Department of Chemical Engineering, Texas Tech University, Lubbock, TX 79409, USA.
Department of Chemical Engineering, Texas Tech University, Lubbock, TX 79409, USA.
Int J Pharm. 2018 Dec 1;552(1-2):352-359. doi: 10.1016/j.ijpharm.2018.10.016. Epub 2018 Oct 9.
Oral delivery of proteins and peptides is a challenge due to their degradation in the stomach. To overcome this challenge, ragweed (Ambrosia elatior) pollen grains were engineered to serve as protective microcapsules. A matrix comprising of Eudragit L100-55, an enteric polymer was deposited on the inner surfaces of ragweed pollens to protect the encapsulated protein from gastric degradation and to achieve pH-dependent release in the intestine. The Eudragit L100-55 matrix was formed without use of organic solvents so that solvent-induced damage to protein molecules could be prevented. To demonstrate the concept, bovine serum albumin (BSA) a model protein was used. A matrix of Eudragit L100-55 embedded with BSA was prepared in ragweed pollens by optimizing their respective concentrations for maximizing BSA loading in the matrix. The ability of this optimized formulation to protect BSA in simulated gastric acid fluid was evaluated. Release studies in simulated gastric fluid (pH 1.2) showed minimal BSA release from the ragweed-Eudragit L100-55 formulation. Analysis of BSA retained in the formulation after its exposure to gastric fluid confirmed that the residual BSA had not denatured. Release studies in the simulated intestinal fluid (pH 6.8) showed that ragweed pollen offered additional controlled release mechanism within the first few hours of release by virtue of their solid wall. In conclusion, upon use of a protein-friendly solvent for Eudragit L100-55, proteins could be encapsulated in ragweed pollen without denaturing them, and the resulting formulation exhibited selective release of the proteins at intestinal pH suggesting that the ragweed pollen grain-based formulation could be promising for oral delivery of proteins.
由于蛋白质和肽在胃中降解，因此经口腔递送它们是一个挑战。为了克服这一挑战，野蒿（Ambrosia elatior）花粉粒被设计成保护性微胶囊。由 Eudragit L100-55（一种肠溶聚合物）组成的基质沉积在野蒿花粉的内表面上，以保护包封的蛋白质免受胃降解，并在肠道中实现 pH 依赖性释放。Eudragit L100-55 基质的形成不使用有机溶剂，从而可以防止溶剂对蛋白质分子的损伤。为了证明这一概念，使用了牛血清白蛋白（BSA）作为模型蛋白。通过优化各自的浓度，在野蒿花粉中制备了 Eudragit L100-55 基质包埋 BSA 的基质，以最大限度地提高基质中 BSA 的负载量。评估了这种优化配方在模拟胃液中的保护 BSA 的能力。在模拟胃液（pH 1.2）中的释放研究表明，从野蒿-Eudragit L100-55 制剂中释放出的 BSA 很少。暴露于胃液后保留在制剂中的 BSA 的分析证实，残留的 BSA 没有变性。在模拟肠液（pH 6.8）中的释放研究表明，由于野蒿花粉的实心壁，在最初的几个小时内，野蒿花粉提供了额外的控制释放机制。总之，在使用对蛋白质友好的溶剂制备 Eudragit L100-55 后，蛋白质可以在不使它们变性的情况下包封在野蒿花粉中，并且所得制剂在肠 pH 下表现出蛋白质的选择性释放，这表明基于野蒿花粉的制剂可能是口服递送蛋白质的有前途的方法。
