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No abstract

The oral administration of peptidic drugs requires their protection from degradation in the gastric environment and the improvement of their absorption in the intestinal tract. For these requirements, a microsystem based on cross-linked alginate as the carrier of bovine serum albumin (BSA), used as a model protein, was proposed. A spray-drying technique was applied to BSA/sodium alginate solutions to obtain spherical particles having a mean diameter less than 10 microm. The microparticles were hardened using first a solution of calcium chloride and then a solution of chitosan (CS) to obtain stable microsystems. The cross-linking process was carried out at different CS concentrations and pH values of the cross-linking medium. The CS concentration affected the BSA loading in the microparticles prepared at a pH value less than the protein isoelectric point (pI). Moreover, the BSA loading at a pH value less than the pI was higher than that at a pH similar to the pI regardless of the CS concentration. This finding could be attributable to the formation of a BSA/alginate complex. The evaluation of the interaction between BSA and alginate at different pH values by means rheological measurements confirmed this hypothesis. This approach may represent a promising way to devise a microcarrier system with appropriate size for targeting the Peyer's patches, with appropriate immobilization capacity, and suitable for the oral administration of peptidic drugs.

No abstract

Oral administration of peptide and protein drugs requires their protection from the acidic and enzymatic degradation in the gastro-intestinal environment and their targeting to the absorption zone. For this purpose, an alginate microsystem, as a carrier of bovine serum albumin (BSA), as a model protein, was developed using a spray-drying technique. A hardening process with Ca2+ and chitosan (CS) provided a system with resistance to the gastro-intestinal barriers and of appropriate size for targeting to the Peyer's patches. The present work aims to evaluate the effects of the ratio of sodium alginate (Na-A) and BSA as well as the pH of the crosslinking medium on the microsystem properties. Microparticle morphological and dimensional characteristics did not change significantly with the formulation variables. BSA loading at a pH value less than the protein isoelectric point (pI) was higher than that at a pH similar to the pI owing to an electrostatic interaction between the charged protein and the polyanionic alginate. The maximum encapsulation efficiency was obtained at the highest Na-A/BSA ratio. Protein release in a simulated gastro-intestinal fluid was not affected by the preparative variables, but was controlled by the pH-dependent nature of the polymer material. Polyacrylamide gel electrophoresis (PAGE) demonstrated the stability of the protein to both the preparative conditions and the gastro-intestinal pH values.