The rigidity of nanoliposomes significantly influences their physical stability and in vitro and in vivo behaviors (e.g., cellular uptake, blood circulation, biodistribution, etc.). This study aimed to quantify the rigidity of the nanoliposomes composed of phytosterol with varying C3 branches and phospholipids (DPPC, DOPC) using atomic force microscopy. Young's modulus, determined by the Shell model, effectively differentiated between mechanical differences in nanoliposomes with varying components and component structure and phase states. FTIR results indicated that P-SG exhibited the highest Young's modulus (175.98 ± 10.53 MPa) due to the hydrogen bond between the glucose residue of steryl glycosides (SGs) and the phospholipid polar head. However, the rigidity of DOPC nanoliposomes was not significantly different due to the unsaturated bond. The addition of oligomeric proanthocyanidin (OPC) did not change the order of rigidity among the nanoliposomes, with P-SG-OPC having the highest Young's modulus (126.27 ± 2.06 MPa). In the simulated gastrointestinal tract experiment, P-SG-OPC exhibited the greatest stability, with minimal particle aggregation. Cellular uptake experiments revealed that DPPC nanoliposomes with high rigidity had optimal endocytosis, while DOPC nanoliposome uptake was independent of rigidity. In melanin production inhibition tests, the inhibitory effect correlated directly with Young's modulus and P-SG-OPC had the best inhibitory effect on melanin generation. Our findings in this study provide valuable insights into the design and optimization of nanoliposomes for the efficient delivery of active substances, offering potential solutions for improving the efficacy of drug delivery systems.
Keywords: Young’s modulus; atomic force microscope; endocytosis; nanoliposomes; phytosterol; rigidity.