Rational design of block copolymer micelles to control burst drug release at a nanoscale dimension
Rational design of block copolymer micelles to control burst drug release at a nanoscale dimension
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DOI：
10.1016/j.actbio.2015.06.017
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发表时间：
2015-09-15
影响因子：
9.7
通讯作者：
Lavasanifar, Afsaneh
中科院分区：
文献类型：
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作者：
Abyaneh, Hoda Soleymani;Vakili, Mohammad Reza;Lavasanifar, Afsaneh
为了解决聚合物胶束药物突然释放的问题，我们设计了三层ABC胶束，由甲氧基聚环氧乙烷（PEO）作为壳层（A块）；不同立体化学的聚乳酸（PLA）作为外核（B块），聚（α-苄基羧酸酯-ε-己内酯）（PBCL）或聚（ε-己内酯）（PCL）作为内核（C块）。胶束用于封装模型疏水性药物尼莫地平。然后与二嵌段共聚物胶束相比，评估 PLA（B 嵌段）的掺入和立体化学对 ABC 三嵌段共聚物胶束中半结晶外核形成、胶束稳定性、药物负载和释放的影响。由于尼莫地平和 PLA 之间的高 Flory Huggins 相互作用参数 (chi = 1.35)，PLA 外核预计将充当屏障，降低药物从胶束载体中扩散出来的速率。在 ABC 嵌段共聚物胶束中引入 PEA 外核减少了尼莫地平从聚合物胶束中的突然释放，而不损害其高包封效率。在具有立体规整 PEA 嵌段的 ABC 聚合物胶束中；未形成半结晶 PEA 外核，这与 PEO-PLA 二嵌段共聚物胶束相反。因此，PEA 立体化学对 ABC 聚合物胶束中的药物释放没有显着影响。与二嵌段共聚物相反，在由含有 ABC 三嵌段共聚物的 PDLA 和 PLLA 50:50 混合物组成的混合胶束中没有观察到立体络合的迹象。结果表明，正确设计的 ABC 三嵌段共聚物胶束能够作为纳米级尺寸的药物溶解和储库释放的储库。意义说明聚合物胶束是广泛用于药物递送的核-壳纳米结构。它们的疏水性核心可容纳水溶性较差的药物，而其亲水性外壳使整个结构具有水溶性。使用聚合物胶束的一个常见问题是掺入的药物从这些载体中泄漏。在这里，我们证明了正确设计的三层（ABC）嵌段共聚物胶束，其内核具有药物相容性嵌段，外核具有药物不相容性嵌段，可用于降低药物释放的初始快速速率，同时提供封装在内核中的大量药物。此外，内核化学结构的变化可用于改变这些系统的稳定性。 (C) 2015 Acta Materialia Inc. 由 Elsevier Ltd 出版。保留所有权利。
To circumvent the problem of burst drug release from polymeric micelles, we designed three layered ABC micelles consisting of methoxy poly(ethylene oxide) (PEO) as the shell layer (A block); poly(lactic acid) (PLA) of different stereo-chemistries as the outer core (B block) and poly(alpha-benzylcarboxylate-epsilon-caprolac tone) (PBCL) or poly(epsilon-caprolactone) (PCL) as the inner core (C block). The micelles were used to encapsulate a model hydrophobic drug, nimodipine. The effect of PLA (B block) incorporation and stereochemistry on the formation of semi crystalline outer cores in ABC triblock copolymer micelles, micelle stability, drug loading and release was then assessed in comparison to diblock copolymer micelles. The PLA outer core was expected to act as a barrier lowering the rate of drug diffusion out of the micellar carrier owing to a high Flory Huggins interaction parameter between nimodipine and PLA (chi = 1.35). Introduction of PEA outer cores in ABC block copolymer micelles reduced the burst release of nimodipine from polymeric micelles without jeopardizing its high encapsulation efficiency. In ABC polymeric micelles with stereo-regular PEA blocks; semi-crystalline outer PEA cores were not formed, which was in contrast to PEO-PLA diblock copolymer micelles. Accordingly, PEA stereo-chemistry had no significant effect on drug release in ABC polymeric micelles. In contrast to diblock copolymers, no sign of stereo-complexation in mixed micelles composed of a 50:50 mixture of PDLA and PLLA containing ABC triblock copolymers was observed. The results showed the capability of properly designed ABC triblock copolymer micelles as reservoirs for drug solubilization and depot release at nanoscale dimensions.Statement of SignificancePolymeric micelles are core-shell nanostructures that are widely used for drug delivery. Their hydrophobic core accommodates poor water soluble drugs and their hydrophilic shell allows the whole structure to be water soluble. A common problem with the use of polymeric micelles is leakage of the incorporated drug from these carriers. Here we have shown that a properly designed three layered (ABC) block copolymer micelle with drug compatible blocks at the inner core and drug incompatible blocks at the outer core can be used to reduce the initial fast rate of drug release while providing high amount of drug encapsulated in the core. Moreover, changes in the chemical structure of the inner core may be used to modify the stability of these systems. (C) 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.