Abstract

pH-responsive core-shell structured composite hydrogel beads, composed of a alginate (ALG) core coated with carboxymethyl cellulose (CMC) shell (ALG@CMC), were prepared by using in-situ gel preparation technology as a drug delivery system. An anti-inflammatory drug, indomethacin was loaded into the formed hydrogels as a model drug. The resulting gel samples were characterized by Fourier transforms infrared (FTIR) spectroscopy, thermo-gravimetric (TG) analysis, and scanning electron microscopy (SEM). The mechanical stability of all samples in phosphate buffered solution (PBS, pH 7.4) was approximately measured through oscillation experiments. Swelling and controlled drug release behaviors of ALG@CMC beads compared with ALG were studied in simulating gastric fluid of pH 1.2 or intestinal fluid of pH 7.4 at 37 °C. Oscillation experiments proved that the mechanical stability of ALG@CMC beads could be significantly improved by the CMC shell layer. The swelling and drug release behaviors revealed that the swelling and drug release rate of ALG@CMC beads were obviously slower than that of simple-ALG and both have significant pH responsiveness. The cumulative drug release from ALG, ALG@CMC-1, ALG@CMC-2 and ALG@CMC-3 was about 100%, 67%, 46% and 37% in simulated intestinal fluid of pH 7.4, respectively, while the drug release reached only about 2.0% in simulating gastric fluid of pH 1.2 within 720 min. These developed materials could potentially be employed as a pH-responsive drug delivery device in vivo.

摘要

通过使用原位凝胶制备技术作为药物递送系统，制备了pH响应核壳结构的复合水凝胶珠，由包裹有羧甲基纤维素（CMC）壳（ALG@CMC）的藻酸盐（ALG）核组成。消炎药消炎痛作为模型药物加载到形成的水凝胶中。所得凝胶样品通过傅里叶变换红外 (FTIR) 光谱、热重 (TG) 分析和扫描电子显微镜 (SEM) 进行表征。所有样品在磷酸盐缓冲溶液 (PBS, pH 7.4) 中的机械稳定性通过振荡实验近似测量。与 ALG 相比，ALG@CMC 微珠的溶胀和药物控释行为在 37°C 下模拟 pH 1.2 的胃液或 pH 7.4 的肠液进行了研究。振荡实验证明，CMC壳层可以显着提高ALG@CMC珠的机械稳定性。溶胀和药物释放行为表明，ALG@CMC微珠的溶胀和药物释放速率明显慢于简单的ALG，并且均具有显着的pH响应性。ALG、ALG@CMC-1、ALG@CMC-2 和 ALG@CMC-3 在 pH 7.4 的模拟肠液中的累积药物释放量分别约为 100%、67%、46% 和 37%，而药物在 720 分钟内模拟 pH 1.2 的胃液，释放仅达到约 2.0%。这些开发的材料有可能用作 pH 响应药物输送装置 溶胀和药物释放行为表明，ALG@CMC微球的溶胀和药物释放速率明显慢于简单的ALG，并且均具有显着的pH响应性。ALG、ALG@CMC-1、ALG@CMC-2 和 ALG@CMC-3 在 pH 7.4 的模拟肠液中的累积药物释放量分别约为 100%、67%、46% 和 37%，而药物在 720 分钟内模拟 pH 1.2 的胃液，释放仅达到约 2.0%。这些开发的材料有可能用作 pH 响应药物输送装置 溶胀和药物释放行为表明，ALG@CMC微球的溶胀和药物释放速率明显慢于简单的ALG，并且均具有显着的pH响应性。ALG、ALG@CMC-1、ALG@CMC-2 和 ALG@CMC-3 在 pH 7.4 的模拟肠液中的累积药物释放量分别约为 100%、67%、46% 和 37%，而药物在 720 分钟内模拟 pH 1.2 的胃液，释放仅达到约 2.0%。这些开发的材料有可能用作 pH 响应药物输送装置 而在720分钟内模拟pH 1.2的胃液，药物释放仅达到2.0%左右。这些开发的材料有可能用作 pH 响应药物输送装置 而在720分钟内模拟pH 1.2的胃液，药物释放仅达到2.0%左右。这些开发的材料有可能用作 pH 响应药物输送装置体内。