Preparation and property evaluation of oral colon targeted protein delivery system with sodium alginate and chitosan

Abstract

Oral administration of protein-based biologics faces challenges such as low bioavailability and a short half-life in the gastrointestinal tract. This study focuses on developing a novel encapsulation technique using sodium alginate and chitosan to create nanospheres that efficiently deliver bovine serum albumin, a model protein. Through a combination of single-factor and response surface experiments, optimal preparation conditions were identified, yielding stable nanospheres with high encapsulation rates and small particle sizes. The release of the protein was pH-dependent, with more substantial release under alkaline conditions, resembling the environment of the colon. In vitro safety testing confirmed that the nanospheres had low toxicity and did not induce significant hemolysis or cell death. This approach demonstrates significant potential for enhancing the oral bioavailability of protein-based drugs, overcoming the typical challenges faced by oral drug delivery systems. The developed formulation offers a simple yet effective method for targeted colonic delivery, representing a promising strategy for improving the clinical efficiency of protein biologics.

Keywords: Biosafety; Protein-based biologics; Response surface experiments; SA-BSA-CS; Single-factor experiment.

Fig. 1

Single-factor experiments results: (a) Different mass fractions SA; (b) Different mass fractions CaCl₂; (c) Different stirring times; (d) Different mass fractions CS.

Fig. 2

Response surface plots for the interaction between SA, CaCl₂, stirring time, and CS on EE (%): (a) 3D response surface map of independent variable interactions; (b) Contour plot of independent variable interactions. (Notes: A: SA B: CaCl₂ C: CS D: Stirring time).

Fig. 3

Nanospheres characterization: (a) Prediction and disturbance diagram (A: SA, B: CaCl₂, C: stirring time, D: CS); (b) Size and PDI of SA-BSA-CS; (c) Transmission electron microscope results of SA-BSA-CS; (d) Fourier Infrared Scanning Spectral Composition Analysis of SA-BSA-CS.

Fig. 4

Drug Release from SA-BSA-CS and drug release kinetics fitting (a) Release results of SA-BSA-CS and pure BSA under different pH conditions (b) Validation of pharmacokinetic release model under different pH conditions.

Fig. 5

Biosafety Verification (a) Hemolytic test results of BSA solution and SA-BSA-CS; (b) Cell activity test resultsof BSA solution and SA-BSA-CS; (c) Live and dead cell staining test results of BSA solution and SA-BSA-CS.