Sequential release of salidroside and paeonol from a nanosphere-hydrogel system inhibits ultraviolet B-induced melanogenesis in guinea pig skin

Abstract

Melanin is the one of most important pigments for skin color in mammals. Excessive biosynthesis of melanin induces various pigment disorders. Much effort has been made to develop regulators to minimize skin pigmentation abnormalities. However, only a few of them are used, primarily because of safety concerns and low efficiency. In this study, we aimed to construct a novel nanosphere-gel for sequential delivery of salidroside and paeonol, to investigate the synergistic effects of these drugs in anti-melanogenesis, and to decrease their potential for toxicity in high dosage. Nanospheres were prepared and characterized for their particle size, polydispersity index, zeta potential, and morphological properties. The optimized nanospheres were incorporated in carbomer hydrogel with both paeonol and salidroside entrapped to form a dual drug-releasing nanosphere-gel. With this nanosphere-gel, rapid release of salidroside from the hydrogel followed by sustained release of paeonol from the nanosphere was achieved. Using a classical model of the melanogenesis response to ultraviolet exposure, it was shown that the anti-melanogenesis effects of the dual drug-releasing system, in which the doses of the individual drugs were decreased by half, was obviously enhanced when compared with the effects of the single drug preparations. Mechanistically, the burst release of salidroside from the hydrogel may enable prompt suppression of melanocyte proliferation on exposure to ultraviolet B radiation, while the paeonol released in a sustained manner can provide continuous inhibition of tyrosinase activity in melanocytes. Combined delivery of salidroside and paeonol was demonstrated to be a promising strategy for enhancing the therapeutic efficacy of these agents in anti-melanogenesis and reducing their toxicity, so may have great potential in nanomedicine.

Resveratrol-Enriched Rice Down-Regulates Melanin Synthesis in UVB-Induced Guinea Pigs Epidermal Skin Tissue

“…UVB-irradiated guinea pigs, a commonly used animal model for hyperpigmentation research, were used for the in vivo experiments reported herein ( Kim et al ., 2008 ; Fujii et al ., 2011 ; Peng et al ., 2014 ). All were treated with a dose of 1% (w/v) sample.…”

Therapeutic potential of phenylethanoid glycosides: A systematic review

“…Compared with treatments of paeonol-loaded nanosphere dispersion and salidroside-loaded hydrogel, the nanosphere-hydrogel formulation with paeonol and salidroside decreased the melanin levels to a larger extent in guinea pig skin induced by UV B. 268 Besides that, niosomes were also applied as transdermal nanocarriers in salidroside to enhance its transdermal delivery. 269 Niosomes have the advantage of less susceptible to oxidation, more stable, and less costly.…”

Tyrosinase-based TLC Autography for anti-melanogenic drug screening

“…For anti-melanogenic drugs screening, various methods have been established from in vitro to in vivo assays. Currently, ultraviolet-induced hyperpigmentation in guinea pig and phenotype-based zebrafish are animal models both widely applied to evaluate the effects of candidate drugs for the inhibition of melanogenesis 3 , 4 . However, in vivo animal models often requires long experimental periods and extensive work, not to mention the considerable consumption of testing drugs used in animals for large-scale screening 5 .…”