Alqahtani Fulwah Y, Aleanizy Fadilah S, El Tahir Eram, Alowais Hessa, Binkelaib Assalh, Alwathlan Bdour, Al-Bdrawy Asmaa, Håkansson Anders P, Alsarra Ibrahim
Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11495, Saudi Arabia.
Department of Translational Medicine, Division of Experimental Infection Medicine, Lund University, SE-21428 Malmö, Sweden.
Polymers (Basel). 2021 Aug 30;13(17):2924. doi: 10.3390/polym13172924.
remains a major cause of community-acquired pneumonia, meningitis, and other diseases, contributing significantly to high morbidity and mortality worldwide. Although it responds to antibiotics, their use is becoming limited due to the rise in antibiotic resistance, which necessitates the development of new therapeutics. Nanotechnology is used to counteract antimicrobial resistance. In this regard, polymeric nanoparticles (NPs) made of natural, biodegradable, biocompatible, and cationic polymers such as Chitosan (CNPs) exhibit wide-spectrum antimicrobial activity. Therefore, this study aimed to prepare CNPs, characterize their physiochemical characteristics: particle size (PZ), polydispersity index (PDI), and zeta potential (ZP), and investigate their antimicrobial activity against TIGR4 (virulent serotype 4) and its capsular mutant (∆cps).
CNPs were prepared at 1, 2.5, and 5 mg/mL concentrations using the ion gelation method. Then, PZ, PDI, and ZP were characterized using a Zetasizer. Transmission electron microscopy (TEM) was used to visualize the CNP's morphology. Broth and agar dilution methods were used to assess their antimicrobial activity. Cytotoxicity of prepared NPs on A549 cells and their effect on pneumococcal hemolysis were also investigated.
Spherical CNPs were produced with PZ ranging from 133.3 nm ± 0.57 to 423 nm ± 12.93 PDI < 0.35, and ZP from 19 ± 0.115 to 27 ± 0.819. The prepared CNPs exhibited antibacterial activity against TIGR4 and its capsule mutant with a minimum inhibitory concentration (MIC90) of 0.5 to 2.5 mg/mL in a non-acidic environment. The hemolysis assay results revealed that CNPs reduced bacterial hemolysis in a concentration-dependent manner. Their mammalian cytotoxicity results indicated that CNPs formed from low concentrations of Chitosan (Cs) were cytocompatible.
Nanochitosan particles showed anti-pneumococcal activity regardless of the presence of capsules. They resulted in a concentration-dependent reduction in bacterial hemolysis and were cytocompatible at a lower concentration of Cs. These findings highlight the potential of CNPs in the treatment of pneumococcal diseases.
仍是社区获得性肺炎、脑膜炎和其他疾病的主要病因，在全球范围内导致了高发病率和高死亡率。尽管它对抗生素有反应，但由于抗生素耐药性的增加，抗生素的使用正变得受限，这就需要开发新的治疗方法。纳米技术被用于对抗抗菌耐药性。在这方面，由天然、可生物降解、生物相容且带阳离子的聚合物（如壳聚糖）制成的聚合物纳米颗粒（NPs）表现出广谱抗菌活性。因此，本研究旨在制备壳聚糖纳米颗粒，表征其物理化学特性：粒径（PZ）、多分散指数（PDI）和zeta电位（ZP），并研究其对TIGR4（强毒株血清型4）及其荚膜突变体（∆cps）的抗菌活性。
使用离子凝胶法以1、2.5和5 mg/mL的浓度制备壳聚糖纳米颗粒。然后，使用Zetasizer对PZ、PDI和ZP进行表征。透射电子显微镜（TEM）用于观察壳聚糖纳米颗粒的形态。采用肉汤稀释法和琼脂稀释法评估其抗菌活性。还研究了制备的纳米颗粒对A549细胞的细胞毒性及其对肺炎球菌溶血的影响。
制备出了球形壳聚糖纳米颗粒，其粒径范围为133.3 nm±0.57至423 nm±12.93，多分散指数小于0.35，zeta电位为19±0.115至27±0.819。在非酸性环境中，制备的壳聚糖纳米颗粒对TIGR4及其荚膜突变体表现出抗菌活性，最低抑菌浓度（MIC90）为0.5至2.5 mg/mL。溶血试验结果表明，壳聚糖纳米颗粒以浓度依赖的方式降低了细菌溶血。其对哺乳动物的细胞毒性结果表明，由低浓度壳聚糖（Cs）形成的壳聚糖纳米颗粒具有细胞相容性。
无论是否存在荚膜，纳米壳聚糖颗粒均显示出抗肺炎球菌活性。它们导致细菌溶血呈浓度依赖性降低，并且在较低浓度的壳聚糖下具有细胞相容性。这些发现突出了壳聚糖纳米颗粒在治疗肺炎球菌疾病方面的潜力。
