Crosslinker-free Bovine Serum Albumin-loaded Chitosan/alginate Nanocomplex for pH-responsive Bursting Release of Oral-administered Protein

• Published in: Biotechnology and bioprocess engineering Vol. 27; no. 1; pp. 40 - 50
• Main Authors: Li, Jiaoyang, Jin, Hui, Razzak, Md. Abdur, Kim, Eun Ji, Choi, Shin Sik
• Format: Journal Article
• Language: English
• Published: Seoul The Korean Society for Biotechnology and Bioengineering 01.02.2022; 한국생물공학회
• Subjects: Biotechnology; Chemistry; Chemistry and Materials Science; Industrial and Production Engineering; Research Paper; 생물공학; alginate; low molecular chitosan; bursting release; degree of swelling; complex
• ISSN: 1226-8372; 1976-3816
• DOI: 10.1007/s12257-021-0243-6

The application of protein-based drugs in oral delivery system is limited due to the harsh environment of the gastrointestinal (GI) tract. Herein, a pH-responsive nano-sized complex with chitosan (CH) and alginate (AL) was fabricated without cross-linker as an oral vehicle for bursting release of protein at the target location to enhance the efficacy. Using bovine serum albumin (BSA) as a model cargo protein, four optimized complexation processes (LG1, LG2, LG3, and LG4) were selected by changes of variables (total concentration (TC), the ratio of CH to AL (CH/AL, w/w), and mixing time (MT)) and further modifications using encapsulation efficiency and complex size. Size, ζ-potential, morphology, BSA release, and swelling degrees of the complexes were evaluated under simulated gastrointestinal conditions (pH 2.0 and 7.4). LG1 and LG4 completely retained BSA in complexes at pH 2.0 after 2 h (BSA release percentage is 0%) and exhibited bursting release at pH 7.4 after 1 h (84.03 and 67.59%, respectively). Low absolute ζ-potential value (about 10 mV), large size (over 10000 nm) and polymer morphology demonstrated that the pH-responsive complexes inhibited protein release at pH 2.0 through the molecule-molecule aggregation. Relatively high absolute ζ-potential value (about 45 mV), ideal swelling ability (around 2), and polymer morphology revealed that the complex promoted the release at 7.4 through both micro- and macroscale swelling. Results demonstrate that the CH-BSA-AL complex through LG4 has a potential for administering proteinbased drugs or vaccines orally due to its highest effective dose (78.78 μg/mL).