Ionically Cross-Linked Polymer Networks for the Multiple-Month Release of Small Molecules.
Ionically Cross-Linked Polymer Networks for the Multiple-Month Release of Small Molecules.
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DOI：
10.1021/acsami.5b10070
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发表时间：
2016-02
影响因子：
9.5
通讯作者：
Lapitsky Y
中科院分区：
文献类型：
--
作者：
Lawrence PG;Patil PS;Leipzig ND;Lapitsky Y
从水凝胶中长期（数周或数月）释放水溶性小分子仍然是一项重大的制药挑战，通常要以更复杂的药物载体设计为代价来克服这一挑战。这些方法是有效载荷特异性的，包括药物与基础材料的共价缀合或微米和纳米颗粒的掺入。作为一个更简单的替代方案，在这里，我们报告了一种温和而简单的方法，用于实现从凝胶状聚合物网络中释放小分子的数月。通过聚（烯丙基胺盐酸盐）（PAH）与焦磷酸盐（PPi）或三聚磷酸盐（TPP）的离子凝胶化制备了密集交联的基质，所有这些都是常见的商业分子。这些聚合物网络内的模型小分子（Fast绿色FCF和罗丹明B染料）的负载随着有效载荷/网络结合强度以及封装期间使用的PAH和有效载荷浓度而增加。一旦被加载到PAH/PPi和PAH/TPP离子网络中，只有百分之几的有效载荷在数月内释放。无论有效负载/网络结合强度如何，都实现了这种延长释放，并且可能反映了凝胶样基质内的小流体动力学网格尺寸。此外，PAH/TPP网络与模型细胞（人皮肤成纤维细胞）显示出有前途的体外细胞相容性，尽管PAH/PPi网络表现出轻微的细胞毒性作用。综上所述，上述发现表明PAH/PPi和（特别是）PAH/TPP网络可能是用于药物和其他活性分子（例如，芳香剂或消毒剂）。
Long-term (multiple-week or -month) release of small, water-soluble molecules from hydrogels remains a significant pharmaceutical challenge, which is typically overcome at the expense of more-complicated drug carrier designs. Such approaches are payload-specific and include covalent conjugation of drugs to base materials or incorporation of micro- and nanoparticles. As a simpler alternative, here we report a mild and simple method for achieving multiple-month release of small molecules from gel-like polymer networks. Densely cross-linked matrices were prepared through ionotropic gelation of poly(allylamine hydrochloride) (PAH) with either pyrophosphate (PPi) or tripolyphosphate (TPP), all of which are commonly available commercial molecules. The loading of model small molecules (Fast Green FCF and Rhodamine B dyes) within these polymer networks increases with the payload/network binding strength and with the PAH and payload concentrations used during encapsulation. Once loaded into the PAH/PPi and PAH/TPP ionic networks, only a few percent of the payload is released over multiple months. This extended release is achieved regardless of the payload/network binding strength and likely reflects the small hydrodynamic mesh size within the gel-like matrices. Furthermore, the PAH/TPP networks show promising in vitro cytocompatibility with model cells (human dermal fibroblasts), though slight cytotoxic effects were exhibited by the PAH/PPi networks. Taken together, the above findings suggest that PAH/PPi and (especially) PAH/TPP networks might be attractive materials for the multiple-month delivery of drugs and other active molecules (e.g., fragrances or disinfectants).