School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast, BT9 7BL, Northern Ireland, UK.
Pharm Res. 2013 Mar;30(3):857-65. doi: 10.1007/s11095-012-0927-x. Epub 2012 Nov 15.
The pH-dependent physicochemical properties of the antimicrobial quinolone, nalidixic acid, were exploited to achieve 'intelligent' drug release from a potential urinary catheter coating, poly(2-hydroxyethylmethacrylate) (p(HEMA)), in direct response to the elevated pH which occurs at the onset of catheter infection.
p(HEMA) hydrogels, and reduced-hydrophilicity copolymers incorporating methyl methacrylate, were loaded with nalidixic acid by a novel, surface particulate localization method, and characterized in terms of pH-dependent drug release and microbiological activity against the common urease-producing urinary pathogen Proteus mirabilis.
The pH-dependent release kinetics of surface-localized nalidixic acid were 50- and 10-fold faster at pH 9, representing the alkaline conditions induced by urease-producing urinary pathogens, compared to release at pH 5 and pH 7 respectively. Furthermore, microbiological activity against P. mirabilis was significantly enhanced after loading surface particulate nalidixic acid in comparison to p(HEMA) hydrogels conventionally loaded with dispersed drug. The more hydrophobic methyl methacrylate-containing copolymers also demonstrated this pH-responsive behavior, but additionally exhibited a sustained period of zero-order release.
The paradigm presented here provides a system with latent, immediate infection-responsive drug release followed by prolonged zero-order antimicrobial delivery, and represents an 'intelligent', infection-responsive, self-sterilizing biomaterial.
利用抗菌喹诺酮类药物萘啶酸的 pH 依赖性物理化学性质，实现在潜在的尿液导管涂层聚（2-羟乙基甲基丙烯酸酯）（p（HEMA））中“智能”药物释放，直接响应导管感染开始时出现的升高 pH 值。
通过一种新颖的表面颗粒定位方法将 p（HEMA）水凝胶和含有甲基丙烯酸甲酯的低亲水性共聚物负载萘啶酸，并根据 pH 依赖性药物释放和对常见产脲酶尿路病原体奇异变形杆菌的微生物活性进行表征。
与在 pH 5 和 pH 7 时的释放相比，在 pH 9 时表面定位的萘啶酸的 pH 依赖性释放动力学分别快 50 倍和 10 倍，代表由产脲酶的尿路病原体诱导的碱性条件。此外，与常规负载分散药物的 p（HEMA）水凝胶相比，负载表面颗粒萘啶酸后对奇异变形杆菌的微生物活性显著增强。含有疏水性甲基丙烯酸甲酯的共聚物也表现出这种 pH 响应行为，但此外还表现出持续的零级释放期。
这里提出的范例提供了一种具有潜伏的、即时感染响应性药物释放的系统，随后是延长的零级抗菌药物输送，代表了一种“智能”、感染响应性、自消毒生物材料。
