title: Combination of hydrotropic nicotinamide with nanoparticles for enhancing tacrolimus percutaneous delivery.
abstract: Tacrolimus (FK506), an effective immunosuppressant for treating inflammatory skin diseases, hardly penetrates into and through the skin owing to its high hydrophobicity and molecular weight. The aim of this study was to develop a hybrid system based on nicotinamide (NIC) and nanoparticles (NPs) encapsulating FK506, such as FK506-NPs-NIC, for facilitating percutaneous delivery, which exploited virtues of both NIC and NPs to obtain the synergetic effect. Solubility and percutaneous permeation studies were carried out. The results showed that NIC could increase the solubility and permeability of FK506 and that 20% (w/v) NIC presented higher FK506 permeability and was thus chosen as the hydrotropic solution to solubilize FK506 and prepare FK506-NPs-NIC. Hyaluronic acid (HA) was chemically conjugated with cholesterol (Chol) to obtain amphiphilic conjugate of HA-Chol, which self-assembled NPs in 20% NIC solution containing FK506. The particle size, zeta potential, and morphology of NPs were characterized. The encapsulation efficiency and in vitro percutaneous permeation of NPs were evaluated in the presence and absence of NIC. The results demonstrated that hydrotropic solubilizing FK506 was readily encapsulated into NPs with a higher encapsulation efficiency of 79.2%±4.2%, and the combination of NPs with NIC exhibited a significantly synergistic effect on FK506 deposition within the skin (2.39±0.53 μg/cm(2)) and penetration through the skin (13.38±2.26 μg/cm(2)). The effect of the combination of NPs with NIC on drug permeation was further visualized by confocal laser scanning microscope through in vivo permeation studies, and the results confirmed that NPs-NIC synergistically enhanced the permeation of the drug into the skin. The cellular uptake performed in HaCaT cells presented a promoting effect of NPs on cellular uptake. These overall results demonstrated that HA-Chol-NPs-NIC can synergistically improve the percutaneous delivery of FK506, and it is a novel potential strategy based on a nano-sized carrier for FK506 to treat skin diseases.
authors: Department of Pharmaceutics, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors: Wenhui
authors: W
authors: Pan
authors: Department of Pharmaceutics, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors: Mengyao
authors: M
authors: Qin
authors: Department of Pharmaceutics, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors: Guoguang
authors: G
authors: Zhang
authors: Department of Pharmaceutics, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors: Yueming
authors: Y
authors: Long
authors: Department of Pharmaceutics, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors: Wenyi
authors: W
authors: Ruan
authors: Department of Pharmaceutics, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors: Jingtong
authors: J
authors: Pan
authors: Department of Pharmaceutics, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors: Zushuai
authors: Z
authors: Wu
authors: Department of Pharmaceutics, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors: Tao
authors: T
authors: Wan
authors: Department of Pharmaceutics, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors: Chuanbin
authors: C
authors: Wu
authors: Department of Pharmaceutics, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors: Yuehong
authors: Y
authors: Xu
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004337:Drug Carriers / Q000737:chemistry*; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D008297:Male; D018613:Microscopy, Confocal; D008970:Molecular Weight; D053758:Nanoparticles / Q000737:chemistry*; D009536:Niacinamide / Q000008:administration & dosage*; D010316:Particle Size; D010539:Permeability; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin; D012995:Solubility; D016559:Tacrolimus / Q000008:administration & dosage*
chemical_list: D004337:Drug Carriers; D007166:Immunosuppressive Agents; D009536:Niacinamide; D006820:Hyaluronic Acid; D016559:Tacrolimus
keywords: hyaluronic acid; nanoparticles; nicotinamide; percutaneous delivery; tacrolimus