Ionic-Liquid-Modified Nanoparticles as Potential Mucus Modulators for Nasal Drug Delivery
Ionic-Liquid-Modified Nanoparticles as Potential Mucus Modulators for Nasal Drug Delivery
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离子液体修饰纳米颗粒作为鼻腔药物输送的潜在粘液调节剂
DOI：
10.1021/acsanm.3c03807
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发表时间：
2023
影响因子：
5.9
通讯作者：
Tanner, Eden E.
中科院分区：
文献类型：
--
作者：
VanLandingham, Mary E.;Heintz, Rebekah A.;Kariyawasam, Chathuri S.;Darlington, Donovan S.;Chism, Claylee M.;Edgecomb, Sara X.;Roberts, Angela;Marzette, Jorden;Fitzkee, Nicholas C.;Tanner, Eden E.
粘液屏障是一种天然的防御系统，用于防止异物进入体内;然而，它们对有效的药物递送构成障碍。与其未涂覆的或裸露的对应物相比，涂覆的聚合物纳米颗粒（NP）已经显示出具有改善的穿过粘液的扩散速率。基于胆碱羧酸的离子液体（IL）是高度可调的，并且显示出高生物相容性和粘液调节特性，使其成为改善NP通过粘膜屏障扩散的理想选择。本研究旨在通过使用多颗粒跟踪方法研究使用基于胆碱的IL是否对聚（乳酸-乙醇酸）（PLGA）、聚（乙二醇）甲基醚-嵌段-聚（丙交酯-乙交酯）（PEG-PLGA）和聚（乙二醇）-聚（乳酸）（PEG-PLA）NPs通过鼻粘液的粘附具有积极作用。根据所用的IL，样品在水性和粘膜环境中的扩散速率均发生改变。CA 2 HE 1：1与PEG-PLGA NP的使用减慢了NP扩散，而相同IL的使用增加了PEG-PLA的扩散。此外，使用紫外-可见光谱来鉴定粘蛋白聚合物和NP之间可能形成的复合物。圆二色性（CD）光谱用于分析由于引入聚合物NP而导致的粘蛋白二级结构的任何潜在变化。已经证明，使用IL可以稳定聚合物NP和粘蛋白聚合物之间的相互作用。等温滴定量热法用于获得NP和粘液之间的结合能的定量测量，并用于确认从CD光谱获得的结果。最后，使用离体猪鼻粘膜模型来探索它们在鼻递送环境中的用途，揭示了两性离子转运材料的使用与更有效的药物递送之间的可能联系。这项研究证明了基于胆碱羧酸的离子液体控制用于鼻内药物递送的聚合物纳米颗粒的转运行为的潜力。
Mucosal barriers are a natural defense system for preventing the entry of foreign objects into the body; however, they pose obstacles for effective drug delivery. Coated polymer nanoparticles (NPs) have been shown to possess improved rates of diffusion across mucus compared to their uncoated, or bare, counterparts. Choline carboxylic acid-based ionic liquids (ILs) are highly tunable and show high biocompatibility and mucus modulation properties, making them an ideal choice for the improvement of NP diffusion through mucosal barriers. This study aimed to investigate whether the use of choline-based ILs has a positive effect on the dispersibility of poly(lactic-co-glycolic acid) (PLGA), poly(ethylene glycol) methyl ether-block-poly(lactide-co-glycolide) (PEG–PLGA), and poly(ethylene glycol)–poly(lactic acid) (PEG–PLA) NPs through nasal mucus by using a multiple particle tracking method. The samples, according to the IL used, showed altered rates of diffusion in both aqueous and mucosal environments. The use of CA2HE 1:1 with PEG–PLGA NPs slowed NP diffusion, while the use of the same IL increased diffusion for PEG–PLA. Additionally, UV–vis spectroscopy was used to identify the possible formation of complexes between the mucin polymer and NPs. Circular dichroism (CD) spectroscopy was used to analyze any potential changes in the secondary structure of mucin as a result of the introduction of polymeric NPs. It was demonstrated that the use of an IL can stabilize the interactions between polymer NPs and mucin polymers. Isothermal titration calorimetry was used to obtain quantitative measurement of the binding energies between NPs and mucus and serves to confirm the results obtained from CD spectroscopy. Last, an ex vivo porcine nasal mucosa model was used to explore their use in a nasal delivery context, disclosing a possible connection between the use of zwitterionic transport materials and more effective drug delivery. This research demonstrates the potential of choline carboxylic acid-based ILs to control the transport behavior of polymer NPs for intranasal drug delivery.
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影响因子：
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影响因子：
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影响因子：
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