George M, Abraham T E
Polymer Section, Chemical Science Division, Regional Research Laboratory (CSIR), Trivandrum 19, Trivandrum 695 019, India.
Polymer Section, Chemical Science Division, Regional Research Laboratory (CSIR), Trivandrum 19, Trivandrum 695 019, India.
Int J Pharm. 2007 Apr 20;335(1-2):123-129. doi: 10.1016/j.ijpharm.2006.11.009. Epub 2006 Nov 7.
Design of a pH sensitive alginate-guar gum hydrogel crosslinked with glutaraldehyde was done for the controlled delivery of protein drugs. Alginate is a non-toxic polysaccharide with favorable pH sensitive properties for intestinal delivery of protein drugs. Drug leaching during hydrogel preparation and rapid dissolution of alginate at higher pH are major limitations, as it results in very low entrapment efficiency and burst release of entrapped protein drug, once it enters the intestine. To overcome these limitations, another natural polysaccharide, guargum was included in the alginate matrix along with a cross linking agent to ensure maximum encapsulation efficiency and controlled drug release. The crosslinked alginate-guar gum matrix is novel and the drug loading process used in the study was mild and performed in aqueous environment. The release profiles of a model protein drug (BSA) from test hydrogels were studied under simulated gastric and intestinal media. The beads having an alginate to guar gum percentage combination of 3:1 showed desirable characters like better encapsulation efficiency and bead forming properties in the preliminary studies. The glutaraldehyde concentration giving maximum (100%) encapsulation efficiency and the most appropriate swelling characteristics was found to be 0.5% (w/v). Freeze-dried samples showed swelling ratios most suitable for drug release in simulated intestinal media ( approximately 8.5). Protein release from test hydrogels was minimal at pH 1.2 ( approximately 20%), and it was found to be significantly higher ( approximately 90%) at pH 7.4. Presence of guar gum and glutaraldehyde crosslinking increases entrapment efficiency and prevents the rapid dissolution of alginate in higher pH of the intestine, ensuring a controlled release of the entrapped drug.
设计了一种用戊二醛交联的pH敏感海藻酸钠-瓜尔胶水凝胶,用于蛋白质药物的控释。海藻酸钠是一种无毒多糖,对蛋白质药物的肠道递送具有良好的pH敏感特性。水凝胶制备过程中的药物渗漏以及海藻酸钠在较高pH值下的快速溶解是主要限制因素,因为这会导致包封效率非常低,并且一旦进入肠道,包封的蛋白质药物就会出现突释。为了克服这些限制,在海藻酸钠基质中加入了另一种天然多糖瓜尔胶以及交联剂,以确保最大的包封效率和药物控释。交联的海藻酸钠-瓜尔胶基质是新颖的,并且研究中使用的载药过程温和,是在水性环境中进行的。在模拟胃液和肠液介质中研究了模型蛋白质药物(牛血清白蛋白)从测试水凝胶中的释放曲线。在初步研究中,海藻酸钠与瓜尔胶百分比组合为3:1的珠子表现出理想的特性,如更好的包封效率和成珠性能。发现能给出最大(100%)包封效率和最合适溶胀特性的戊二醛浓度为0.5%(w/v)。冻干样品显示出最适合在模拟肠液介质中药物释放的溶胀率(约为8.5)。测试水凝胶在pH 1.2时蛋白质释放最少(约20%),而在pH 7.4时释放显著更高(约90%)。瓜尔胶的存在和戊二醛交联提高了包封效率,并防止海藻酸钠在肠道较高pH值下快速溶解以确保包封药物的控释。