Department of Pharmaceutics, Gupta College of Technological Sciences, Ashram More, G.T. Road, Asansol, 713301, West Bengal, India(1).
Department of Pharmacy, Indira Gandhi National Tribal University, Amarkantak, Madhya Pradesh, 484887, India.
Colloids Surf B Biointerfaces. 2019 Aug 1;180:263-272. doi: 10.1016/j.colsurfb.2019.04.064. Epub 2019 May 1.
The amphiphilic propyl Karaya gum (KG) with a degree of propyl group substitution of 3.24 was synthesized to design self-assembled nanogels as carriers for bosentan monohydrate, a poorly soluble antihypertensive drug. The drug was physically hosted into the hydrophobic core of the micellar nanogels by solvent evaporation method. TEM images revealed spherical shape and core-shell morphology of the nanogels. Depending upon polymer: drug weight ratio, the drug entrapment efficiency of >85% was attained. The carriers had hydrodynamic diameter in the range of 230-305 nm with narrow size distribution. The zeta potential of -23.0 to -24.9 mV and low critical association concentration (CAC) of 8.32 mg/l provided evidence that the colloidal nanogel system was physically stable. Thermodynamics of the propyl KG system in water favored spontaneous self-assembly of propyl KG. FTIR, thermal and x-ray analyses suggested that the drug was compatible in the hydrophobic confines of the nanogels. The micellar nanogels liberated their contents in simulated gastrointestinal condition in a pH-dependent manner over a period of 10 h. Peppas-Sahlin modeling of in vitro drug release data suggested that the polymer relaxation/swelling mechanism dominated the drug release process. Pre-clinical testing of the mucoadhesive nanogel formulations exhibited that the system could monitor the anti-hypertensive activity for a prolonged period. Overall, this propyl KG micellar nanogel system had a great potential and splendid outlook to serve as novel oral controlled release carriers for poorly soluble drugs with outstanding pharmacodynamics.
合成了具有 3.24 度丙基取代度的两亲性丙基卡拉胶 (KG)，旨在设计自组装纳米胶作为水合波生坦的载体，水合波生坦是一种难溶性抗高血压药物。通过溶剂蒸发法将药物物理包封到胶束纳米胶的疏水性内核中。TEM 图像显示了纳米胶的球形形状和核壳形态。根据聚合物与药物的重量比，药物包封效率超过 85%。载体的水动力直径在 230-305nm 范围内，具有较窄的粒径分布。Zeta 电位为-23.0 至-24.9mV，低临界聚集浓度（CAC）为 8.32mg/L，证明胶体纳米胶系统是物理稳定的。KG 系统在水中的热力学有利于 KG 的自发自组装。FTIR、热分析和 X 射线分析表明，药物在纳米胶的疏水环境中是相容的。在模拟胃肠道条件下，纳米胶在 pH 依赖性条件下在 10h 内释放其内容物。体外药物释放数据的 Peppas-Sahlin 模型表明，聚合物弛豫/溶胀机制主导了药物释放过程。亲脂性纳米胶制剂的临床前测试表明，该系统可以长时间监测抗高血压活性。总的来说，这种丙基 KG 胶束纳米胶系统具有很大的潜力和良好的前景，可作为具有出色药效学的难溶性药物的新型口服控释载体。
