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Wormlike Nanovector with Enhanced Drug Loading Using Blends of Biodegradable Block Copolymers.
Biomacromolecules ( IF 6.2 ) Pub Date : 2020-03-25 , DOI: 10.1021/acs.biomac.0c00169
Roxane Ridolfo 1 , Jeanrick J Arends 1 , Jan C M van Hest 1 , David S Williams 2
Affiliation  

The application of nanoparticles comprising amphiphilic block copolymers for the delivery of drugs is a subject of great interest as they hold promise for more effective and selective therapies. In order to achieve this ambition, it is of critical importance to develop our understanding of the self-assembly mechanisms by which block copolymers undergo so that we can control their morphology, tune their ability to be loaded with biofunctional cargoes, and optimize their interactions with target cells. To this end, we have developed a strategy by which blends of (biocompatible) amphiphilic block copolymers generate nonspherical nanovectors, simultaneously enhancing drug loading without the need for subsequent purification owing to the use of the biocompatible direct hydration approach. The principal morphology achieved using this blending strategy are wormlike nanovectors (nanoworms, NWs), with an elongated form known to have a profound effect on flow behavior and interactions with cells. Unloaded nanoworms are not toxic toward human retinal (ARPE-19) cells and can be effectively endocytosed even after varying the surface charge. In terms of drug loading, we demonstrate that uptake of dexamethasone (DEX; a clinically relevant therapeutic agent) in nanoworms (DEX@NWs) can be enhanced using this process, increasing drug content up to 0.5 mg/mL (10 wt % in particles). Furthermore, such nanoworms are stable for at least 5 months and are, therefore, a promising platform for nanomedicine applications.

中文翻译:

使用可生物降解的嵌段共聚物的混合物增强药物负荷的蠕虫状纳米载体。

包含两亲性嵌段共聚物的纳米颗粒在药物递送中的应用引起了广泛的关注,因为它们有望实现更有效和选择性的治疗。为了实现这一雄心壮志,至关重要的是加深我们对嵌段共聚物所经历的自组装机制的了解,以便我们能够控制其形态,调节其装载生物功能货物的能力,并优化它们与以下物质的相互作用:靶细胞。为此,我们已经开发出一种策略,通过该策略,(生物相容性)两亲嵌段共聚物的共混物可生成非球形纳米载体,同时由于使用生物相容性直接水化方法而无需后续纯化即可提高药物载量。使用这种混合策略实现的主要形态是蠕虫状纳米载体(纳米蠕虫,NW),其细长形式已知对流动行为和与细胞的相互作用具有深远的影响。卸载的纳米蠕虫对人视网膜(ARPE-19)细胞无毒,即使在改变表面电荷后也可以被有效地内吞。在药物载量方面,我们证明了使用该方法可以增强纳米蠕虫(DEX @ NWs)中地塞米松(DEX;临床相关的治疗剂)的吸收,从而将药物含量提高至0.5 mg / mL(颗粒中10 wt%) )。此外,此类纳米蠕虫可稳定至少5个月,因此是纳米医学应用的有前途的平台。具有已知对流动行为和与细胞相互作用具有深远影响的细长形式。卸载的纳米蠕虫对人视网膜(ARPE-19)细胞无毒,即使在改变表面电荷后也可以被有效地内吞。在药物载量方面,我们证明了使用该方法可以增强纳米蠕虫(DEX @ NWs)中地塞米松(DEX;临床相关的治疗剂)的吸收,从而将药物含量提高至0.5 mg / mL(颗粒中10 wt%) )。此外,此类纳米蠕虫可稳定至少5个月,因此是纳米医学应用的有前途的平台。具有已知对流动行为和与细胞相互作用具有深远影响的细长形式。卸载的纳米蠕虫对人视网膜(ARPE-19)细胞无毒,即使在改变表面电荷后也可以被有效地内吞。在药物载量方面,我们证明了使用该方法可以增强纳米蠕虫(DEX @ NWs)中地塞米松(DEX;临床相关的治疗剂)的吸收,从而将药物含量提高至0.5 mg / mL(颗粒中10 wt%) )。此外,此类纳米蠕虫可稳定至少5个月,因此是纳米医学应用的有前途的平台。可以使用此过程增强纳米蠕虫(DEX @ NWs)中的临床相关治疗剂),将药物含量提高到0.5 mg / mL(颗粒中为10 wt%)。此外,此类纳米蠕虫可稳定至少5个月,因此是纳米医学应用的有前途的平台。可以使用此过程增强纳米蠕虫(DEX @ NWs)中的临床相关治疗剂),将药物含量提高到0.5 mg / mL(颗粒中为10 wt%)。此外,此类纳米蠕虫可稳定至少5个月,因此是纳米医学应用的有前途的平台。
更新日期:2020-03-25
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