title: Hypolipidemic potential of perillaldehyde-loaded self-nanoemulsifying delivery system in high-fat diet induced hyperlipidemic mice: Formulation, in vitro and in vivo evaluation.
abstract: This study reports the hypolipidemic effects of perillaldehyde-loaded self-nanoemulsifying delivery system (PAH-SNEDS) developed with D-optimal experimental design based on a three component system: 40% w/w drug-oil phase, X1 (a mixture of perillaldehyde-isopropyl myristate/medium chain triglyceride, 1:1, w/w); 48% surfactant, X2 (Kolliphor EL); and 12% co-surfactant, X3 (PEG 200). The design space was navigated using a linear model to produce spherical and homogenous droplets which were observed under TEM, with mean size, polydispersity index (PDI) and zeta potential of 32.8 ± 0.1 nm, 0.270 ± 0.029 and -10.14 ± 0.66 mV, respectively. PAH-SNEDS demonstrated significant increase in dissolution in vitro compared to the free PAH, and further yielded an oral relative bioavailability of about 206.18% in vivo which suggested a promising formulation design for potential liquid bioactive compounds. Oral administration of PAH-SNEDS (240 mg/kg per body weight) in high-fat induced hyperlipidemia in mice, also significantly decreased serum total cholesterol (TC), triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C) while increasing high-density lipoprotein cholesterol (HDL-C) level. The improved bioavailability and functional application of PAH via SNEDDS suggested a suitable approach to promote hypolipidemic effect of the drug. Perillaldehyde, therefore, promises to be a useful bioactive compound to prevent high-fat diet induced hyperlipidemia.
authors: Department of Pharmaceutics, School of Pharmacy, Center for Nano Drug/Gene Delivery and Tissue Engineering, Jiangsu University, Zhenjiang 212013, People's Republic of China; Department of Pharmaceutical Sciences, Kumasi Polytechnic, P.O. Box 854, Kumasi-Ghana.
authors: Emmanuel
authors: E
authors: Omari-Siaw
authors: Department of Pharmaceutics, School of Pharmacy, Center for Nano Drug/Gene Delivery and Tissue Engineering, Jiangsu University, Zhenjiang 212013, People's Republic of China.
authors: Yuan
authors: Y
authors: Zhu
authors: Department of Pharmaceutics, School of Pharmacy, Center for Nano Drug/Gene Delivery and Tissue Engineering, Jiangsu University, Zhenjiang 212013, People's Republic of China.
authors: Houyong
authors: H
authors: Wang
authors: Department of Pharmaceutics, School of Pharmacy, Center for Nano Drug/Gene Delivery and Tissue Engineering, Jiangsu University, Zhenjiang 212013, People's Republic of China.
authors: Wei
authors: W
authors: Peng
authors: Department of Pharmaceutics, School of Pharmacy, Center for Nano Drug/Gene Delivery and Tissue Engineering, Jiangsu University, Zhenjiang 212013, People's Republic of China.
authors: Caleb Kesse
authors: CK
authors: Firempong
authors: Department of Pharmaceutics, School of Pharmacy, Center for Nano Drug/Gene Delivery and Tissue Engineering, Jiangsu University, Zhenjiang 212013, People's Republic of China.
authors: Yuan Wen
authors: YW
authors: Wang
authors: Department of Pharmaceutics, School of Pharmacy, Center for Nano Drug/Gene Delivery and Tissue Engineering, Jiangsu University, Zhenjiang 212013, People's Republic of China.
authors: Xia
authors: X
authors: Cao
authors: Department of Pharmaceutics, School of Pharmacy, Center for Nano Drug/Gene Delivery and Tissue Engineering, Jiangsu University, Zhenjiang 212013, People's Republic of China.
authors: Wenwen
authors: W
authors: Deng
authors: Department of Pharmaceutics, School of Pharmacy, Center for Nano Drug/Gene Delivery and Tissue Engineering, Jiangsu University, Zhenjiang 212013, People's Republic of China; School of Pharmacy, China Pharmaceutical University, Nanjing, People's Republic of China.
authors: Jiangnan
authors: J
authors: Yu
authors: Department of Pharmaceutics, School of Pharmacy, Center for Nano Drug/Gene Delivery and Tissue Engineering, Jiangsu University, Zhenjiang 212013, People's Republic of China. Electronic address: xmxu@ujs.edu.cn.
authors: Ximing
authors: X
authors: Xu
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical / Q000379:methods; D002784:Cholesterol / Q000097:blood; D059305:Diet, High-Fat / Q000009:adverse effects; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D004655:Emulsions / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D006949:Hyperlipidemias / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy*; D000960:Hypolipidemic Agents / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D008075:Lipoproteins, HDL / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D051379:Mice; D039821:Monoterpenes / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013501:Surface-Active Agents / Q000737:chemistry; D014280:Triglycerides / Q000097:blood
chemical_list: D004337:Drug Carriers; D004655:Emulsions; D000960:Hypolipidemic Agents; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D039821:Monoterpenes; D013501:Surface-Active Agents; D014280:Triglycerides; C033342:perillaldehyde; D002784:Cholesterol
keywords: Bioavailability; Formulation; Hypolipidemic activity; Liquid bioactive; Perillaldehyde; Self-nanoemulsifying