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pH 依赖性载氯己定 PGA 接枝介孔硅纳米颗粒在树脂-牙本质界面的释放。

pH-dependent delivery of chlorhexidine from PGA grafted mesoporous silica nanoparticles at resin-dentin interface.

机构信息

UWA Dental School, University of Western Australia, 17 Monash Avenue, Nedlands, WA, 6009, Australia.

出版信息

J Nanobiotechnology. 2021 Feb 9;19(1):43. doi: 10.1186/s12951-021-00788-6.

Abstract

BACKGROUND

A low pH environment is created due to the production of acids by oral biofilms that further leads to the dissolution of hydroxyapatite crystal in the tooth structure significantly altering the equilibrium. Although the overall bacterial counts may not be eradicated from the oral cavity, however, synthesis of engineered anti-bacterial materials are warranted to reduce the pathogenic impact of the oral biofilms. The purpose of this study was to synthesize and characterize chlorhexidine (CHX)-loaded mesoporous silica nanoparticles (MSN) grafted with poly-L-glycolic acid (PGA) and to test the in vitro drug release in various pH environments, cytotoxicity, and antimicrobial capacity. In addition, this study aimed to investigate the delivery of CHX-loaded/MSN-PGA nanoparticles through demineralized dentin tubules and how these nanoparticles interact with tooth dentin after mixing with commercial dentin adhesive for potential clinical application.

RESULTS

Characterization using SEM/TEM and EDX confirmed the synthesis of CHX-loaded/MSN-PGA. An increase in the percentage of drug encapsulation efficiency from 81 to 85% in CHX loaded/MSN and 92-95% in CHX loaded/MSN-PGA proportionately increased with increasing the amount of CHX during the fabrication of nanoparticles. For both time-periods (24 h or 30 days), the relative microbial viability significantly decreased by increasing the CHX content (P < 0.001). Generally, the cell viability percentage of DPSCs exposed to MSN-PGA/Blank, CHX-loaded/MSN, and CHX-loaded/MSN-PGA, respectively was > 80% indicating low cytotoxicity profiles of experimental nanoparticles. After 9 months in artificial saliva (pH 7.4), the significantly highest micro-tensile bond strength value was recorded for 25:50 CHX/MSN and 25:50:50 CHX/MSN-PGA. A homogenous and widely distributed 50:50:50 CHX-loaded/MSN-PGA nanoparticles exhibited excellent bonding with the application of commercially available dentin adhesive.

CONCLUSIONS

A pH-sensitive CHX release response was noted when loaded in MSN grafted PGA nanoparticles. The formulated drug-loaded nanocarrier demonstrated excellent physicochemical, spectral, and biological characteristics. Showing considerable capacity to penetrate effectively inside dentinal tubules and having high antibacterial efficacy, this system could be potentially used in adhesive and restorative dentistry.

摘要

背景

口腔生物膜产生的酸会导致环境 pH 值降低,进而显著改变牙齿结构中羟磷灰石晶体的平衡,导致其溶解。尽管口腔中的总细菌计数可能无法完全消除,但合成工程抗菌材料对于降低口腔生物膜的致病影响是必要的。本研究的目的是合成并表征负载氯己定(CHX)的介孔硅纳米粒子(MSN)接枝聚 L-丙交酯(PGA),并在不同 pH 值环境下测试体外药物释放、细胞毒性和抗菌能力。此外,本研究旨在研究 CHX 负载/MSN-PGA 纳米粒子通过脱矿牙本质小管的输送方式,以及这些纳米粒子与商业牙本质黏合剂混合后与牙本质的相互作用,以期为临床应用提供参考。

结果

SEM/TEM 和 EDX 分析证实了 CHX 负载/MSN-PGA 的合成。随着纳米粒制备过程中 CHX 用量的增加,CHX 负载/MSN 中药物包封效率从 81%增加到 85%,CHX 负载/MSN-PGA 中药物包封效率从 92%增加到 95%。对于两个时间段(24 小时或 30 天),随着 CHX 含量的增加,相对微生物活力显著降低(P<0.001)。通常,暴露于 MSN-PGA/空白、CHX 负载/MSN 和 CHX 负载/MSN-PGA 的 DPSCs 的细胞活力百分比均大于 80%,表明实验纳米粒子的细胞毒性较低。在人工唾液(pH7.4)中放置 9 个月后,25:50 CHX/MSN 和 25:50:50 CHX/MSN-PGA 的微拉伸结合强度值记录值最高。均匀且广泛分布的 50:50:50 CHX 负载/MSN-PGA 纳米粒子与市售牙本质黏合剂的应用具有出色的结合能力。

结论

当负载在接枝 PGA 的 MSN 中时,观察到 CHX 释放具有 pH 敏感性。所构建的载药纳米载体表现出优异的物理化学、光谱和生物学特性。该系统具有较强的穿透牙本质小管的能力,具有较高的抗菌效果,可潜在应用于黏结和修复牙科。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25fb/7871398/f10c8407b35a/12951_2021_788_Fig1_HTML.jpg

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