title: Preparation of andrographolide-loaded solid lipid nanoparticles and their in vitro and in vivo evaluations: characteristics, release, absorption, transports, pharmacokinetics, and antihyperlipidemic activity.
abstract: Andrographolide (AND) is one of diterpenoids separated from Andrographis paniculata with a wide spectrum of biological activities of being anti-inflammatory, anticancer, hepatoprotective, and antihyperlipidemic. But its poor water solubility and instability resulted in lower bioavailability and seriously limited its pharmacological function. In this study, AND-loaded solid lipid nanoparticles (AND-SLNs) were prepared by a high-pressure homogenization method and presented as spherically shaped under transmission electron microscopy with an average diameter of 286.1 nm and zeta potential of -20.8 mV. The average drug-entrapment efficiency and drug loading were 91.00% and 3.49%, respectively. The results indicated that the lower bioavailability of AND is not only because of the poor solubility but also owing to its metabolic instability in intestinal segments. Furthermore, the transport mechanism of AND in Caco-2 cell model is complex in which an active transport carrier (P-glycoprotein) is involved in. The bioavailability and antihyperlipidemic activity of AND were improved by AND-SLNs by increasing the solubility and stability of AND in the intestine and by changing its transport mode in Caco-2 cell. The bioavailability of AND was increased to 241% by AND-SLNs as compared with AND suspension. AND-SLNs would be a promising drug-delivery system to enhance the oral absorption and bioavailability of AND.
authors.affiliation: The Ministry of Education Key Laboratory for Standardization of Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, The Institute of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People's Republic of China; Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People's Republic of China.
authors.forename: Tao
authors.initials: T
authors.lastname: Yang
authors.forename: Huan-Huan
authors.initials: HH
authors.lastname: Sheng
authors.forename: Nian-Ping
authors.initials: NP
authors.lastname: Feng
authors.forename: Hai
authors.initials: H
authors.lastname: Wei
authors.forename: Zheng-Tao
authors.initials: ZT
authors.lastname: Wang
authors.forename: Chang-Hong
authors.initials: CH
authors.lastname: Wang
mesh_terms: D035685:Andrographis / Q000737:chemistry; D000818:Animals; D018938:Caco-2 Cells; D004224:Diterpenes / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry*; D006801:Humans; D000960:Hypolipidemic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000494:pharmacology; D007408:Intestinal Absorption; D008055:Lipids / Q000097:blood / Q000737:chemistry*; D008297:Male; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D004224:Diterpenes; D004337:Drug Carriers; D000960:Hypolipidemic Agents; D008055:Lipids; C030419:andrographolide
keywords: Andrographolide; absorption; antihyperlipidemic activity; bioavailability; solid lipid nanoparticles; stability; transport