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

Abstract

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-PEG₃₀₀₀-DOPE:BVE-PEG₃₀₀₀-DOPE ratio of 14:5:4:0.28:0.05, w/w; the hydration temperature of 41 °C; stripping using pH 7.5 sodium dihydrogen phosphate buffer; and ultrasound for 3 min (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 hyperplasia index (1.34 ± 0.51) and levels of VEGF, TGF-β₁ and TNF-α (30.90 ± 3.57, 733.2 ± 43.19 and 66.76 ± 2.98 ng·L⁻¹, respectively), compared to the model group (p < .01).

Keywords:

• Paeonol
• targeted immunoliposomes
• bevacizumab
• VEGF
• hypertrophic scar
• Box–Behnken design

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Additional information

Funding

We would like to thank Excellent Young Teachers Training Project in Higher Education of Guangdong [YQ2015099] and Guangdong natural science project [2018A0303130234] for funding this work.