title: Application of the central composite design to optimize the preparation of novel micelles of harmine.
abstract: Lactose-palmitoyl-trimethyl-chitosan (Lac-TPCS), a novel amphipathic self-assembled polymer, was synthesized for administration of insoluble drugs to reduce their adverse effects. The central composite design was used to study the preparation technique of harmine (HM)-loaded self-assembled micelles based on Lac-TPCS (Lac-TPCS/HM). Three preparation methods and single factors were screened, including solvent type, HM amount, hydration volume, and temperature. The optimal preparation technique was identified after investigating the influence of two independent factors, namely, HM amount and hydration volume, on four indexes, ie, encapsulation efficiency (EE), drug-loading amount (LD), particle size, and polydispersity index (PDI). Analysis of variance showed a high coefficient of determination of 0.916 to 0.994, thus ensuring a satisfactory adjustment of the predicted prescription. The maximum predicted values of the optimal prescription were 91.62%, 14.20%, 183.3 nm, and 0.214 for EE, LD, size, and PDI, respectively, when HM amount was 1.8 mg and hydration volume was 9.6 mL. HM-loaded micelles were successfully characterized by Fourier-transform infrared spectroscopy, differential scanning calorimetry, X-ray diffraction, and a fluorescence-quenching experiment. Sustained release of Lac-TPCS/HM reached 65.3% in 72 hours at pH 7.4, while free HM released about 99.7% under the same conditions.
authors.affiliation: Department of Pharmaceutics, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, People's Republic of China.
authors.forename: Yong-Yan
authors.initials: YY
authors.lastname: Bei
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Zhou
authors.forename: Ben-Gang
authors.initials: BG
authors.lastname: You
authors.forename: Zhi-Qiang
authors.initials: ZQ
authors.lastname: Yuan
authors.forename: Wei-Liang
authors.initials: WL
authors.lastname: Chen
authors.forename: Peng
authors.initials: P
authors.lastname: Xia
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.forename: Yong
authors.initials: Y
authors.lastname: Jin
authors.forename: Xiao-Juan
authors.initials: XJ
authors.lastname: Hu
authors.forename: Qiao-Ling
authors.initials: QL
authors.lastname: Zhu
authors.forename: Chun-Ge
authors.initials: CG
authors.lastname: Zhang
authors.forename: Xue-Nong
authors.initials: XN
authors.lastname: Zhang
authors.forename: Liang
authors.initials: L
authors.lastname: Zhang
mesh_terms: D002152:Calorimetry, Differential Scanning; D048271:Chitosan / Q000737:chemistry; D006247:Harmine / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D007785:Lactose; D008823:Micelles; D015233:Models, Statistical; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D015203:Reproducibility of Results; D012107:Research Design; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D008823:Micelles; D006247:Harmine; D048271:Chitosan; D007785:Lactose
keywords: central composite design; characterization; chitosan derivate; harmine; response surface methodology; self-assembled micelle