title: Development of intravenous lipid emulsion of α-asarone with significantly improved safety and enhanced efficacy.
abstract: Severe adverse events have been frequently associated with taking the commercially available formulation of α-asarone injection (α-asarone-I). Hence, we sought to develop an intravenous lipid emulsion of α-asarone (α-asarone-LE), where we hypothesized that these adverse events could be prevented. Using a central composite design-response surface methodology, we developed and optimized an emulsion formulation of α-asarone-LE that composed of 10.0% (w/v) soybean oil, 0.4% (w/v) α-asarone, 1.2% (w/v) soybean lecithin, 0.3% (w/v) F68, and 2.2% (w/v) glycerol. The mean particle size of α-asarone-LE was 226±11 nm, the ζ-potential was -25.6±1.2 mV, the encapsulation efficiency was 99.2±0.1% and the drug loading efficiency was 3.45%. Stability, safety, and efficacy studies of α-asarone-LE were systematically investigated and compared to those of α-asarone-I. The α-asarone-LE not only showed a desired stability, but also exhibited excellent safety and improved efficacy in vivo, indicating its great potential for clinical application in the future.
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education & West China School of Pharmacy, Sichuan University, No. 17, Section 3, Southern Renmin Road, Chengdu 610041, PR China.
authors.forename: Wei-Cong
authors.initials: WC
authors.lastname: Ma
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhang
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.forename: Caroline A
authors.initials: CA
authors.lastname: Larregieu
authors.forename: Na
authors.initials: N
authors.lastname: Zhang
authors.forename: Ting
authors.initials: T
authors.lastname: Chu
authors.forename: Hui
authors.initials: H
authors.lastname: Jin
authors.forename: Sheng-Jun
authors.initials: SJ
authors.lastname: Mao
mesh_terms: D000081248:Allylbenzene Derivatives; D000818:Animals; D000840:Anisoles / Q000008:administration & dosage* / Q000737:chemistry; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000737:chemistry; D001249:Asthma / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002452:Cell Count; D004342:Drug Hypersensitivity / Q000209:etiology; D004355:Drug Stability; D004423:Ear / Q000098:blood supply; D004655:Emulsions; D005260:Female; D006168:Guinea Pigs; D007275:Injections, Intravenous; D054709:Lecithins / Q000737:chemistry*; D008297:Male; D051379:Mice; D011092:Polyethylene Glycols / Q000737:chemistry*; D011409:Propylene Glycols / Q000737:chemistry*; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D013024:Soybean Oil / Q000737:chemistry*; D023382:Toxicity Tests, Acute; D014680:Veins / Q000187:drug effects / Q000473:pathology
chemical_list: D000081248:Allylbenzene Derivatives; D000840:Anisoles; D000893:Anti-Inflammatory Agents; D004655:Emulsions; D054709:Lecithins; C116176:PEO-PPO-PEO; D011409:Propylene Glycols; C012195:asarone; D011092:Polyethylene Glycols; D013024:Soybean Oil