Ramteke Suman, Ganesh N, Bhattacharya S, Jain Narendra K
School of Pharmaceutical Sciences, Rajiv Gandhi Technical University, Bhopal, India.
J Drug Target. 2008 Nov;16(9):694-705. doi: 10.1080/10611860802295839.
The main aim of drug targeting was to increase the selectivity and efficacy of drugs at the infected site and to reduce the toxicity of biotechnological entities on other parts of the body. In the present study, we selected the triple therapy (amoxicillin, clarithromycin and omeprazole) due to its synergic and additive effects, which could drastically reduce the effective dose required for the complete eradication of Helicobacter pylori and prevent the development of antibiotic resistance. The gliadin nanoparticles (GNP) vis-à-vis lectin-conjugated gliadin nanoparticles (LGNP) of triple therapy were prepared by a desolvation method and evaluated for percent entrapment efficiency, percent yield, in vitro drug release study and mucoadhesion properties of formulations. The maximum percent entrapment efficiency of formulations was in the range of 65-85%. The percent yield of formulation was about 84 +/- 2.68%. The maximum percent cumulative release of all the three drugs from formulations was in the range of 22-76%. The specificity of lectin-conjugated particles was assessed by an in vitro agglutination assay method. The developed formulation was also assessed for in vitro antibacterial study, in vivo clearance efficacy and histopathological evaluation of formulations. In the in vitro antibacterial study, the LGNP with triple therapy showed a 94.83% eradication rate that is 7.4% more than that of GNP with triple therapy (88.28%) and about 16% more than that of the plain triple therapy (P < 0.001). The targeted lectin-conjugated formulations exhibited a superior in vivo clearance efficacy when compared to the non-conjugated formulations and plain drugs.
药物靶向的主要目的是提高药物在感染部位的选择性和疗效,并降低生物技术实体对身体其他部位的毒性。在本研究中,我们选择三联疗法(阿莫西林、克拉霉素和奥美拉唑),因其具有协同和相加作用,可大幅降低完全根除幽门螺杆菌所需的有效剂量,并防止抗生素耐药性的产生。通过去溶剂化方法制备了三联疗法的麦醇溶蛋白纳米颗粒(GNP)和凝集素共轭麦醇溶蛋白纳米颗粒(LGNP),并对制剂的包封率、产率、体外药物释放研究和粘膜粘附特性进行了评估。制剂的最大包封率在65 - 85%范围内。制剂的产率约为84±2.68%。所有三种药物从制剂中的最大累积释放率在22 - 76%范围内。通过体外凝集试验方法评估凝集素共轭颗粒的特异性。还对所开发的制剂进行了体外抗菌研究、体内清除效果和组织病理学评估。在体外抗菌研究中,三联疗法的LGNP显示出94.83%的根除率,比三联疗法的GNP(88.28%)高7.4%,比单纯三联疗法高约16%(P < 0.001)。与未共轭制剂和普通药物相比,靶向凝集素共轭制剂在体内清除效果方面表现更优。