Ramkanth S, Anitha P, Gayathri R, Mohan S, Babu Dinesh
Department of Pharmaceutics, Karpagam College of Pharmacy, Coimbatore, 641032, Tamilnadu, India.
Department of Pharmaceutics, Annamacharya College of Pharmacy, Rajampet, 516126, Andhra Pradesh, India.
Eur J Pharm Sci. 2021 Jul 1;162:105811. doi: 10.1016/j.ejps.2021.105811. Epub 2021 Mar 20.
Hypertension, a form of cardiovascular diseases, is considered a major risk factor associated with deaths in type 2 diabetes patients. The current medication systems for treating such chronic coexisting diseases are limited and challenging due to the difficulties in overcoming the side effects from complex therapeutic and treatment regimen. The objective of the present study is to design and optimize pioglitazone (PIO) and eprosartan mesylate (EM)-loaded nano-transferosomes (NTs) using Design-Expert software, aiming its transdermal delivery as a novel combination therapy for concomitant treatment of hypertensive diabetic patients. The developed formulations were characterized for various parameters, including in-vitro skin permeation, skin irritation, in-vivo antidiabetic, and antihypertensive activities. NTs were prepared using PIO and EM as the two model drugs and optimized using Box-Behnken design by considering phospholipid (X1), surfactant (X2), ratio of solvents (X3), and sonication time (X4), as independent variables, each at three levels. Entrapment efficiency (Y1 and Y2) and flux (Y3 and Y4) of PIO and EM, respectively, were selected as dependent variables. Among all the prepared formulations, one optimized formulation was chosen by the point prediction method and evaluated for drug-polymer compatibility, particle size, and surface charge analysis, followed by skin permeation and pharmacodynamic studies. The optimized nano-transferosomal gel (ONTF) showed all responses which confirm with the values predicted by the design. Pharmacodynamic studies showed improved and prolonged management of diabetes and hypertension in Wistar rats after the ONTF was applied, compared to oral and drug-loaded NT formulations. Results of the current study suggest that the development of such combinational delivery system can result in a rational therapeutic regimen for effective treatment of concomitant disease conditions of diabetic hypertensive patients.
高血压是心血管疾病的一种形式，被认为是2型糖尿病患者死亡的主要危险因素。由于难以克服复杂治疗方案带来的副作用，目前用于治疗此类慢性并存疾病的药物系统有限且具有挑战性。本研究的目的是使用Design-Expert软件设计并优化载有吡格列酮（PIO）和甲磺酸依普罗沙坦（EM）的纳米传递体（NTs），旨在将其经皮给药作为一种新型联合疗法用于同时治疗高血压糖尿病患者。对所开发的制剂进行了各种参数表征，包括体外皮肤渗透、皮肤刺激性、体内抗糖尿病和抗高血压活性。以PIO和EM作为两种模型药物制备NTs，并通过Box-Behnken设计进行优化，将磷脂（X1）、表面活性剂（X2）、溶剂比例（X3）和超声处理时间（X4）作为自变量，各有三个水平。分别选择PIO和EM的包封率（Y1和Y2）以及通量（Y3和Y4）作为因变量。在所有制备的制剂中，通过点预测法选择一种优化制剂，并对其进行药物-聚合物相容性、粒径和表面电荷分析，随后进行皮肤渗透和药效学研究。优化后的纳米传递体凝胶（ONTF）显示出所有响应，与设计预测值相符。药效学研究表明，与口服和载药NTs制剂相比，应用ONTF后Wistar大鼠的糖尿病和高血压得到了改善且管理时间延长。本研究结果表明，开发这种联合递送系统可为有效治疗糖尿病高血压患者的并存疾病状况带来合理的治疗方案。
