title: Systemic delivery of alpha-asarone with Kolliphor HS 15 improves its safety and therapeutic effect on asthma.
abstract: The commercially available alpha-asarone injections (CA-ARE) were frequently found to cause severe anaphylactic reactions by the solubilizer contained in the formulation such as polysorbate 80 and propylene glycol. This study aimed to develop a new ARE injection using Kolliphor HS 15 as solubilizing agent (HS 15-ARE) by the dissolution method to resolve its poor solubility problem and reduce the anaphylaxis of CA-AREs caused by Polysorbate 80. The HS 15-ARE micelle showed a homogeneous round shape with the mean particle size of around 13.73 ± 0.02 nm, polydisperse index (PDI) of 0.19 ± 0.01 and solubilizing efficiency of 95.7% ± 2.4%. In vitro and in vivo studies showed that HS 15-ARE is a stable injection presenting the same pharmacokinetic profile with CA-ARE. Moreover, improved therapeutic effect was observed for HS 15-ARE in treating asthma compared to CA-ARE (p < 0.05) with no anaphylactic reactions observed. These results demonstrate that the new formulation of ARE (HS 15-ARE) has a great potential for replacing CA-AREs injections.
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery, Ministry of Education, Sichuan University , Chengdu , China.
authors.forename: Hua
authors.initials: H
authors.lastname: Lu
authors.forename: Jianbo
authors.initials: J
authors.lastname: Li
authors.forename: Man
authors.initials: M
authors.lastname: Li
authors.forename: Tao
authors.initials: T
authors.lastname: Gong
authors.forename: Zhirong
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D000081248:Allylbenzene Derivatives; D000707:Anaphylaxis / Q000097:blood / Q000139:chemically induced*; D000818:Animals; D000840:Anisoles / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use; D001249:Asthma / Q000097:blood / Q000188:drug therapy*; D001682:Biological Availability; D002478:Cells, Cultured; D002626:Chemistry, Pharmaceutical; D004195:Disease Models, Animal; D004355:Drug Stability; D004912:Erythrocytes / Q000187:drug effects; D006168:Guinea Pigs; D006461:Hemolysis / Q000187:drug effects; D006632:Histamine / Q000097:blood; D007275:Injections, Intravenous; D008297:Male; D015394:Molecular Structure; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry*; D017208:Rats, Wistar; D012756:Sheep; D012997:Solvents / Q000737:chemistry*; D013228:Stearates / Q000737:chemistry*; D013499:Surface Properties; D014018:Tissue Distribution
chemical_list: D000081248:Allylbenzene Derivatives; D000840:Anisoles; D018927:Anti-Asthmatic Agents; C000605765:Kolliphor HS 15; D012997:Solvents; D013228:Stearates; C012195:asarone; D011092:Polyethylene Glycols; D006632:Histamine
keywords: ARE solubilizing efficiency; Alpha-asarone; Kolliphor HS 15; anaphylaxis; asthma; pharmacokinetics; polysorbate 80; tissue distributions