Garripelli Vivek Kumar, Namgung Ran, Kim Won Jong, Jo Seongbong
a Department of Pharmaceutics, School of Pharmacy , The University of Mississippi , University , MS-38677 , USA.
J Biomater Sci Polym Ed. 2012;23(12):1505-19. doi: 10.1163/092050611X584414. Epub 2012 May 8.
A Pluronic(®)-based pH-sensitive multiblock co-polymer thermogel has been proposed for sustained release of therapeutic agents. Hydrophobic small-molecule drugs (paclitaxel and camptothecin) and model hy-drophilic macromolecules (fluorescein-labeled dextrans of molecular mass 10, 20, 40, 150 and 250 kDa) were successfully loaded into and released from the thermogels. Drug-loaded polymer solutions were characterized for gelation behavior and micelle size. Drug loading increased the size of the multiblock co-polymer micelles from 20 to 100 nm. The co-polymer improved paclitaxel and camptothecin loading in an aqueous solution by 6900- and 1050-fold, respectively, compared to their solubility in water. The ther-mogels released loaded drugs in a pH-dependent fashion, regardless of their properties. At pH 5.0 and 6.5, paclitaxel and camptothecin completely released in 4 and 15 days, respectively, by a combined mechanism of diffusion and erosion. At neutral pH, diffusion predominated gel erosion to sustain the drug release up to 40 days. Fluorescein-labeled dextran release from the thermogels showed a similar pH-dependent trend as the hydrophobic small molecule drugs. However, dextran release at neutral pH was entirely dependent on the molecular mass of the dextran. Low-molecular-mass (10 and 20 kDa) dextrans were completely released in 12 and 21 days, respectively, while high-molecular-mass (⩾40 kDa) dextrans being continuously released over 36 days, indicating that the threshold of molecular weight necessary for sustained release of a hydrophilic macromolecule from this thermogel (e.g., enzymes, monoclonal antibodies and immunotoxins) is 40 kDa. Taken together, the MBCP thermogel showed potential as a controlled drug-delivery system that showed sustained release of both hydrophilic and lipophilic molecules.
一种基于普朗尼克（®）的pH敏感多嵌段共聚物热凝胶已被提出用于治疗剂的持续释放。疏水性小分子药物（紫杉醇和喜树碱）以及模型亲水性大分子（分子量为10、20、40、150和250 kDa的荧光素标记葡聚糖）成功地载入热凝胶并从其中释放出来。对载药聚合物溶液的凝胶化行为和胶束尺寸进行了表征。载药使多嵌段共聚物胶束的尺寸从20纳米增加到100纳米。与它们在水中的溶解度相比，该共聚物分别使紫杉醇和喜树碱在水溶液中的载药量提高了6900倍和1050倍。热凝胶以pH依赖的方式释放所载药物，而与药物性质无关。在pH 5.0和6.5时，紫杉醇和喜树碱分别在4天和15天内通过扩散和侵蚀的联合机制完全释放。在中性pH下，扩散主导凝胶侵蚀以维持药物释放长达40天。荧光素标记葡聚糖从热凝胶中的释放显示出与疏水性小分子药物相似的pH依赖趋势。然而，中性pH下葡聚糖的释放完全取决于葡聚糖的分子量。低分子量（10和20 kDa）葡聚糖分别在12天和21天内完全释放，而高分子量（⩾40 kDa）葡聚糖在36天内持续释放，这表明从这种热凝胶中持续释放亲水性大分子（如酶、单克隆抗体和免疫毒素）所需的分子量阈值为40 kDa。综上所述，MBCP热凝胶显示出作为一种控释药物递送系统的潜力，该系统能持续释放亲水性和疏水性分子。
