Vargas Angelica, Pegaz Bernadette, Debefve Elodie, Konan-Kouakou Yvette, Lange Norbert, Ballini Jean-Pierre, van den Bergh Hubert, Gurny Robert, Delie Florence
Department of Pharmaceutics and Biopharmaceutics, School of Pharmacy, University of Geneva, 30, quai E. Ansermet, CH-1211 Geneva 4, Switzerland.
Int J Pharm. 2004 Nov 22;286(1-2):131-45. doi: 10.1016/j.ijpharm.2004.07.029.
Hydrophobic porphyrins are potentially interesting molecules for the photodynamic therapy (PDT) of solid cancers or ocular vascularization diseases. Their pharmaceutical development is, however, hampered by their lipophilicity, which renders formulation difficult especially when intravenous administration is needed. Encapsulation of a lipophilic derivative of porphyrin, the meso-tetra(p-hydroxyphenyl)porphyrin (p-THPP), into polymeric biodegradable poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles proved to enhance its photodynamic activity against mammary tumour cells when compared to free drug. In order to further investigate these carriers, the efficacy of the encapsulated drug was assessed on the chick embryo chorioallantoic membrane (CAM) model. First, we identified a suitable solvent for the drug in terms of p-THPP solubility and tolerability by chick embryos. This solution was used as a reference. Then, the fluorescence pharmacokinetics and the photodynamic effects of the porphyrin on CAM vessels were evaluated after intravenous administration of either a p-THPP solution (free drug) or the drug loaded into nanoparticles. The results showed that: (i) the drug remained longer in the vascular compartment when incorporated into nanoparticles and (ii) vascular effects of p-THPP after light irradiation were enhanced with nanoparticle carriers. These results are discussed taking into account the extravasation of intravascular circulating photosensitizers and its influence on PDT performance.
疏水性卟啉对于实体癌或眼部血管生成疾病的光动力疗法（PDT）而言是潜在的有趣分子。然而，它们的药物研发受到其亲脂性的阻碍，这使得制剂过程变得困难，尤其是在需要静脉给药时。将卟啉的亲脂性衍生物——中位 - 四（对羟基苯基）卟啉（p - THPP）封装到可生物降解的聚（D，L - 丙交酯 - 共 - 乙交酯）（PLGA）纳米颗粒中，与游离药物相比，已证明能增强其对乳腺肿瘤细胞的光动力活性。为了进一步研究这些载体，在鸡胚绒毛尿囊膜（CAM）模型上评估了封装药物的疗效。首先，就p - THPP在鸡胚中的溶解度和耐受性而言，我们确定了一种适合该药物的溶剂。该溶液用作对照。然后，在静脉注射p - THPP溶液（游离药物）或负载药物的纳米颗粒后，评估了卟啉在CAM血管上的荧光药代动力学和光动力效应。结果表明：（i）当药物被封装到纳米颗粒中时，其在血管腔室中停留的时间更长；（ii）纳米颗粒载体增强了光照后p - THPP的血管效应。结合血管内循环光敏剂的外渗及其对PDT性能的影响对这些结果进行了讨论。
