Loading Psoralen into liposomes to enhance its stimulatory effect on the proliferation and differentiation of mouse calvarias osteoblasts

Abstract

Psoralen (PSR), a well-known traditional Chinese medicine has been claimed for the treatment of osteoporosis. However, its hydrophobicity and the first-pass metabolism restrict the potential application of PSR. Thus, the development of PSR-loaded liposome was done to improve the solubility and bioavailability of PSR. The PSR/liposomes exhibited a particle size of approximately 110 nm and were quite stable during 30 days of storage. The entrapment efficiency (EE), drug loading (DL) and zeta potentials of PSR/liposome were 85.0 ± 1.6%, 5.0 ± 1.6% and -36 mV, respectively. Small angle X-ray scattering (SAXS) and transmission electron microscopy (TEM) measurements suggested that PSR/liposomes are the mixture of unilamellar and multilamellar vesicles. The in vitro drug release profile of PSR/liposome exhibited a gradual behavior. Both pure PSR and PSR/liposome promoted osteoblast proliferation in a dose-dependent manner. The proliferation effect was firstly enhanced with drug concentration increased, and then decreased when the concentration was higher than 20 µM. But PSR/liposome could induce osteoblast proliferation in more gentle way through the sustained release of PSR. For the level of ALP activity, PSR/liposome was 1.2 times higher than pure PSR. Above all, it is expected that PSR/liposome could be used in osteoporosis treatment in the future.

Graphical Abstract

Keywords:

• Differentiation
• liposome
• osteoporosis
• proliferation
• psoralen

Acknowledgements

Thanks to the staff of the BL19U2 beamline at the National Center for Protein Science Shanghai and the Shanghai Synchrotron Radiation Facility for assistance during data collection.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China (Grant No. 21573070, 21872051, U1832144).