School of Pharmacy, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, UK.
J Photochem Photobiol B. 2012 Sep 3;114:61-72. doi: 10.1016/j.jphotobiol.2012.05.011. Epub 2012 May 24.
The loading of the photosensitisers meso-Tetra (N-methyl-4-pyridyl) porphine tetra tosylate (TMP), methylene blue (MB) and TMP with sodium dodecyl sulphate (SDS) into and release from hydrogels composed of the polyelectrolyte poly(methyl vinyl ether-co-maleic acid) crosslinked in a 2:1 ratio with PEG 10,000 were investigated as a potential rapid photodynamic antimicrobial chemotherapy (PACT) treatment for infected wounds using iontophoresis as a novel delivery method. Photosensitiser uptake was very high; (% TMP uptake; 95.53-96.72%) (% MB uptake; 90.58-93.26%) and was PMVE/MA concentration independent, whilst SDS severely limited TMP uptake (5.93-8.75%). Hydrogel hardness, compressibility and adhesiveness on the dermal surface of neonate porcine skin increased with PMVE/MA concentration and were significantly increased with SDS. The ionic conductivities of the hydrogels increased with PMVE/MA concentration. Drug release was PMVE/MA concentration independent, except for drug release under iontophoteric conditions for MB and TMP (without SDS). In just 15 min, the mean% drug concentrations released of TMP, TMP (with SDS) and MB using an electric current ranged from 22.30 to 64.72 μg ml(-1), 6.37-4.59 μg ml(-1) and 11.73-36.57 μg ml(-1) respectively. These concentrations were in excess of those required to induce complete kill of clinical strains of meticillin-resistant Staphylococcus aureus and Burkholderia cepacia. Thus these results support our contention that the iontophoteric delivery of TMP and MB using anti-adherent, electrically-responsive, PEG-crosslinked PMVE/MA hydrogels are a potential option in the rapid PACT treatment of infected wounds.
将光敏剂间四(N-甲基-4-吡啶基)卟啉四对甲苯磺酸盐(TMP)、亚甲蓝(MB)和 TMP 与十二烷基硫酸钠(SDS)载入并释放到由聚电解质聚(甲基乙烯基醚-马来酸)与聚乙二醇 10,000 以 2:1 的比例交联而成的水凝胶中,用作感染伤口的快速光动力抗菌化疗(PACT)治疗的潜在方法,离子电渗法作为一种新的输送方法。光敏剂摄取量非常高;(TMP 摄取量的%;95.53-96.72%)(MB 摄取量的%;90.58-93.26%),且与 PMVE/MA 浓度无关,而 SDS 严重限制 TMP 的摄取(5.93-8.75%)。水凝胶的硬度、压缩性和在新生仔猪皮肤真皮表面的粘性随 PMVE/MA 浓度增加而增加,并随 SDS 显著增加。水凝胶的离子电导率随 PMVE/MA 浓度增加。药物释放与 PMVE/MA 浓度无关,除了在 MB 和 TMP (无 SDS)的离子电渗条件下的药物释放。在 15 分钟内,使用电流释放的 TMP、TMP(含 SDS)和 MB 的平均%药物浓度范围分别为 22.30-64.72μgml(-1)、6.37-4.59μgml(-1)和 11.73-36.57μgml(-1)。这些浓度超过了诱导耐甲氧西林金黄色葡萄球菌和洋葱伯克霍尔德菌临床株完全杀灭所需的浓度。因此,这些结果支持我们的论点,即使用抗附着、电响应、PEG 交联 PMVE/MA 水凝胶进行 TMP 和 MB 的离子电渗输送是感染伤口快速 PACT 治疗的潜在选择。