核心分支密度对与聚环氧乙烷末端接枝的树胶状聚(γ-苄基 L-谷氨酸)药物释放的影响

Mosa H. Alsehli, Mario Gauthier
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引用次数: 0

摘要

研究人员合成、表征并评估了 G1 代和 G2 代树枝状聚(γ-苄基 L-谷氨酸)(PBG)两亲树枝状共聚物(PBG-eg-PEO),并在其链端接枝了聚(环氧乙烷)(PEO)片段(PBG-eg-PEO),将其作为多柔比星(DOX)的纳米载体。设计的共聚物具有三种不同支化密度的疏水性 PBG 核心,并通过质子核磁共振(1H NMR)光谱、尺寸排阻色谱(SEC)、透射电子显微镜(TEM)和原子力显微镜(AFM)进行了表征。动态光散射(DLS)测量结果表明,这些两亲性分子在磷酸盐缓冲盐水(PBS)等水介质中表现得像单分子胶束,没有明显的聚集现象,直径在 13-29 纳米范围内,具体取决于代数和核心结构。经紫外光谱测定,这些单分子胶束对 DOX 的有效包封能力高达 11.2 wt%,药物负载效率高达 67%,并具有 pH 响应性持续释药功能。研究发现,共聚物的世代数和树枝状 PBG 核心的分支密度会影响胶束的封装和释放特性。鉴于合成两亲树枝状共聚物所用的成分具有可定制的特性、良好的水分散性和生物相容性,这些系统应可用作多种治疗和诊断药物的强效纳米载体。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Influence of the Core Branching Density on Drug Release from Arborescent Poly(γ-benzyl L-glutamate) End-Grafted with Poly(ethylene oxide)
Amphiphilic dendritic copolymers of arborescent poly(γ-benzyl L-glutamate) (PBG) of generations G1 and G2, grafted at their chain ends with poly(ethylene oxide) (PEO) segments (PBG-eg-PEO) were synthesized, characterized, and evaluated as nanocarriers for doxorubicin (DOX). The copolymers were designed with hydrophobic PBG cores having three different branching densities and were characterized by proton nuclear magnetic resonance (1H NMR) spectroscopy, size exclusion chromatography (SEC), transmission electron microscopy (TEM), and atomic force microscopy (AFM). Dynamic light scattering (DLS) measurements revealed that these amphiphilic molecules behaved like unimolecular micelles without significant aggregation in aqueous media such as phosphate-buffered saline (PBS), with diameters in the 13–29 nm range depending on the generation number and the core structure. Efficient encapsulation of DOX by these unimolecular micelles was demonstrated with drug loading capacities of up to 11.2 wt%, drug loading efficiencies of up to 67%, and pH-responsive sustained drug release, as determined by UV spectroscopy. The generation number of the copolymers and the branching density of the dendritic PBG core were found to have influenced the encapsulation and release properties of the micelles. Given the tailorable characteristics, good water dispersibility, and biocompatibility of the components used to synthesize the amphiphilic arborescent copolymers, these systems should be useful as robust nanocarriers for a broad range of therapeutic and diagnostic agents.
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