Abstract The current study was conducted to develop vesicular ethosomal gel (ethogel) systems for upgrading the transdermal delivery of anti-hypertensive carvedilol. Ethosomes composed of Phospholipon 100 H, cholesterol, ethanol, and Transcutol P at different ratios, were prepared by thin-film hydration method with sonication. Carvedilol-loaded ethosomes were characterized by microscopic examinations followed by other in-vitro assessments. Selected ethosomal formulation (E10) was incorporated into different concentrations of gelling agents to prepare the ethogel formulations. Ethogels were subjected to physicochemical characterization, compatibility, and in-vitro drug release studies. Ex-vivo skin permeation and retention studies were performed followed by in-vivo studies in induced hypertensive rats. The smooth ethosomes demonstrated vesicular size of 201.55–398.55 nm, entrapment efficiency of 30.00–90.66% and loading capacity of 7.64–43.04% with zeta potential range of −30.30 to −44.90 mV. The homogeneous ethogels exhibited appropriate results of pH and drug content measurements. Spreadability was observed as a function of viscosity as the latter increased, the former decreased. The ethogel formulation (G2) manifested satisfactory physical appearance, spreadability, viscosity, and in-vitro release. In comparison to pure carvedilol gel, tested formulations (E10 and G2) developed high ex-vivo permeation, steady-state flux and drug retention through skin layers. The in-vivo study of G2 formulation revealed a significant gradual decline (p < 0.01) in the mean arterial pressure of rats at the second hour of experiment (146.11 mmHg) with continuous significant decrease (p < 0.001) after 6 h (98.88 mmHg). In conclusion, ethogels as promising lipid carriers proved their potential to enhance skin permeation with extended anti-hypertensive action of carvedilol.

中文翻译：

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透皮脂质体凝胶纳米载体；一种增强卡维地洛抗高血压作用的有前景的策略

摘要 目前的研究旨在开发用于提高抗高血压卡维地洛透皮给药的囊泡乙醇凝胶（ethogel）系统。由不同比例的 Phospholipon 100 H、胆固醇、乙醇和 Transcutol P 组成的 Ethosomes 通过超声处理的薄膜水化方法制备。载有卡维地洛的 ethosome 的特征在于显微镜检查，然后是其他体外评估。将选定的 ethosomal 制剂 (E10) 掺入不同浓度的胶凝剂中以制备 ethogel 制剂。对 Ethogels 进行物理化学表征、相容性和体外药物释放研究。进行体外皮肤渗透和保留研究，然后在诱导高血压大鼠中进行体内研究。光滑的 ethosomes 显示出 201.55–398.55 nm 的囊泡大小，30.00–90.66% 的包封率和 7.64–43.04% 的负载能力，zeta 电位范围为 -30.30 到 -44.90 mV。均质乙醇凝胶显示出适当的 pH 值和药物含量测量结果。当后者增加时，可观察到作为粘度的函数的铺展性，前者降低。乙醇凝胶制剂 (G2) 表现出令人满意的物理外观、铺展性、粘度和体外释放。与纯卡维地洛凝胶相比，测试配方（E10 和 G2）具有较高的离体渗透性、稳态通量和药物通过皮肤层的保留率。G2 制剂的体内研究显示，在实验的第二个小时，大鼠的平均动脉压显着逐渐下降（p < 0.01）（146. 11 mmHg)，6 小时后持续显着下降 (p < 0.001) (98.88 mmHg)。总之，作为有前途的脂质载体，乙醇凝胶证明了它们具有通过卡维地洛延长的抗高血压作用增强皮肤渗透的潜力。