酸中的PCL-b-P2 VP胶束的P2 VP冠状块。更常规地，蛋白质负载发生在甲苯中组装的胶束的P2 VP核心中。
Biocompatible oils are used in a variety of medical applications ranging from vaccine adjuvants to vehicles for oral drug delivery. To enable such nonpolar organic phases to serve as reservoirs for delivery of hydrophilic compounds, we explored the ability of block copolymer micelles in organic solvents to sequester proteins for sustained release across an oil−water interface. Self-assembly of the block copolymer, poly(ϵ-caprolactone)-block-poly(2-vinyl pyridine) (PCL-b-P2VP), was investigated in toluene and oleic acid, a biocompatible naturally occurring fatty acid. Micelle formation in toluene was characterized by dynamic light scattering (DLS) and atomic force microscopy (AFM) imaging of micelles cast onto silicon substrates. Cryogenic transmission electron microscopy confirmed a spherical morphology in oleic acid. Studies of homopolymer solubility implied that micelles in oleic acid consist of a P2VP corona and a PCL core, while P2VP formed the core of micelles assembled in toluene. The loading of two model proteins (ovalbumin (ova) and bovine serum albumin (BSA)) into micelles was demonstrated with loadings as high as 7.8% wt of protein per wt of P2VP in oleic acid. Characterization of block copolymer morphology in the two solvents after protein loading revealed spherical particles with similar size distributions to the as-assembled micelles. Release of ova from micelles in oleic acid was sustained for 12−30 h upon placing the oil phase in contact with an aqueous bath. Unique to the situation of micelle assembly in an oily phase, the data suggest protein is sequestered in the P2VP corona block of PCL-b-P2VP micelles in oleic acid. More conventionally, protein loading occurs in the P2VP core of micelles assembled in toluene.
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