Preparation and evaluation of Baicalin-loaded albumin nanoparticles for anti-breast cancer activity.

BACKGROUND

Baicalin (BA), a natural flavonoid compound, exhibits potential anti-breast cancer (BC) activity. However, its therapeutic efficacy is limited by biological membrane and tumor barriers. Albumin nanoparticles demonstrate excellent biocompatibility and ease of modification, making them highly advantageous for antitumor drug delivery. Despite these advantages, current preparation methods for albumin-based NPs have significant limitations, including the use of organic or toxic reagents, large and uneven particle size products, complex processes, etc. OBJECTIVE: The purpose of this study was to develop a novel method for preparing albumin nanoparticles (BSA NPs). Subsequently, BSA NPs were modified with folic acid (FA) and polymers and loaded with BA to construct a novel nanodrug delivery system (BA@mPEG-FA-BSA NPs) to improve the anti-breast cancer efficacy of BA.

METHODS

Compared with the desolvation method and the thermal gelation method, the advantages of the new preparation method of BSA NPs are: less organic solvent and preparation time, greater yield, smaller particle size and uniform product. The preparation method of BSA NPs was investigated by single factor experiment. The encapsulation efficiency (EE) and drug loading (DL) of BA in BA@mPEG-FA-BSA NPs were detected by HPLC. The structural composition and physicochemical properties of the nanoparticles were characterized using transmission electron microscopy (TEM), infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA), and X-ray diffraction (XRD). The anti-breast cancer efficacy of BA@mPEG-FA-BSA NPs was evaluated through cellular uptake, cytotoxicity, apoptosis, cell cycle analysis, and in vivo tumor-bearing mouse studies.

RESULTS

According to the setting of process parameters, the established method can control the acquisition of uniform BSA NPs with a particle size between 20 and 300 nm. BA@mPEG-FA-BSA NPs exhibited a particle size of approximately 59.26 nm, a polydispersity index (PDI) < 0.3, EE of about 46.7 %, and DL of approximately 2.6 %. Cellular uptake experiments demonstrated that mPEG-FA-BSA NPs enhanced the uptake of free coumarin 6 in BT20 cells, with free FA showing competitive inhibition effects. Efficacy evaluation revealed that BA@mPEG-FA-BSA NPs exhibited cytotoxicity against BT20 cells, induced cell cycle arrest and apoptosis, and inhibited tumor growth in 4 T1 tumor-bearing mice. In most cases, the effects of BA@mPEG-FA-BSA NPs were superior to those of free BA, with a concentration- or dose-dependent manner observed.

CONCLUSION

This study established a novel preparation method for albumin nanoparticles, providing a new methodology for the construction of nano-drug delivery systems based on albumin materials. The developed BA@mPEG-FA-BSA NPs, with their relatively small particle size, demonstrated enhanced cellular uptake and anti-breast cancer activity of BA, highlight the potential for further optimization and clinical translation.