Porous microspheres as promising vehicles for the topical delivery of poorly soluble asiaticoside accelerate wound healing and inhibit scar formation in vitro &in vivo.
Asiaticoside is a natural compound possessing diverse pharmacological effects with great potential for clinical use. However, the low solubility and oil-water partition coefficient of asiaticoside lead to reduced effect and limited application. This study aims to construct a porous microsphere for the sustained release of asiaticoside to improve its absorption and enhance the therapeutic effects. Parameters of the formulations, including the drug to polymer ratio, solvent amounts of the inner and external phases, the stirring speed for preparation, and the drug entrapment efficiency were investigated and optimized. Particle size, morphology, pores structure, and Fourier transform infrared spectrum of the microsphere were characterized. The release kinetics and cellular uptake profiles of the asiaticoside-microspheres were examined. The therapeutic effects of asiaticoside-microspheres on wound healing and skin appendages regeneration were investigated in vitro & in vivo. Results showed that the optimized asiaticoside-microspheres possess spherical spongy structure with cylindrical holes. Asiaticoside can be loaded in the microsphere with high efficiency and released with sustained manner. The cellular uptake of asiaticoside from the microspheres was increased with 9.1 folds higher than that of free solution. Asiaticoside-microspheres expressed the strong promotion in the proliferation, migration of keratinocytes and wound scratching healing in vitro. More importantly, they significantly accelerated the re-epithelization, collagen synthesis and pro-angiogenesis in the rat full-skin wound healing. Porous microsphere was shown a novel carrier for the sustained delivery of poorly soluble asiaticoside, with absorption and therapeutic effects improved. Asiaticoside-microsphere is a promising topical preparation with excellent regenerative effects for the wound therapy.
Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, PR China.
Chen-Zhen
CZ
Zhang
Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, PR China.
Jie
J
Niu
Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, PR China.
Yee-Song
YS
Chong
Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, PR China.
Yan-Fen
YF
Huang
Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, PR China.
Yang
Y
Chu
Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, PR China; Pharmacy Division, Zhejiang Provincial Hospital of Traditional Chinese Medicine, Hangzhou, PR China.
Sheng-Yang
SY
Xie
State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau.
Zhi-Hong
ZH
Jiang
Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, PR China; State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau. Electronic address: lhpeng@zju.edu.cn.
Li-Hua
LH
Peng
D000287:Administration, Topical; D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage; D002465:Cell Movement; D049109:Cell Proliferation; D002921:Cicatrix / Q000188:drug therapy*; D003094:Collagen / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D015603:Keratinocytes / Q000166:cytology; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D010316:Particle Size; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D016062:Porosity; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000187:drug effects / Q000378:metabolism; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D013499:Surface Properties; D014315:Triterpenes / Q000008:administration & dosage*; D014867:Water / Q000737:chemistry; D014945:Wound Healing
D000890:Anti-Infective Agents; D004337:Drug Carriers; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D014315:Triterpenes; D014867:Water; D003094:Collagen; C004446:asiaticoside
Poorly soluble asiaticoside; Porous microsphere; Topical delivery; Wound healing