Nanotechnology promotes the full-thickness diabetic wound healing effect of recombinant human epidermal growth factor in diabetic rats

被引:93
作者
Chu, Yuejie [1 ]
Yu, Demin [1 ]
Wang, Penghua [1 ]
Xu, Jun [1 ]
Li, Daiqing [1 ]
Ding, Min [1 ]
机构
[1] Tianjin Med Univ, Metab Dis Hosp, Dept Diabet Foot, Tianjin 300070, Peoples R China
关键词
FOOT ULCERS; PLGA MICROSPHERES; STABILITY; RELEASE; PROTEIN;
D O I
10.1111/j.1524-475X.2010.00612.x
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
We utilized a modified double-emulsion method with poly(lactic-co-glycolic acid) as the carrier to prepare recombinant human epidermal growth factor (rhEGF) nanoparticles. The morphology of the nanoparticles was detected by a transmission electron microscope. The particle size distribution was measured by a laser analyzer with a zeta potential meter. Enzyme-linked immunosorbent assays were performed to determine the rhEGF encapsulation efficiency and release model, and the proliferation of the mouse fibroblasts was analyzed by the MTT method. Diabetic rats with full-thickness wounds were divided into four groups according to different treatments: rhEGF nanoparticles, rhEGF stock solution, empty nanoparticles, and phosphate-buffered saline. Photographs were taken after the treatments to calculate the wound healing rates, and the granulation tissue of the wounds was sampled for pathologic slides. Proliferating cell nuclear antigen was assayed by immunohistochemistry. Our results showed that the rhEGF nanoparticles were around 193.5 nm (diameter), and the particle size distribution was uniform and dispersible. The encapsulation efficiency was 85.6% and rhEGF release lasted 24 hours. Compared with other groups, the rhEGF nanoparticles promoted the highest level of fibroblast proliferation, and this group showed the fastest healing rate. The number of proliferating cell nuclear antigen positive cells in the rhEGF nanoparticles group was higher than the other groups. We concluded that controlled release of rhEGF encapsulated in the nanoparticles enhanced rhEGF effects to stimulate cell proliferation and shorten the wound healing time.
引用
收藏
页码:499 / 505
页数:7
相关论文
共 21 条
[1]  
Albert Stephen, 2002, Clin Podiatr Med Surg, V19, P483, DOI 10.1016/S0891-8422(02)00018-6
[2]   Biodegradation and biocompatibility of PLA and PLGA microspheres [J].
Anderson, JM ;
Shive, MS .
ADVANCED DRUG DELIVERY REVIEWS, 1997, 28 (01) :5-24
[3]   Growth factors in the treatment of diabetic foot ulcers [J].
Bennett, SP ;
Griffiths, GD ;
Schor, AM ;
Leese, GP ;
Schor, SL .
BRITISH JOURNAL OF SURGERY, 2003, 90 (02) :133-146
[4]   Development of poly-(D,L-lactide-coglycolide) microsphere formulations containing recombinant human vascular endothelial growth factor to promote local angiogenesis [J].
Cleland, JL ;
Duenas, ET ;
Park, A ;
Daugherty, A ;
Kahn, J ;
Kowalski, J ;
Cuthbertson, A .
JOURNAL OF CONTROLLED RELEASE, 2001, 72 (1-3) :13-24
[5]  
Fernandez-Montequin Jose I, 2007, Int Wound J, V4, P333
[6]   Expression of apoptosis- and cell cycle-related proteins in epidermis of venous leg and diabetic foot ulcers [J].
Galkowska, H ;
Olszewski, WL ;
Wojewodzka, U ;
Mijal, J ;
Filipiuk, E .
SURGERY, 2003, 134 (02) :213-220
[7]   Chemokines, cytokines, and growth factors in keratinocytes and dermal endothelial cells in the margin of chronic diabetic foot ulcers [J].
Galkowska, Hanna ;
Wojewodzka, Urszula ;
Olszewski, Waldemar L. .
WOUND REPAIR AND REGENERATION, 2006, 14 (05) :558-565
[8]   Quality of life of adults with unhealed and healed diabetic foot ulcers [J].
Goodridge, D ;
Trepman, E ;
Sloan, J ;
Guse, L ;
Strain, LA ;
McIntyre, J ;
Embil, JM .
FOOT & ANKLE INTERNATIONAL, 2006, 27 (04) :274-280
[9]  
HE C, 2001, WOUND REPAIR REGEN, V9, P305
[10]   Lysozyme stability in primary emulsion for PLGA microsphere preparation: Effect of recovery methods and stabilizing excipients [J].
Kang, FR ;
Jiang, G ;
Hinderliter, A ;
DeLuca, PP ;
Singh, J .
PHARMACEUTICAL RESEARCH, 2002, 19 (05) :629-633