Zhang Meng, Yu Zhiyi, Lo Edward Chin Man
Faculty of Dentistry, The University of Hong Kong, Pok Fu Lam, Hong Kong, SAR China.
Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China.
Front Microbiol. 2021 Oct 18;12:761583. doi: 10.3389/fmicb.2021.761583. eCollection 2021.
The bactericidal effect on biofilm is the main challenge currently faced by antibacterial agents. Nanoscale drug-delivery materials can enhance biofilm penetrability and drug bioavailability, and have significant applications in the biomedical field. Dental caries is a typical biofilm-related disease, and the acidification of biofilm pH is closely related to the development of dental caries. In this study, a pH-responsive core-shell nano micelle (mPEG-b-PDPA) capable of loading hydrophobic antibacterial agents was synthesized and characterized, including its ability to deliver antibacterial agents within an acidic biofilm. The molecular structure of this diblock copolymer was determined by hydrogen-1 nuclear magnetic resonance (H-NMR) and gel permeation chromatography (GPC). The characters of the micelles were studied by dynamic light scattering (DLS), TEM, pH titration, and drug release detection. It was found that the hydrophilic micelles could deliver bedaquiline, a hydrophobic antibacterial agent on , in acidic environments and in mature biofilm. No cytotoxic effect on the periodontal cells was detected within 48 h. This pH-responsive micelle, being able to load hydrophobic antibacterial agent, has good clinical application potential in preventing dental caries.
对生物膜的杀菌作用是目前抗菌剂面临的主要挑战。纳米级药物递送材料可增强生物膜渗透性和药物生物利用度，在生物医学领域有重要应用。龋齿是一种典型的生物膜相关疾病，生物膜pH值的酸化与龋齿的发展密切相关。在本研究中，合成并表征了一种能够负载疏水性抗菌剂的pH响应性核壳纳米胶束（mPEG-b-PDPA），包括其在酸性生物膜内递送抗菌剂的能力。通过氢-1核磁共振（H-NMR）和凝胶渗透色谱（GPC）确定了这种二嵌段共聚物的分子结构。通过动态光散射（DLS）、透射电子显微镜（TEM）、pH滴定和药物释放检测研究了胶束的特性。结果发现，亲水性胶束能够在酸性环境和成熟生物膜中递送疏水性抗菌剂贝达喹啉。在48小时内未检测到对牙周细胞的细胞毒性作用。这种能够负载疏水性抗菌剂的pH响应性胶束在预防龋齿方面具有良好的临床应用潜力。
