摘要
递送核酸到靶向细胞的安全性和有效性限制了基因治疗的成功率,聚(d,l-丙交酯-共-乙交酯)(PLGA)纳米颗粒(NP)能够有效的递送药物和基因。与其他制剂相比,该制剂的优点在于能够改善溶解性、稳定性、控制包被剂的降解和释放。对于PLGA作为基因载体的应用,还存在许多挑战。PLGA纳米颗粒能够保护包封的DNA免受体内讲解但是DNA的释放比较慢并且负电荷对DNA的掺入和传送会产生阻碍。同时,在制备过程中暴露在高剪切应力和有机溶剂中的DNA会导致失活。此外,PLGA NPs能够用不同的制剂来减少细胞毒性来加强递送效率并靶向特异性组织或细胞。本文综述了制备PLGA NPs的不同方法以及近期用于基因治疗的PLGA颗粒的修饰的策略。
关键词: 聚乳酸-羟基乙酸共聚物、基因递送、包封、修饰、纳米颗粒
Current Medicinal Chemistry
Title:Current Strategies in the Modification of PLGA-based Gene Delivery System
Volume: 24 Issue: 7
关键词: 聚乳酸-羟基乙酸共聚物、基因递送、包封、修饰、纳米颗粒
摘要: Successful gene therapy has been limited by safe and efficient delivery of nucleic acid to the target cells. Poly (d,l-lactide-co-glycolide) (PLGA) nanoparticles (NPs) are able to deliver drugs and genes efficiently. This formulation has several advantages in comparison with other formulations including improvement in solubility, stability, controlling of degradation and release of the entrapped agents. For application of PLGA as a gene carrier, there exist many challenges. PLGA NPs could protect the encapsulated DNA from in vivo degradation but the DNA release is slow and the negative charge acts as a barrier to DNA incorporation and delivery. Also, during the preparation process, DNA could be exposed to high shear stress and organic solvents which could result in its inactivation. Moreover, PLGA NPs could be modified with different agents to reduce cytotoxicity, to enhance delivery efficiency and to target specific tissues/cells. This review summarizes different methods used for the preparation of PLGA NPs as gene carriers and recent strategies for the modification of PLGA particles applied in gene therapy.
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Current Strategies in the Modification of PLGA-based Gene Delivery System, Current Medicinal Chemistry 2017; 24 (7) . https://dx.doi.org/10.2174/0929867324666161205130416
DOI https://dx.doi.org/10.2174/0929867324666161205130416 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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