Chowdhary R K, Ratkay L G, Canaan A J, Waterfield J D, Richter A M, Levy J G
Department of Microbiology, University of British Columbia, Vancouver, Canada.
Biopharm Drug Dispos. 1998 Sep;19(6):395-400. doi: 10.1002/(sici)1099-081x(199809)19:6<395::aid-bdd117>3.0.co;2-9.
Photodynamic therapy (PDT) using the photosensitizer BPD-Verteporfin (liposomal benzoporphyrin derivative-monoacid ring A) has been shown in previous studies to be effective in the amelioration of inflammatory arthritis in both the MRL-lpr mouse and the New Zealand White (NZW) rabbit models, and could potentially offer alleviation of certain inflammation-related symptoms of rheumatoid arthritis. Time and dose dependency of BPD-MA tissue uptake was carried out in the inflamed synovium and other articular and peri-articular tissues following intravenous and intra-articular administration in the NZW rabbit model. As some articular and peri-articular tissues are difficult to extract, this study uses a rapid fluorimetric sampling of tissues following dissolution in Soluene 350. Our results showed that i.v. injected BPD-MA preferentially distributed in the inflamed synovium, and in tissues with a high degree of vascularization. Little or no association was found with avascular tissues such as cartilage and tendons. Clearance from the synovium was rapid, supporting earlier rather than late light treatment. Much higher association of BPD-MA with the synovium was achieved using intra-articular injection, and BPD-MA concentrations were maintained at relatively steady levels for several hours. These observations support the possibility that PDT could offer a safe, highly versatile clinical option for the management of inflamed joints in autoimmune disorders.
在先前的研究中已表明，使用光敏剂维替泊芬（脂质体苯并卟啉衍生物单酸环A，BPD - Verteporfin）的光动力疗法（PDT）在改善MRL - lpr小鼠和新西兰白兔（NZW）模型中的炎性关节炎方面是有效的，并且可能减轻类风湿性关节炎的某些炎症相关症状。在NZW兔模型中，静脉内和关节内给药后，对发炎的滑膜以及其他关节和关节周围组织进行了BPD - MA组织摄取的时间和剂量依赖性研究。由于一些关节和关节周围组织难以提取，本研究采用在Soluene 350中溶解后对组织进行快速荧光采样。我们的结果表明，静脉注射的BPD - MA优先分布在发炎的滑膜以及血管化程度高的组织中。在无血管组织如软骨和肌腱中几乎没有发现关联。滑膜清除迅速，支持早期而非晚期光治疗。通过关节内注射，BPD - MA与滑膜的关联度更高，并且BPD - MA浓度在数小时内保持相对稳定水平。这些观察结果支持了光动力疗法可能为自身免疫性疾病中发炎关节的管理提供一种安全、用途广泛的临床选择的可能性。
