Reddy Thimma T, Lavenant Laurence, Lefebvre Jacques, Renard Denis
Institut National de la Recherche Agronomique, Centre de Nantes, BP 71627-44316 Nantes Cedex 03, France.
Biomacromolecules. 2006 Jan;7(1):323-30. doi: 10.1021/bm050688d.
Physically cross-linked beta-lactoglobulin (BLG) protein gels containing theophylline and sulfamethoxazole low molecular weight drugs were prepared in 50% ethanol solution at pH 8 and two protein concentrations (6 and 7% (w/v)). Swelling behavior of cylindrical gels showed that, irrespective of the hydrated or dehydrated state of the gel, the rate of swelling was the highest in water. When the gels were exposed to water, they first showed a swelling phase in which their weight increased 3 and 30 times for hydrated and dehydrated gels, respectively, due to absorption of water, followed by a dissolution phase. The absorption of solvent was however considerably reduced when the gels were exposed to aqueous buffer solutions. The release behavior of both theophylline and sulfamethoxazole drugs from BLG gels was achieved in a time window ranging from 6 to 24 h. The drug release depended mainly on the solubility of the drugs and the physical state of the gel (hydrated or dry form). Analysis of drug release profiles using the model of Peppas showed that diffusion through hydrated gels was governed by a Fickian process whereas diffusion through dehydrated gels was governed partly by the swelling capacities of the gel but also by the structural rearrangements inside the network occurring during dehydration step. By a judicious selection of protein concentration, hydrated or dehydrated gel state, drug release may be modulated to be engineered suitable for pharmaceutical as well as cosmetics and food applications.
在pH值为8的50%乙醇溶液中,以两种蛋白质浓度(6%和7%(w/v))制备了含有茶碱和磺胺甲恶唑低分子量药物的物理交联β-乳球蛋白(BLG)蛋白凝胶。圆柱形凝胶的溶胀行为表明,无论凝胶处于水合状态还是脱水状态,在水中的溶胀速率都是最高的。当凝胶接触水时,它们首先呈现溶胀阶段,由于吸水,水合凝胶和脱水凝胶的重量分别增加3倍和30倍,随后是溶解阶段。然而,当凝胶接触缓冲水溶液时,溶剂的吸收会显著减少。茶碱和磺胺甲恶唑药物从BLG凝胶中的释放行为在6至24小时的时间窗口内实现。药物释放主要取决于药物的溶解度和凝胶的物理状态(水合或干燥形式)。使用Peppas模型对药物释放曲线进行分析表明,通过水合凝胶的扩散受菲克过程控制,而通过脱水凝胶的扩散部分受凝胶的溶胀能力控制,也受脱水步骤中网络内部发生的结构重排控制。通过明智地选择蛋白质浓度、水合或脱水凝胶状态,可以调节药物释放,以设计出适用于制药以及化妆品和食品应用的产品。