Chinese Journal of Tissue Engineering Research ›› 2018, Vol. 22 ›› Issue (14): 2190-2194.doi: 10.3969/j.issn.2095-4344.0748
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Peng Xu-feng1, 2, Luo Wen-qiang1, 2, Zhang Xin-ru1, 2, Wang Ji-hong1, 2
Received:
2017-12-09
Online:
2018-05-18
Published:
2018-05-18
Contact:
Wang Ji-hong, M.D., Department of Urology, Shanghai Sixth People’s Hospital of Shanghai Jiao Tong University, Shanghai 200233, China
About author:
Peng Xu-feng, Master candidate, Department of Urology, Shanghai Sixth People’s Hospital of Shanghai Jiao Tong University, Shanghai 200233, China
CLC Number:
Peng Xu-feng, Luo Wen-qiang, Zhang Xin-ru, Wang Ji-hong. Preparation and physicochemical characterization of levofloxacin-loaded poly(lactic-co-glycolic acid) nanoparticles[J]. Chinese Journal of Tissue Engineering Research, 2018, 22(14): 2190-2194.
2.1 实验动物数量分析 共纳入新西兰大白兔69只,有1只因感染而死于败血症未补充,未纳入结果分析。 2.2 左氧氟沙星PLGA纳米微球的鉴定 采用乳化溶剂挥发法,以二氯甲烷为溶剂相,PLGA为载体相,左氧氟沙星为包埋对象,聚乙烯醇为乳化剂成功制备了基于PLGA不同批次的左氧氟沙星纳米微球。在制作过程中采用单因素变量法探讨多种因素对纳米微球直径大小、载药量、包封率的影响(表1,图1,2),包括PLGA的组成、PLGA相对分子质量的大小、内外部水相比PLGA的浓度。从图1C可见当乳酸/羟基乙酸比为60/40,50/50时累计释放曲线呈现典型的三段式,当组成比为70/30,80/20,90/10时,PLGA纳米微球有早期的突然释放和之后趋于平稳的缓释,考虑到初始用药需尽早达到药物的有效抑菌溶度和后期的维持时间,当比例为80/20时是最为理想的组成。从图2a,b,c结合表1可见,当PLGA的相对分子质量为38 000,浓度为20%,内外部水相比为3∶5能够保证PLGA纳米微球中的左氧氟沙星载药量达到较高的同时包封率较高且缓释性能达到最佳,故以此条件下的PLGA纳米微球进行后续实验。"
2.4 左氧氟沙星PLGA纳米微球的体内药代动力学特性 通过高效液相色谱法分析发现,最优条件下的左氧氟沙星PLGA纳米微球其平均载药量为(13.2±0.6)%,包封率为88.9%。体内药代动力学研究表明,传统剂型的左氧氟沙星在静脉应用后能迅速达到血药浓度的峰值为(3.8± 1.2) mg/L,其消除相半衰期约为13 h,约2 d基本已完全从 体内代谢消失。而左氧氟沙星PLGA纳米微球在应用后血药浓度逐步升高,并达到峰值(3.6±1.3)mg/L,之后逐步稳定能维持在质量浓度2 mg/L以上约12 d,最终逐步下降,30 d后从体内基本无法检出(图2d)。 2.5 左氧氟沙星PLGA纳米微球的抗菌性能评估 不同时间点尿中大肠杆菌阳性率的比较:见表2。制模前各组动物菌尿阳性率均为阴性,造模后菌尿阳性率达100%,说明建模成功。开始用药后,传统剂型组和纳米微球组抑菌作用逐步显现,到用药的第5天,两组与空白对照组差异有显著性意义,且一直延续到第9天,其中在第5天时传统剂型组与纳米微球组之间差异有显著性意义(P < 0.05)。 不同时间点尿中白细胞阳性率的比较:见表2。制模前各组动物尿白细胞阳性率均为阴性,造模后菌尿阳性率达100%。用药后第3天纳米微球组阳性率开始下降,传统剂型组阳性率第5天开始下降,一直持续到第9天。"
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