Background: Extracorporeal photopheresis (ECP) is an effective immunomodulatory therapy for various diseases. Autologous leukocytes are collected, photoactivated with a photosensitizer (8-methoxypsoralen, 8-MOP) and UVA light, and subsequently reinfused back to the patient. Leukapheresis and UVA irradiation systems can be integrated into one device (inline) or handled by two separate devices (offline). ECP works via intercalation of 8-MOP into DNA helices and UVA-based interactions to inhibit DNA replication. 8-MOP is known to adhere to plastic materials, which might reduce its availability for intercalation. In the present study we examined the bioavailability of 8-MOP when different plastic materials and solvents are used as matrices. Methods: Varying amounts of shredded ethylene vinyl acetate (EVA) and polyvinylchloride (PVC) from the MacoGenic irradiation bag (EVA1), UVA PIT irradiation bag (EVA2), UVA PIT recirculation bag (PVC A) and UVA PIT tubing (PVC B) by MacoPharma and PIT Medical Systems, respectively, were incubated with 200 ng mL⁻¹ 8-MOP dissolved in diisopropyl ether (DIPE) plus toluene 90/10 vol%, deionized water or plasma. After 2 h 8-MOP concentrations were determined by GC-MS. Results: After incubation, 8-MOP concentrations varied depending on the amount and type of plastic (PVC > EVA) and solvent (water > plasma > DIPE/toluene). Absorption to 200 mg EVA1 or EVA2 resulted in 8-MOP concentrations of 57% or 32% in water, 91% or 80% in plasma, and 93% or 92% in DIPE/toluene, while 200 mg PVC A and PVC B yielded recovery rates of 26% and 10% in water, 76% and 75% in plasma, and 55% and 30% in DIPE/toluene, respectively. Remaining 8-MOP differed significantly between container materials (EVA vs. PVC; p < 0.022) but not manufacturers (MacoPharma vs. PIT Medical Systems). Conclusion: Absorption loss of 8-MOP depends on the type of plastic and solvent and is more pronounced with water than with plasma. As the DNA binding effect of 8-MOP is dose-dependent, ECP starting doses should be adjusted to ensure that a sufficient concentration of free bioavailable 8-MOP is present during UV irradiation.

中文翻译：

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体外光采中依赖于基质的8-甲氧基补骨脂素吸收。

背景：体外光胆疗法（ECP）是一种有效的针对各种疾病的免疫调节疗法。收集自体白细胞，用光敏剂（8-甲氧基补骨脂素，8-MOP）和UVA光光活化，然后重新注入患者体内。白细胞去除术和UVA照射系统可以集成到一个设备中（在线），也可以由两个单独的设备处理（离线）。ECP通过将8-MOP插入DNA螺旋中以及基于UVA的相互作用来抑制DNA复制。已知8-MOP会粘附到塑料材料上，这可能会降低其插入的可用性。在本研究中，我们检查了当使用不同的塑料材料和溶剂作为基质时8-MOP的生物利用度。方法：通过以下方式，从MacoGenic辐照袋（EVA1），UVA PIT辐照袋（EVA2），UVA PIT再循环袋（PVC A）和UVA PIT管（PVC B）中取出不同数量的切碎的乙烯乙酸乙烯酯（EVA）和聚氯乙烯（PVC）将MacoPharma和PIT Medical Systems分别与溶解在二异丙醚（DIPE）和90/10体积％甲苯，去离子水或血浆中的200 ng mL ^-1 8-MOP孵育。2小时后，通过GC-MS测定8-MOP浓度。结果：孵育后，8-MOP的浓度根据塑料的种类和类型（PVC> EVA）和溶剂（水>血浆> DIPE /甲苯）的不同而不同。吸收至200 mg EVA1或EVA2后，水中的8-MOP浓度分别为57％或32％，血浆91％或80％，DIPE /甲苯93％或92％，而产生200 mg PVC A和PVC B水中的回收率分别为26％和10％，血浆中的回收率分别为76％和75％，DIPE /甲苯的回收率分别为55％和30％。其余的8-MOP在容器材料之间（EVA与PVC；p <0.022）之间存在显着差异，但在制造商之间没有差异（MacoPharma与PIT Medical Systems之间）。结论：8-MOP的吸收损失取决于塑料和溶剂的类型，与水相比，与血浆相比，吸收损失更为明显。由于8-MOP的DNA结合效应是剂量依赖性的，因此应调整ECP起始剂量，以确保在紫外线照射期间存在足够浓度的游离生物可利用的8-MOP。