The efficacy of anti-VEGF antibody-modified liposomes loaded with paeonol in the prevention and treatment of hypertrophic scars

摘要

The aim of this study was to investigate the efficacy of anti-VEGF antibody-modified Paeonol liposome gels (PAE-BEV-lip gels) in the prevention and treatment of hypertrophic scars (HS). Systematic optimization of the encapsulation process of anti-VEGF antibody-modified Paeonol liposomes (PAE-BEV-lips) was performed using Box-Behnken design with the optimized parameters as follows: SPC concentration of 7.36 mg mL-1- SPC-Chol-PAE:pNP-PEG3ooo-DOPE:BVE-PEG3ooo-DOPE ratio of 14:5:4:0.28:0.05, w/w; the hydra-tion temperature of 41 °C; stripping using pH 7.5 sodium dihydrogen phosphate buffer; and ultrasound for 3min (ultrasound time 2 s, interval 3 s, power 300 W). Using these conditions, the encapsulation efficiency of PAE reached the peak level, i.e. 73.61 ±2.36%. The PAE-BEV-lips displayed unimodal size-distribution with a mean diameter of (235.7 ±4.67) nm and a zeta potential of-(5.13 ±0.25) mV. The investigation of the retention effect PAE-BEV-lip gels revealed a slower transdermal delivery rate, a remarkable dermal retention effect, and superior bioavailability compared to PAE gels and PAE conventional liposome gels (PAE-lip gels). Meanwhile, PAE-BEV-lip gels exhibited definite effects on the prevention and treatment of HS of the rabbit ears. The PAE-BEV-lip gels group showed a lower scar proliferation rate, fewer and looser collagenous fibers and fibromyocytes, more regular chondrocytes, less calcified tissue and fewer inflammatory cells compared to other groups. At the same time, PAE-BEV-lip gels significantly reduced scar hyper-plasia index (1.34±0.51) and levels of VEGF, TGF-β1 and TNF-aα (30.90 ±3.57, 733.2 ±43.19 and 66.76±2.98ng-L-1, respectively), compared to the model group (p<.01).