Preparation And Applications Of PH-sensitive Calcium Alginate Porous Hydrogel Microspheres

The oral administration of protein drugs is easily affected by GI pH value, enzyme system, and first-pass effect, as a result of fraction of bioavailability. Protein drugs are commonly given by injection in clinic. Using the sensitive hydrogels to encapsulate protein drugs can avoid these situations. However, the slow response rate of sensitive hydrogels still exists. When hydrogels reach their sensitive environment, they can't release protein drugs immediately. Hence, how to improve response rate of sensitive hydrogels is the key problem to be solved. This paper argued that sodium alginate was used to prepare a kind of quick-response, pH-sensitive, calcium alginate porous gel microsphere, and bovine serum albumin was chosen as a protein drug's model for embedding. Furthermore, releasing rate of gel microspheres with BSA was investigated in the simulated gastric juice and intestinal liquid.Better preparation conditions were obtained by orthogonal experiment:2wt% sodium alginate,3wt% calcium chloride, gelling temperature of 60℃and heat preservation time for 40min. The swelling ratio of gel microspheres was 21.8 after swelling in a pH 7.4 buffer solution for 30min.Several kinds of pore formers were added into the gel microspheres to investigate their effects on swelling response rate. The gel microspheres achieved the biggest swelling ratio in 30min in the pH 7.4 buffer solution without the existence of pore former. While after a proper addition of PEG200, PEG400 or NaCl, the swelling response rate was increased significantly. The time to swell to the biggest swelling ratio was shortened to 10min and 12min respectively with 5% volume content of PEG200 or PEG400, while it was 20min with 0.5wt% NaCl. Meanwhile, the influence of mixed pore former was investigated. The results demonstrated that it had no positive impacts on improving swelling response rate.The gel microspheres loading BSA were prepared under the preferred preparation conditions. The results revealed that both embedding ratio and drug-loading rate of BSA were at alow level. The average embedding ratio was only 10%, and drug-loading rate was mostly less than 5%. The embedding ratio of BSA increased to 85% after the pH value of calcium chloride solution was set to 3.52. However, when pH value was too low, it would easily cause the protonation of calcium alginate and acid hydrolysis of BSA. Therefore, the pH value of calcium chloride solution was chosen at 4. Under this pH value, the embedding ratio was 60%, and drug-loading rate was 11%.The gel microspheres embedding BSA were placed into the simulated gastric juice and intestinal liquid. The BSA release ratio for cumulative 4h (gastric emptying time) was lower than 21% in the simulated gastric juice, and reached 90% around in the simulated intestinal liquid for cumulative 48h, whether gel microspheres were added pore former or not. The ratio for cumulative 40min in the intestinal liquid with pore former was 70%, while it was only 30% without pore former within the same time.