Development of Microspheres Based on Thiol-Modified Sodium Alginate for Intestinal-Targeted Drug Delivery

Bioactive peptide drugs are mostly delivered by parenteral administration, which brings great pain and risks to patients. Oral administration is an acceptable alternative form. However, peptide drugs are extremely sensitive to the strong acidic environment in the stomach after oral administration. They would be degraded by pepsin and trypsin in the gastrointestinal tract. Herein, we present microspheres for intestinal-targeted peptides drug delivery through oral administration. Sodium alginate was reacted with l-cysteine to bring it into thiol groups. Then sodium alginate-l-cysteine conjugates were mixed with native sodium alginate and emulsified by an improved method. Ca²⁺ was used to fix the emulsion to get the microspheres. Bovine serum albumin was used as the simulating drug to assess the feasibility of microspheres as intestinal delivery carriers. The results showed that the microspheres exhibited spherical properties and narrow size distribution. The drug-loading capacity of microspheres was not compromised after thiol-modification. It is interesting that the microspheres can maintain structural integrity and hold drugs in the strong acidic environment in the stomach. Conversely, the microspheres presented sustained intestinal-targeted drugs release ability as expected. Moreover, thiol-modification further improved the adherence ability of microspheres on the inner walls of the small intestine, which is good for enhancing drug permeability. In sum, the microspheres based on thiol-modified sodium alginate have promising applications as intestinal-targeted macromolecular drug carriers.