Department of Chemical and Biomolecular Engineering, The University of Melbourne, Parkville, Victoria 3010, Australia.
Biomaterials. 2011 Sep;32(26):6277-84. doi: 10.1016/j.biomaterials.2011.05.011. Epub 2011 Jun 1.
The design of polymer carriers with tunable degradation and cargo release is fundamental for applications in drug and gene delivery. In this study, we report low-fouling poly(N-vinyl pyrrolidone) (PVPON) capsules assembled via hydrogen bonding and stabilized using covalent cross-linking. We first investigated the effects of pH and ionic strength to optimize the assembly conditions. A model therapeutic cargo (plasmid DNA) was then loaded in the capsules and used for encapsulation and release studies. Two bisazide cross-linkers that contain a disulfide bond, termed PEG₈ (poly(ethylene glycol)) and PEG(16), were employed to stabilize the multilayer films, and used to tune the degradation and cargo release behavior of the capsules in simulated cytoplasmic conditions. The results suggest that PEG₈-stabilized capsules were more efficiently cross-linked, and hence displayed higher plasmid encapsulation. Consequently, the capsules cross-linked with PEG₈ also showed a two-fold reduction in degradation rate. This ability to achieve controlled carrier degradation and cargo release makes these capsules of potential interest for drug and gene delivery.
具有可调降解和货物释放的聚合物载体的设计对于药物和基因递送的应用至关重要。在这项研究中，我们报告了通过氢键组装的低污染聚（N-乙烯基吡咯烷酮）（PVPON）胶囊，并通过共价交联进行稳定。我们首先研究了 pH 值和离子强度对优化组装条件的影响。然后，将模型治疗性货物（质粒 DNA）装载在胶囊中，并用于封装和释放研究。两种含有二硫键的双叠氮交联剂，称为 PEG₈（聚（乙二醇））和 PEG(16)，被用于稳定多层膜，并用于在模拟细胞质条件下调节胶囊的降解和货物释放行为。结果表明，PEG₈稳定的胶囊交联效率更高，因此显示出更高的质粒包封效率。因此，用 PEG₈交联的胶囊的降解速率也降低了两倍。这种实现控制载体降解和货物释放的能力使这些胶囊在药物和基因递送方面具有潜在的应用价值。
