Sequential release of salidroside and paeonol from a nanosphere-hydrogel system inhibits ultraviolet B-induced melanogenesis in guinea pig skin.
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.
Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, People's Republic of China.
Li-Hua
LH
Peng
Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, People's Republic of China.
Shen-Yao
SY
Xu
Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, People's Republic of China.
Ying-Hui
YH
Shan
Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, People's Republic of China.
Wei
W
Wei
Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, People's Republic of China.
Shuai
S
Liu
Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, People's Republic of China.
Chen-Zhen
CZ
Zhang
Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, People's Republic of China.
Jia-He
JH
Wu
Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, People's Republic of China.
Wen-Quan
WQ
Liang
Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, People's Republic of China ; Novel Transdermal Research Center of Jiangsu Province, Changzhou, People's Republic of China.
Jian-Qing
JQ
Gao
D000287:Administration, Topical; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003692:Delayed-Action Preparations / Q000008:administration & dosage* / Q000737:chemistry; D003879:Dermatologic Agents / Q000008:administration & dosage / Q000138:chemical synthesis; D004058:Diffusion; D004338:Drug Combinations; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage* / Q000737:chemistry; D005960:Glucosides / Q000008:administration & dosage* / Q000737:chemistry; D006168:Guinea Pigs; D020100:Hydrogels / Q000737:chemistry; D008543:Melanins / Q000096:biosynthesis*; D008544:Melanocytes / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects*; D053769:Nanocapsules / Q000008:administration & dosage* / Q000737:chemistry / Q000648:ultrastructure; D054118:Nanospheres / Q000008:administration & dosage / Q000737:chemistry / Q000648:ultrastructure; D009381:Neoplasms, Radiation-Induced / Q000517:prevention & control*; D010636:Phenols / Q000008:administration & dosage* / Q000737:chemistry; D016896:Treatment Outcome; D014466:Ultraviolet Rays
D003692:Delayed-Action Preparations; D003879:Dermatologic Agents; D004338:Drug Combinations; D004365:Drugs, Chinese Herbal; D005960:Glucosides; D020100:Hydrogels; D008543:Melanins; D053769:Nanocapsules; D010636:Phenols; C524375:paeonal; C009172:rhodioloside
anti-melanogenesis; nanosphere; paeonol; salidroside; sequential drug release