Wei Wei1, Xiaonan Lu2, Zegao Wang3, Bianca Pérez2, Jingying Liu4, Chengyu Wu4, Mingdong Dong3, Fengqin Feng5, Huiling Mu4, Zheng Guo6. 1. Department of Engineering, Faculty of Science and Technology, Aarhus University, 8000 Aarhus, Denmark; Zhejiang Key Laboratory for Agro-Food Processing, College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou 310058, China; State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi 214122, China. 2. Department of Engineering, Faculty of Science and Technology, Aarhus University, 8000 Aarhus, Denmark. 3. Interdisciplinary Nanoscience Center, Aarhus University, 8000 Aarhus, Denmark. 4. Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, 2100 Copenhagen, Denmark. 5. Zhejiang Key Laboratory for Agro-Food Processing, College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou 310058, China. Electronic address: fengfq@zju.edu.cn. 6. Department of Engineering, Faculty of Science and Technology, Aarhus University, 8000 Aarhus, Denmark. Electronic address: guo@eng.au.dk.
Abstract
HYPOTHESIS: Synthetic sugar alcohol mono-behenates with high melting points, surface activity and resistance to enzymatic lipolysis, are expected to form stable single-component solid lipid nanocarriers (SC-SLNs). The preparation methods and the polar head group of the molecules should affect the size and drug encapsulation efficiency. EXPERIMENTS: SC-SLNs of sugar alcohol mono-behenates with varied polar heads were prepared using emulsification-diffusion method and melting-probe sonication method. Model lipophilic drug fenofibrate was formulated into nanocarriers. The drug release was assessed using the lipolysis model. The structure and drug distribution of the nanocarriers were studied using AFM and TEM. FINDINGS: Both the polar head group of the molecules and the preparation methods affect the particle size and size distribution. Nanocarriers prepared with sorbitol mono-behenates showed the smallest mean size (∼100nm with PdI of 0.26). In addition, they displayed high entrapment efficiency of fenofibrate (95%) and long term drug release. Nanocarriers prepared by emulsification-diffusion method entrapped fenofibrate into lipid bilayers. In contrast, Nanocarriers prepared by melting-probe sonication method had a micelle structure with fenofibrate incorporated into a lipid monolayer. This study provides an insight into the systematic development of novel amphiphilic lipids for solid lipid-based drug delivery system.
HYPOTHESIS: Synthetic sugar alcohol mono-behenates with high melting points, surface activity and resistance to enzymatic lipolysis, are expected to form stable single-component solid lipid nanocarriers (SC-SLNs). The preparation methods and the polar head group of the molecules should affect the size and drug encapsulation efficiency. EXPERIMENTS: SC-SLNs of sugar alcohol mono-behenates with varied polar heads were prepared using emulsification-diffusion method and melting-probe sonication method. Model lipophilic drug fenofibrate was formulated into nanocarriers. The drug release was assessed using the lipolysis model. The structure and drug distribution of the nanocarriers were studied using AFM and TEM. FINDINGS: Both the polar head group of the molecules and the preparation methods affect the particle size and size distribution. Nanocarriers prepared with sorbitol mono-behenates showed the smallest mean size (∼100nm with PdI of 0.26). In addition, they displayed high entrapment efficiency of fenofibrate (95%) and long term drug release. Nanocarriers prepared by emulsification-diffusion method entrapped fenofibrate into lipid bilayers. In contrast, Nanocarriers prepared by melting-probe sonication method had a micelle structure with fenofibrate incorporated into a lipid monolayer. This study provides an insight into the systematic development of novel amphiphilic lipids for solid lipid-based drug delivery system.