Orthogonal Self-Assembly of Amphiphilic Peptide Hydrogels and Liposomes Results in Composite Materials with Tunable Release Profiles.
Orthogonal Self-Assembly of Amphiphilic Peptide Hydrogels and Liposomes Results in Composite Materials with Tunable Release Profiles.
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DOI：
10.1021/acs.biomac.3c00664
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发表时间：
2023-09
影响因子：
6.2
通讯作者：
J. W. Swain;Claire Y Yang;J. Hartgerink
中科院分区：
文献类型：
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作者：
J. W. Swain;Claire Y Yang;J. Hartgerink
与游离药物相比，自组装纳米材料可提供更高程度的时空控制，因此成为药物输送的有前途的候选材料。然而，突释、靶向不充分以及药物与纳米材料不相容等挑战仍有改进的空间。正交自组装系统的组合可以产生更有用的材料来改善这些弱点。在这项工作中，我们研究了封装脂质体的纳米纤维多域肽（MDP）水凝胶的正交自组装系统。制备带正电和带负电的 MDP，并与带正电、带负电或两性离子脂质体混合，形成总共六种复合材料。我们证明，尽管两个系统都是两亲性的，但它们能够混合同时保留其独立特性。我们表明，改变脂质体或 MDP 的电荷不会阻碍任一系统的自组装或显着影响其流变特性。在所有六种情况下，封装在脂质体-MDP 复合材料中的小分子导致释放速度比单独的 MDP 水凝胶慢。然而，在一种情况下，带正电荷的 MDP 使带负电荷的脂质体不稳定，并导致独特的释放曲线。最后，我们发现 MDP 水凝胶在 24 小时内显着减少了化疗药物阿霉素从其脂质体制剂 Doxil 中的释放。这项工作展示了两亲性正交自组装系统的化学相容性及其药物输送能力的范围。
Self-assembled nanomaterials are promising candidates for drug delivery by providing a higher degree of spatiotemporal control compared to free drugs. However, challenges such as burst release, inadequate targeting, and drug-nanomaterial incompatibility leave room for improvement. The combination of orthogonal self-assembling systems can result in more useful materials that improve upon these weaknesses. In this work, we investigate an orthogonal self-assembling system of nanofibrous MultiDomain Peptide (MDP) hydrogels encapsulating liposomes. Both positively charged and negatively charged MDPs were prepared and mixed with positively charged, negatively charged, or zwitterionic liposomes for a total of six composites. We demonstrate that, despite both systems being amphiphilic, they are able to mix while retaining their independent identities. We show that changing the charge of either liposomes or MDPs does not hinder the self-assembly of either system or significantly affect their rheological properties. In all six cases, small molecules encapsulated in liposome-MDP composites resulted in slower release than was possible in MDP hydrogels alone. However, in one case, positively charged MDPs destabilized negatively charged liposomes and resulted in a unique release profile. Finally, we show that MDP hydrogels substantially decrease the release of chemotherapeutic doxorubicin from its liposomal formulation, Doxil, for 24 h. This work demonstrates the chemical compatibility of amphiphilic, orthogonally self-assembled systems and the range of their drug-delivering capabilities.