Effect of chitosan nanocarriers on the interaction between cimetidine and bovine serum albumin and its regulation of protein conformation.

Investigating chitosan nanoparticles (CS NPs) as drug carriers for improving cimetidine delivery (CMT), regulating drug-protein interactions and maintaining protein function, this study considers adsorption mechanisms, molecular interactions, protein conformation and biological function. Characterisation using methods, such as scanning electron microscopy and dynamic light scattering, indicates that CMT is loaded onto CS NPs non-covalently through hydrogen bonding, forming stable complexes with porous structures. The average particle size of the complex is 415.7 nm, and the zeta potential is +31.52 mV. The adsorption kinetics and isotherm fitting results show that the adsorption of CMT on CS NPs follows the pseudo-second-order kinetic model and the Langmuir isotherm adsorption model, with a maximum adsorption capacity of 1.67 mg g-1; the adsorption process is spontaneous and exothermic. Under optimal adsorption conditions, the drug loading capacity reaches 9.76%. In vitro simulated digestion experiments demonstrate that the total bioaccessibility of the CS NPs-CMT complex in simulated gastrointestinal environments is enhanced to 80%. Spectral analysis shows that, compared with free CMT, the interaction between CS NPs-CMT complex and bovine serum albumin (BSA) is significantly enhanced, manifesting as greater binding affinity (Kb = 5.57 × 106 M-1) and strong fluorescence quenching (quenching rate of 59.95%). The CS NPs-CMT complex induces more pronounced structural alterations in BSA (α-helix content decreases from 55.60% to 49.50%). Site-competition experiments reveal that free CMT primarily binds to Site II of BSA, whereas upon loading onto CS NPs, its binding site shifts to Site I. In addition, loading onto CS NPs partially alleviates the competitive inhibition of BSA esterase activity by CMT, while retaining the protective effect of CMT on BSA thiol groups.