Development and evaluation of nanocarriers of β-lactoglobulin for drug delivery: a comparative study of protein-based nanoparticle, nanofiber, and nanotube

Smart drug delivery systems utilizing nanocarriers offer precise control over the timing, location, and rate of drug release in response to external stimuli such as pH and temperature. This study investigated β-lactoglobulin, a biocompatible and stable protein, as a material for developing pH-responsive nanocarriers, including nanoparticles, nanofibrils, and nanotubes, synthesized via temperature- and pH-dependent aggregation without cross-linking agents. Various analytical techniques, including microscopic imaging, CD, FTIR and UV–Vis and fluorescence spectroscopy, and drug-binding and release assays, were employed to evaluate the nanostructures’ performance across different pH levels. The findings revealed that all β-lactoglobulin nanostructures were highly pH-responsive, with maximum vancomycin loading capacity observed at pH 7.4. Among the nanocarriers, nanotubes exhibited the highest drug-loading efficiency, followed by nanofibrils and nanoparticles. Notably, nanofibrils at pH 7.4 demonstrated the lowest drug release rate, followed by nanotubes, indicating their superior stability in drug release. Vancomycin retained its structural and functional stability post-release, as confirmed by antimicrobial testing. These results underscore the potential of tubular and fibrillar β-lactoglobulin nanostructures as promising candidates for the controlled and stable delivery of vancomycin, offering opportunities for further optimization and application in smart drug delivery systems.