Abstract: The enhanced stability of peptide-loaded γ-cyclodextrin metal-organic frameworks (γ-CD-MOFs) modified by cellulose templates and soybean lecithin was studied to provide theoretical guidance for developing gastric juice-stable MOF-based intestinal drug delivery systems. γ-CD-MOFs were prepared through in-situ growth on cellulose surfaces. The effects of cellulose templates of two different sizes on the structure, specific surface area, and peptide-loading capacity of γ-CD-MOFs were investigated. The aqueous stability and sustained release of the peptide-loaded γ-CD-MOFs encapsulated by soybean lecithin were analyzed. The results revealed that γ-CD crystallized on the surface of soybean cellulose microfibrils, forming cubic metal-organic framework particles. The presence of soybean cellulose microfibrils influenced the molecular rearrangement during γ-CD crystallization, thereby affecting the positions of the MOF diffraction and hydroxyl stretching vibration peaks. The surface area of soybean cellulose microfibrils mediated γ-CD-MOFs and their adsorption capacity for the oligopeptide VS-6 reached 422.98 m2/g and 80.25%, 59.77% and 35.81% higher than those of γ-CD-MOFs, respectively. Fluorescent labeling spectroscopic analysis confirmed that soybean lecithin at an appropriate concentration (2.5 mg/mL) coated the surface of γ-CD-MOFs, thus inhibiting K–O bond cleavage in the aqueous phase and reducing the hydrophilicity of γ-CD-MOFs (water contact angle increased to 42.19°). This in turn resulted in slower release and less activity loss of peptide-loaded γ-CD-MOFs in simulated gastric juice.

Key words: cyclodextrin; metal-organic frameworks; cellulose microfibril; lecithin; encapsulation; in-situ growth