Gholami Mitra, Mohammadi Rashin, Arzanlou Mohsen, Akbari Dourbash Fakhraddin, Kouhsari Ebrahim, Majidi Gharib, Mohseni Seyed Mohsen, Nazari Shahram
Department of Environmental Health Engineering, School of public Health, Iran University of Medical Sciences, Tehran, Iran.
Department of Life Science Engineering, Faculty of New Science and Technology, University of Tehran, Tehran, Iran.
BMC Infect Dis. 2017 Jun 5;17(1):395. doi: 10.1186/s12879-017-2513-7.
Nano-scale dendrimers are synthetic macromolecules that frequently used in medical and health field. Traditional anibiotics are induce bacterial resistence so there is an urgent need for novel antibacterial drug invention. In the present study seventh generation poly (amidoamine) (PAMAM-G7) dendrimer was synthesized and its antibacterial activities were evaluated against representative Gram- negative and Gram-positive bacteria.
PAMAM-G7 was synthesized with divergent growth method. The structural and surface of PAMAM-G7 were investigated by transmission electron microscopy, scanning electron microscope and fourier transform infrared. Pseudomonas. aeruginosa (n = 15), E. coli (n = 15), Acinetobacter baumanni (n = 15), Shigella dysenteriae (n = 15), Klebsiella pneumoniae (n = 10), Proteus mirabilis (n = 15), Staphylococcus aureus (n = 15) and Bacillus subtilis (n = 10) have been used for antibacterial activity assay. Additionally, representative standard strains for each bacterium were included. Minimum Inhibitory Concentration (MIC) was determined using microdilution method. Subsequently, Minimum Bactericidal Concentration (MBC) was determined by sub-culturing each of the no growth wells onto Mueller Hinton agar medium. The cytotoxicity of PAMAM-G7 dendrimer were evaluated in HCT116 and NIH 3 T3 cells by MTT assay.
The average size of each particle was approximately 20 nm. PAMAM-G7 was potentially to inhibit both Gram positive and gram negative growth. The MIC50 and MIC90 values were determined to be 2-4 μg/ml and 4-8 μg/ml, respectively. The MBC50 and MBC90 values were found to be 64-256 μg/ml and 128-256 μg/ml, respectively. The cytotoxity effect of dendrimer on HCT116 and NIH 3 T3 cells is dependent upon exposure time to and concentration of dendrimers. The most reduction (44.63 and 43%) in cell viability for HCT116 and NIH 3 T3 cells was observed at the highest concentration, 0.85 μM after 72 h treatmentm, respectively.
This study we conclude that PAMAM-G7 dendrimer could be a potential candidate as a novel antibacterial agent.
纳米级树枝状大分子是常用于医疗保健领域的合成大分子。传统抗生素会诱导细菌产生耐药性，因此迫切需要发明新型抗菌药物。在本研究中，合成了第七代聚（酰胺胺）（PAMAM-G7）树枝状大分子，并评估了其对代表性革兰氏阴性菌和革兰氏阳性菌的抗菌活性。
采用发散生长法合成PAMAM-G7。通过透射电子显微镜、扫描电子显微镜和傅里叶变换红外光谱对PAMAM-G7的结构和表面进行了研究。使用铜绿假单胞菌（n = 15）、大肠杆菌（n = 15）、鲍曼不动杆菌（n = 15）、痢疾志贺菌（n = 15）、肺炎克雷伯菌（n = 10）、奇异变形杆菌（n = 15）、金黄色葡萄球菌（n = 15）和枯草芽孢杆菌（n = 10）进行抗菌活性测定。此外，每种细菌均包含代表性标准菌株。采用微量稀释法测定最低抑菌浓度（MIC）。随后，通过将每个无生长孔的菌液接种到 Mueller Hinton 琼脂培养基上，测定最低杀菌浓度（MBC）。通过 MTT 法评估 PAMAM-G7 树枝状大分子在 HCT116 和 NIH 3T3 细胞中的细胞毒性。
每个颗粒的平均大小约为20nm。PAMAM-G7 有可能抑制革兰氏阳性菌和革兰氏阴性菌的生长。MIC50 和 MIC90 值分别测定为2-4μg/ml 和 4-8μg/ml。MBC50 和 MBC90 值分别为64-256μg/ml 和 128-256μg/ml。树枝状大分子对 HCT116 和 NIH 3T3 细胞的细胞毒性作用取决于与树枝状大分子的接触时间和浓度。在最高浓度0.85μM、处理72小时后，HCT116 和 NIH 3T3 细胞的细胞活力分别出现最大程度的降低（44.63%和 43%）。
本研究得出结论，PAMAM-G7 树枝状大分子可能是一种新型抗菌剂的潜在候选物。
