Preparation and characterization of layer-by-layer hypoglycemic nanoparticles with pH-sensitivity for oral insulin delivery.

New self-assembled layer-by-layer nanoparticles, based on hypoglycemic, mucoadhesive, epithelium-penetrating and pH-sensitive functional materials, have been synthesized. The confirmed hypoglycemic and negatively charged polygalacturonic acid, the well-known cell penetrating and positively charged chitosan, and the negatively charged, pH-sensitive polymer alginate were the components of these nanoparticles. The electrical attraction between the negatively charged PGLA and alginate and the positively charged chitosan motivated the assembly and supported the pH-sensitivity of the nanoparticles. The LBL4 and LBL4-Alg nanoparticles were characterized in vitro and in vivo. The pH-sensitivity of LBL4-Alg nanoparticles was greater, with the turning point near pH = 5. Moreover, according to the pharmacological and pharmacokinetic studies, the significant hypoglycemic effect was observed only 1 h after gavage with LBL4 and LBL4-Alg nanoparticles. Insulin was continually released for at least 6 h. These results show that the new self-assembled LBL4-Alg nanoparticles with pH-sensitivity have great potential for oral insulin delivery.