Department of Pharmaceutical Sciences and Center for Drug Delivery and Nanomedicine, College of Pharmacy, University of Nebraska Medical Center, 985830 Nebraska Medical Center , Omaha, NE , USA and.
J Drug Target. 2013 Dec;21(10):981-93. doi: 10.3109/1061186X.2013.831421. Epub 2013 Sep 2.
Polymer nanogels have gained considerable attention as a potential platform for drug delivery applications. Here we describe the design and synthesis of novel polypeptide-based nanogels with hydrophobic moieties in the cross-linked ionic cores. Diblock copolymer, poly(ethylene glycol)-b-poly(L-glutamic acid), hydrophobically modified with L-phenylalanine methyl ester moieties was used for controlled template synthesis of nanogels with small size (ca. 70 nm in diameter) and narrow particle size distribution. Steady-state and time-resolved fluorescence studies using coumarin C153 indicated the existence of hydrophobic domains in the ionic cores of the nanogels. Stable doxorubicin-loaded nanogels were prepared at high drug capacity (30 w/w%). We show that nanogels are enzymatically-degradable leading to accelerated drug release under simulated lysosomal acidic pH. Furthermore, we demonstrate that the nanogel-based formulation of doxorubicin is well tolerated and exhibit an improved antitumor activity compared to a free doxorubicin in an ovarian tumor xenograft mouse model. Our results signify the point to a potential of these biodegradable nanogels as attractive carriers for delivery of chemotherapeutics.
聚合物纳米凝胶作为药物传递应用的潜在平台已经引起了相当大的关注。在这里，我们描述了具有交联离子核中疏水性部分的新型基于多肽的纳米凝胶的设计和合成。用 L-苯丙氨酸甲酯部分疏水改性的两亲性嵌段共聚物聚（乙二醇）-b-聚（L-谷氨酸）用于纳米凝胶的可控模板合成，其粒径小（约 70nm）且粒径分布窄。使用香豆素 C153 的稳态和时间分辨荧光研究表明纳米凝胶的离子核中存在疏水性结构域。在高药物载量（30w/w%）下制备了稳定的阿霉素负载纳米凝胶。我们表明纳米凝胶可酶降解，在模拟溶酶体酸性 pH 下加速药物释放。此外，我们证明与游离阿霉素相比，基于纳米凝胶的阿霉素制剂在卵巢肿瘤异种移植小鼠模型中具有更好的耐受性和抗肿瘤活性。我们的研究结果表明，这些可生物降解的纳米凝胶作为化疗药物传递的有吸引力的载体具有潜力。
