Abstract：
This research work is to evaluate spanlastic-loaded raloxifene (RLX) nanogel administration via the transdermal route to avoid its hepatic metabolism and to enhance the bioavailability for better management of osteoporosis. RLX-loaded spanlastic nanogel was prepared and characterized for its viscosity, pH, spreadability, and texture profile. The formulation was applied on the skin surface of the animal for pharmacokinetic evaluation, and later, the efficacy of the formulation was assessed in ovariectomized female Wistar rats. The nanogel was obtained with a viscosity (2552.66 ± 30.61 cP), pH (7.1 ± 0.1), and spreadability (7.1 ± 0.2 cm). The texture properties, cohesiveness, and adhesiveness of the nanogel showed its suitability for transdermal application. Nanogel showed no sign of edema and erythema in the skin irritation test which revealed its safety for transdermal application. The t1/2 obtained for RLX-spanlastic nanogel (37.02 ± 0.59 h) was much higher than that obtained for RLX-oral suspension (14.43 h). The relative bioavailability was found to be 215.96% for RLX-spanlastic nanogel, and the drug and formulation did not show any toxicity in any of the vital organs, as well as no hematological changes occurring in blood samples. In microarchitectural measurement, RLX-spanlastic nanogel exhibited no unambiguous deviations along with improved bone mineral density compared to the RLX suspension treated group. Transdermal administration of RLX-spanlastic nanogel showed significant improvement of drug bioavailability (approx. twice to oral administration) without any toxic effect in the treated rats. Hence, spanlastic nanogel could be a better approach to deliver RLX via transdermal route for the management of osteoporosis.
摘要：
这项研究工作旨在通过透皮途径评估负载有弹性的雷洛昔芬（RLX）纳米凝胶的给药，以避免其肝脏代谢并提高生物利用度，以更好地管理骨质疏松症。制备了RLX负载的弹性纳米凝胶，并对其粘度进行了表征，pH值,铺展性，和纹理轮廓。将该制剂施用于动物的皮肤表面以进行药代动力学评估，后来,在卵巢切除的雌性Wistar大鼠中评估制剂的功效。获得的纳米凝胶的粘度为（2552.66±30.61cP），pH值(7.1±0.1),和铺展性(7.1±0.2cm)。纹理属性，凝聚力,纳米凝胶的粘附性表明其适合经皮应用。纳米凝胶在皮肤刺激试验中没有表现出水肿和红斑的迹象,这表明其对于经皮应用的安全性。RLX-弹性纳米凝胶获得的t1/2（37.02±0.59h）远高于RLX口服悬浮液获得的t1/2（14.43h）。RLX-弹性纳米凝胶的相对生物利用度为215.96%，药物和制剂对任何重要器官都没有任何毒性，以及血液样本中没有发生血液学变化。在微建筑测量中，与RLX悬浮液治疗组相比，RLX-弹性纳米凝胶没有明显的偏差，骨矿物质密度也得到了改善。RLX-弹性纳米凝胶的透皮给药显示药物生物利用度的显着改善（约两次口服给药）在治疗的大鼠中没有任何毒性作用。因此，弹性纳米凝胶可能是通过透皮途径递送RLX治疗骨质疏松症的更好方法。
