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Drug Dev Ind Pharm. 2018 Dec 4:1-29. doi: 10.1080/03639045.2018.1546315. [Epub ahead of print]

The Efficacy of Anti-VEGF Antibody-Modified Liposomes Loaded with Paeonol in the Prevention and Treatment of Hypertrophic Scars.

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1
a Department of Chinese Medicine , Guangdong Pharmaceutical University of China , Guangzhou , Guangdong , China.

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 (HSs). 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 HSs 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 < 0.01).

KEYWORDS:

Bevacizumab; Box-Behnken Design; Hypertrophic Scar; Paeonol; Targeted immunoliposomes; VEGF

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