2022, Vol. 26 ›› Issue (31): 4996-5001

Preparation of wogonoside polycaprolactone-polyethylene glycol micelles delivered by adipose stem cells

Wang Xiao1, Liu Qing1, Hu Yaorui1, Gu Chengxu1, Guo Qixuan1, Zhu Yonglin2, Zhang Luping1   

Abstract: BACKGROUND: Wogonoside has been proven to have anti-inflammatory, neuroprotective and other pharmacological activities. Wogonoside is difficult to dissolve in water and has a short half-life. In an organic solvent, wogonoside may bring patients with serious adverse reactions. Polycaprolactone-polyethylene glycol can combine highly hydrophobic drugs and achieve sustained release, but cannot accurately target the lesion. Micelles, because of their small size, can penetrate cell membranes.
OBJECTIVE: To prepare wogonoside polycaprolactone-polyethylene glycol micelles and adipose stem cells as a carrier to deliver wogonoside polycaprolactone-polyethylene glycol micelles so as to overcome the insolubility and short half-life of wogonoside and enable the drug to target the damage site.
METHODS: Wogonoside polycaprolactone-polyethylene glycol micelles were prepared by dialysis method and characterized. Encapsulation rate, drug loading and in vitro drug release rate were detected. SD rat adipose stem cells were prepared by collagenase digestion. The expression of CD90, CD44, and CD45 was detected by flow cytometry, immunohistochemistry, and immunofluorescence. After 14 days of adipocytes induction, oil red O staining was performed. CCK8 assay was used to detect cytotoxicity of wogonoside polycaprolactone-polyethylene glycol micelles to adipose stem cells. The micelles of coumarin 6 and wogonoside were co-incubated with adipose stem cells for cell localization.
RESULTS AND CONCLUSION: (1) The wogonoside polycaprolactone-polyethylene glycol micelles had a mean particle size of (26.7±0.4) nm, a Zeta potential of (-33.2±0.3) mV, and a relatively uniform shape of round ball. (2) The encapsulation rate of wogonoside polycaprolactone-polyethylene glycol micelles was (90.2±2.04)% and the drug loading was (9.18±0.31)%. (3) The cumulative release rate of free wogonoside was 98% for 24 hours, and that of wogonoside polycaprolactone-polyethylene glycol micelles was 87% for 96 hours. (4) Flow cytometry, immunohistochemistry, and immunofluorescence showed that CD90 and CD44 were highly expressed, while CD45 was almost not. Oil red O staining showed red droplets after lipid induction. (5) CCK8 assay showed that the micellar mass concentration in the range of 10-200 mg/L had no effect on cells. (6) Confocal laser confocal results showed that coumarin 6 and wogonoside polycaprolactone-polyethylene glycol micelles could enter the mitochondria of adipose stem cells. (7) The results showed that the wogonoside polycaprolactone-polyethylene glycol micelles could enter adipose stem cells, and adipose stem cells could carry wogonoside polycaprolactone-polyethylene glycol micelles.   wogonoside; polycaprolactone; polyethylene glycol; micelles; characterization; in vitro release; adipose stem cells
Key words: wogonoside, polycaprolactone, polyethylene glycol, micelles, characterization, in vitro release, adipose stem cells