School of Pharmacy, China Medical University, Shenyang, 110122, PR China; School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, PR China.
School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, PR China.
Colloids Surf B Biointerfaces. 2021 Mar;199:111501. doi: 10.1016/j.colsurfb.2020.111501. Epub 2020 Dec 4.
This study examined the effects of pH and chirality on the release of flurbiprofen (FP)-loaded chiral (L/D) self-assembled mesoporous silica nanoparticles (CSA-L/D-MSNs), which were synthesized using cationic cetyltrimethyl ammonium bromide (CTAB) as a template and chiral modified using L/D-tartaric acids. The morphology and physicochemical properties of the CSA-L/D-MSNs were systemically determined and compared with those of non-functionalized mesoporous silica nanoparticles (MSN). The results showed that the CSA-L/D-MSNs were spherical nanoparticles, and the chirality in the L/D-tartaric acids was successfully imparted to the CSA-L/D-MSNs. FP could be loaded into the CSA-L/D-MSNs and was effectively transformed from the crystalline state to an amorphous state after drug loading due to the finite size effect. The release of FP@CSA-L/D-MSNs was faster than that of FP in a pH 1.2 medium and slower in a pH 6.8 medium, and it was better than that of FP@MSNs in both release mediums. Meanwhile, the FP@CSA-L/D-MSNs exhibited a clearly enhanced pH response because the negatively charged carboxyl groups on their surface induced stronger electrostatic repulsion between FP and CSA-L/D-MSNs. Moreover, the effect of the chiral environment on the release of FP@CSA-L/D-MSNs was further studied by introducing small-molecule chiral additives (L/D-alanine). It was found that the release of FP was inhibited in a chiral environment. Particularly, the CSA-L/D-MSNs began to exert the chiral recognition function, in which the CSA-L-MSN responded to chiral stimuli and enhanced the cumulative release amount from 84.25 %-89.11 % in a pH 6.8-L medium, while the CSA-D-MSN showed a suppressed release in the pH 6.8-L medium. Notably, the CSA-L/D-MSNs exhibited intelligent drug release by both chirality response and pH response, and will provide valuable guidance for the design of drug delivery systems.
本研究考察了 pH 值和手性对负载氟比洛芬（FP）的手性（L/D）自组装介孔硅纳米粒子（CSA-L/D-MSNs）释放的影响，这些纳米粒子是使用阳离子十六烷基三甲基溴化铵（CTAB）作为模板并使用 L/D-酒石酸进行手性修饰合成的。系统地测定和比较了 CSA-L/D-MSNs 的形态和物理化学性质与非功能化介孔硅纳米粒子（MSN）的性质。结果表明，CSA-L/D-MSNs 呈球形纳米粒子，并且 L/D-酒石酸中的手性成功地赋予了 CSA-L/D-MSNs。FP 可以负载到 CSA-L/D-MSNs 中，并且由于有限的尺寸效应，在药物负载后，FP 可以从结晶态有效地转变为无定形态。在 pH 1.2 介质中，FP@CSA-L/D-MSNs 的释放速度比 FP 快，在 pH 6.8 介质中释放速度较慢，在两种释放介质中均优于 FP@MSNs。同时，FP@CSA-L/D-MSNs 表现出明显增强的 pH 响应，因为其表面带负电荷的羧基基团导致 FP 和 CSA-L/D-MSNs 之间产生更强的静电排斥。此外，通过引入小分子手性添加剂（L/D-丙氨酸）进一步研究了手性环境对 FP@CSA-L/D-MSNs 释放的影响。结果发现，FP 的释放在手性环境中受到抑制。特别是，CSA-L/D-MSNs 开始发挥手性识别功能，其中 CSA-L-MSN 对手性刺激做出响应并增强了在 pH 6.8-L 介质中的累积释放量，从 84.25%-89.11%，而 CSA-D-MSN 在 pH 6.8-L 介质中表现出抑制释放。值得注意的是，CSA-L/D-MSNs 通过手性响应和 pH 响应表现出智能药物释放，这将为药物传递系统的设计提供有价值的指导。
