Pegaz Bernadette, Debefve Elodie, Ballini Jean-Pierre, Konan-Kouakou Yvette Niamien, van den Bergh Hubert
Ecole Polytechnique Federale de Lausanne, Faculté des Sciences de base, Laboratory of Photomedicine, Station 6, CH-1015 Lausanne, Switzerland.
J Photochem Photobiol B. 2006 Dec 1;85(3):216-22. doi: 10.1016/j.jphotobiol.2006.07.008. Epub 2006 Sep 18.
Particle size should be optimized to achieve targeted and extended drug delivery to the affected tissues. We describe here the effects of the mean particle size on the pharmacokinetics and photothrombic activity of meso-tetra(carboxyphenyl)porphyrin (TCPP), which is encapsulated into biodegradable nanoparticles based on poly(d,l-lactic acid). Four batches of nanoparticles with different mean sizes ranging from 121 to 343 nm, were prepared using the emulsification-diffusion technique. The extravasations of each TCPP-loaded nanoparticle formulation from blood vessels were measured, as well as the extent of photochemically induced vascular occlusion. These preclinical tests were carried out in the chorioallantoic membrane (CAM) of the chicken's embryo. Fluorescence microscopy showed that both the effective leakage of TCPP from the CAM blood vessels and its photothrombic efficiency were dependent on the size of the nanoparticle drug carrier. Indeed, the TCPP fluorescence contrast between the blood vessels and the surrounding tissue increased at the applied conditions, when the particle size decreased. This suggests that large nanoparticles are more rapidly eliminated from the bloodstream. In addition, after injection of a drug dose of 1mg/kg body weight and a drug-light application interval of 1 min, irradiation with a fluence of 10J/cm(2) showed that the extent of vascular damage gradually decreased when the particle size increased. The highest photothrombic efficiency was observed when using the TCPP-loaded nanoparticles batch with a mean diameter of 121 nm. Thus, in this range of applied conditions, for the treatment of for instance a disease like choroidal neovascularization (CNV) associated with age-related macular degeneration (AMD), these experiments suggest that the smallest nanoparticles may be considered as the optimal formulation since they exhibited the greatest extent of vascular thrombosis as well as the lowest extravasation.
应优化粒径，以实现药物向受影响组织的靶向和延长递送。我们在此描述了平均粒径对中-四（羧基苯基）卟啉（TCPP）的药代动力学和光血栓形成活性的影响，该卟啉被封装在基于聚（d，l-乳酸）的可生物降解纳米颗粒中。使用乳化-扩散技术制备了四批平均粒径在121至343nm之间的不同纳米颗粒。测量了每种负载TCPP的纳米颗粒制剂从血管中的渗出情况，以及光化学诱导的血管闭塞程度。这些临床前试验在鸡胚的绒毛尿囊膜（CAM）中进行。荧光显微镜显示，TCPP从CAM血管中的有效渗漏及其光血栓形成效率均取决于纳米颗粒药物载体的大小。实际上，在所应用的条件下，当粒径减小时，血管与周围组织之间的TCPP荧光对比度增加。这表明大的纳米颗粒从血流中清除得更快。此外，在注射1mg/kg体重的药物剂量且药物-光照应用间隔为1分钟后，以10J/cm(2)的能量密度照射显示，当粒径增加时，血管损伤程度逐渐降低。当使用平均直径为121nm的负载TCPP的纳米颗粒批次时，观察到最高的光血栓形成效率。因此，在该应用条件范围内，例如对于治疗与年龄相关性黄斑变性（AMD）相关的脉络膜新生血管（CNV）等疾病，这些实验表明最小的纳米颗粒可被视为最佳制剂，因为它们表现出最大程度的血管血栓形成以及最低的渗出。
