Protective effect of FGF-2 and low-molecular-weight heparin/protamine nanoparticles on radiation-induced healing-impaired wound repair in rats

Abstract

We examined the effectiveness of localized administration of fibroblast growth factor-2 containing low-molecular-weight heparin/protamine nanoparticles (FGF-2&LMWH/P NPs) on apoptosis in vivo and on healing of radiation-induced skin injury in a rat model. FGF-2 binds onto LMWH/P NPs, which can significantly enhance and stabilize FGF-2 as a local carrier. X-irradiation at a dose of 25 Gy was administered to the lower part of the back (using a lead sheet with two holes) 1 h before the administration of FGF-2&LMWH/P NPs. Cutaneous full-thickness defect wounds were then formed in X-irradiated areas to examine the time-course of wound healing, and the wound tissues were microscopically and histologically compared and examined. Wound healing was significantly delayed by X-irradiation, but FGF-2&LMWH/P NPs administration prior to irradiation led to a significantly shorter delay compared with FGF-2 alone, LMWH/P NPs alone, and controls. Furthermore, terminal deoxynucleotidyl transferase–mediated dUTP nick-end labeling (TUNEL) staining showed that the proportions of apoptotic dermal fibroblasts in X-irradiated skin were significantly lower in rats administered FGF-2&LMWH/P NPs than in controls. However, 8-hydroxy-2’-deoxyguanosine (8-OHdG) staining showed no differences. Thus, localized administration of FGF-2&LMWH/P NPs prior to irradiation may alleviate X-irradiation-induced healing-impaired wound repair in normal tissue.

Human Fibroblast Gene Expression Modulation Using 940 NM Diode Laser

“…FGF promotes fibroblast mitogenesis, favoring the formation of granulation tissue and promoting re-epithelization and damaged tissue remodeling 16 . Both of our treatments with 940 nm diode laser (single dose or two doses) significantly increased FGF expression, although the effect was lower with two doses.…”

Rational Design of Nanomaterials for Various Radiation‐Induced Diseases Prevention and Treatment

“…Skin diseases. [ 34 ] Salivary gland diseases: Adapted with permission. [ 35 ] Copyright 2013, Elsevier Inc.…”

“…However, free FGF‐2 is sensitive to proteolytic enzymes and heat. In a simulation environment of 37 °C and pH 7.4 in vivo, its half‐life is approximately or even less than 12 h. [ 34,88 ] Thus, a sufficient concentration of gene drugs needs to be maintained locally and to maintain a sustained release while retaining activity. Nanomaterials with good drug‐loading capacity can effectively address the above issues.…”

“…bound FGF‐2 onto low molecular‐weight heparin/protamine NPs (LMWH/P NPs, as a local carrier) to form the nanocomplex FGF‐2&LMWH/P NPs, which was delivered into skin by subcutaneous administration before X‐irradiation. [ 34 ] This design not only significantly increased the stability of FGF‐2, but was also beneficial for stabilizing, activating and gradually releasing FGF‐2 from FGF‐2&LMWH/P NPs. According to the experimental results, the wound healing of rats in the FGF‐2&LMWH/P NPs + X‐irradiation group showed a shorter delay compared to that of the FGF‐2 alone, the LMWH/P NPs alone, and the X‐ray alone groups.…”

Low-Molecular-Weight Heparins: Reduced Size Particulate Systems for Improved Therapeutic Outcomes

“…Encapsulation has played an important role in the synthesis of drug delivery systems, including micro- and nano-particles [ 23 , 24 , 25 , 26 , 27 ]. These modalities are useful for protecting a drug from the environment [ 28 ]; controlling the release of a drug [ 28 , 29 , 30 , 31 , 32 ]; and delivering a drug at the desired target site, providing improved therapeutic outcomes [ 33 ].…”