Kitazawa H, Sato H, Adachi I, Masuko Y, Horikoshi I
Department of Hospital Pharmacy, Toyama Medical and Pharmaceutical University, Japan.
Biol Pharm Bull. 1997 Mar;20(3):278-81. doi: 10.1248/bpb.20.278.
This study was designed to assess a local drug delivery system of an anticancer agent, doxorubicin (DOX), using fibrin glue (Beriplast P) as a drug carrier. In vitro release of DOX from the fibrin glue was examined by a dialysis method in the presence and absence of sodium alginate. The in vitro mean dissolution times of DOX with solution, fibrin glue, and fibrin glue containing sodium alginate were 3.7 h, 8.7 h, and 81 h, respectively, indicating a sustained release of DOX from fibrin glue, especially in the presence of sodium alginate. Fibrin glue containing 6 mg of DOX and 2.5 mg of sodium alginate was applied on the surface of an AH60C tumor at the back of rats. DOX concentrations in the tumor extracellular fluid were monitored by a microdialysis method. Local application of DOX using fibrin glue containing sodium alginate to the tumor resulted in extremely higher concentrations in the tumor extracellular fluid than those in plasma (AUC ratio > 800), indicating an advantage of the site-specific delivery of DOX using fibrin glue with sodium alginate. The tumor volumes were inversely correlated with tumor extracellular fluid-to-plasma AUC ratios (r = 0.882), suggesting the relevance of tumor size in the drug efflux from tumor to blood. In conclusion, the site-specific delivery of DOX using fibrin glue with sodium alginate to the tumor was demonstrated to be advantageous with regard to the extent and duration of drug concentrations in the tumor extracellular fluid, as assessed by a microdialysis technique.
本研究旨在评估一种以纤维蛋白胶（百瑞普P）为药物载体的抗癌药物阿霉素（DOX）的局部给药系统。采用透析法在有无海藻酸钠存在的情况下检测DOX从纤维蛋白胶中的体外释放情况。DOX在溶液、纤维蛋白胶和含海藻酸钠的纤维蛋白胶中的体外平均溶解时间分别为3.7小时、8.7小时和81小时，表明DOX从纤维蛋白胶中持续释放，尤其是在有海藻酸钠存在的情况下。将含6mg DOX和2.5mg海藻酸钠的纤维蛋白胶涂抹于大鼠背部AH60C肿瘤表面。采用微透析法监测肿瘤细胞外液中的DOX浓度。将含海藻酸钠的纤维蛋白胶局部应用于肿瘤，导致肿瘤细胞外液中的浓度比血浆中的浓度极高（AUC比值>800），表明使用含海藻酸钠的纤维蛋白胶进行DOX的位点特异性给药具有优势。肿瘤体积与肿瘤细胞外液与血浆的AUC比值呈负相关（r = 0.882），提示肿瘤大小与药物从肿瘤向血液的外排有关。总之，通过微透析技术评估，使用含海藻酸钠的纤维蛋白胶将DOX位点特异性递送至肿瘤在肿瘤细胞外液中的药物浓度范围和持续时间方面具有优势。
