FGF-2-containing dalteparin/protamine nanoparticles (FGF-2&D/P NPs) ameliorate UV-induced skin photoaging in hairless mice

J Plast Surg Hand Surg. 2018 Dec;52(6):375-381. doi: 10.1080/2000656X.2018.1523178. Epub 2018 Nov 16.

Abstract

UVB exposure penetrates deeply into the dermis to alter skin barrier function, which is a primary factor in skin photoaging. We previously reported that dalteparin and protamine nanoparticles (D/P NPs) are effective carriers of FGF-2. This study aimed to examine the ability of FGF-2-containing D/P NPs (FGF-2&D/P NPs) to ameliorate UVB-induced skin photoaging in hairless mice. Dorsal skin of HR-1 hairless mice were exposed to UVB irradiation 5 days/week for 8 weeks (UV (+): final total, 2700 mJ/cm2). Mice were divided into four groups: Non-UVB (UV (-)) + saline, UV (+) + saline, UV (+) + FGF-2&D/P NPs, UV (+) + FGF-2, and UV (+) + D/P NPs, and following UVB irradiation, FGF-2&D/P NPs, FGF-2, and D/P NPs were applied to the groups of mice just after each UVB irradiation. Each group was subjected to evaluation of skin changes (elasticity), and histological examination using hematoxylin & eosin and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining. UVB irradiation of mice significantly induced a decline in elasticity and acanthosis, which was alleviated by application of FGF-2&D/P NPs. Furthermore, TUNEL-staining showed the proportions of apoptotic dermal fibroblast cells (DFCs) and epidermal keratinocyte cells (EKCs) in the UV (+) + FGF-2&D/P NPs group were significantly lower than those in the UV (+) + saline, UV (+) + FGF-2, and UV (+) + D/P NPs groups. Thus, FGF-2&D/P NPs may be effective in preventing skin photoaging accelerated by UVB irradiation such as declining elasticity, acanthosis, and apoptosis of DFCs and EKCs.

Keywords: D/P NP; FGF-2; UV-induced photoaging; apoptosis; skin.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Dalteparin / pharmacology*
  • Elasticity / drug effects
  • Fibroblast Growth Factor 2 / pharmacology*
  • Fibroblasts / metabolism
  • Fibroblasts / pathology
  • Keratinocytes / metabolism
  • Keratinocytes / pathology
  • Mice, Hairless
  • Nanoparticles*
  • Protamines / pharmacology*
  • Skin Aging / drug effects*
  • Skin Aging / radiation effects
  • Ultraviolet Rays / adverse effects*

Substances

  • Protamines
  • Fibroblast Growth Factor 2
  • Dalteparin