Karasulu H Yeşim, Oruç Nevin, Üstündağ-Okur Neslihan, İlem Özdemir Derya, Ay Şenyiğit Zeynep, Barbet Yılmaz Funda, Aşıkoğlu Makbule, Özkılıç Hayal, Akçiçek Eren, Güneri Tamer, Özütemiz Ömer
Department of Pharmaceutical Technology, Faculty of Pharmacy .
J Drug Target. 2015;23(6):525-37. doi: 10.3109/1061186X.2015.1015537. Epub 2015 Mar 4.
The aim of this study was to develop aprotinin-loaded microemulsion (MA) for intravenous administration and evaluate the biodistribution and therapeutic potential of developed formulation in acute pancreatitis models in rats. Phase diagrams were constructed to identify microemulsion region and the optimal microemulsion was evaluated for physicochemical properties and treatment effect in rats, and comparisons made with the solution of aprotinin (SA). To evaluate the biodistribution of the drug by gamma scintigraphy aprotinin was radiolabeled with (99m)Tc radionuclide. Mild and severe acute pancreatitis was induced in rats by subcutaneous injections of cerulein and introductal infusion of 3% sodium taurocholate into the bile-pancreatic duct, respectively. In addition, serum amylase and pancreatic tissue myeloperoxidase activities were measured to evaluate the pancreatic damage. According to gamma scintigraphy and biodistribution studies, accumulation times and distribution of (99m)Tc-MA and SA were different. While MA was highly uptake by reticuloendothelial system, SA was mostly excreted by kidneys and bladder. Compared with the mild acute pancreatitis group, treatment with MA significantly decreased the serum amylase activity and pancreas myeloperoxidase activity. Furthermore, the protease inhibitor molecule aprotinin has therapeutic potential in acute pancreatitis. Finally, MA may be suggested as a promising alternative for treatment of acute pancreatitis.
本研究的目的是开发一种用于静脉给药的载抑肽酶微乳剂（MA），并评估所开发制剂在大鼠急性胰腺炎模型中的生物分布和治疗潜力。构建相图以确定微乳区域，并对最佳微乳剂的理化性质和对大鼠的治疗效果进行评估，并与抑肽酶溶液（SA）进行比较。为了通过γ闪烁显像评估药物的生物分布，用（99m）Tc放射性核素对抑肽酶进行放射性标记。分别通过皮下注射雨蛙肽和向胆胰管内注入3%牛磺胆酸钠诱导大鼠发生轻度和重度急性胰腺炎。此外，测量血清淀粉酶和胰腺组织髓过氧化物酶活性以评估胰腺损伤。根据γ闪烁显像和生物分布研究，（99m）Tc-MA和SA的蓄积时间和分布不同。MA被网状内皮系统高度摄取，而SA主要通过肾脏和膀胱排泄。与轻度急性胰腺炎组相比，MA治疗显著降低了血清淀粉酶活性和胰腺髓过氧化物酶活性。此外，蛋白酶抑制剂分子抑肽酶在急性胰腺炎中具有治疗潜力。最后，MA可能被认为是治疗急性胰腺炎的一种有前景的替代方法。
