Back to Journals » International Journal of Nanomedicine » Volume 8 » Issue 1

Application of the central composite design to optimize the preparation of novel micelles of harmine

Authors Bei Y, Zhou X, You B, Yuan Z, Chen W, Xia P, Liu Y, Jin Y, Hu X, Zhu Q, Zhang C, Zhang X, Zhang L

Received 1 February 2013

Accepted for publication 22 February 2013

Published 6 May 2013 Volume 2013:8(1) Pages 1795—1808


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Yong-Yan Bei,1,* Xiao-Feng Zhou,2,3,* Ben-Gang You,1 Zhi-Qiang Yuan,1 Wei-Liang Chen,1 Peng Xia,1 Yang Liu,1 Yong Jin,4 Xiao-Juan Hu,1 Qiao-Ling Zhu,1 Chun-Ge Zhang,1 Xue-Nong Zhang,1 Liang Zhang5

1Department of Pharmaceutics, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, People’s Republic of China; 2College of Radiological Medicine and Protection, Soochow University, Suzhou, People’s Republic of China; 3Changshu Hospital of Traditional Chinese Medicine, Changshu, People’s Republic of China; 4Invasive Technology Department, The Second Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 5Department of Biopharmaceutics, College of Pharmaceutical Sciences, Soochow University, Suzhou, People’s Republic of China
*These authors contributed equally to the paper

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.

Keywords: harmine, chitosan derivate, self-assembled micelle, central composite design, response surface methodology, characterization

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]


Other articles by this author:

Stepwise pH-responsive nanoparticles for enhanced cellular uptake and on-demand intracellular release of doxorubicin

Chen WL, Li F, Tang Y, Yang SD, Li JZ, Yuan ZQ, Liu Y, Zhou XF, Liu C, Zhang XN

International Journal of Nanomedicine 2017, 12:4241-4256

Published Date: 6 June 2017

Low-density lipoprotein-coupled micelles with reduction and pH dual sensitivity for intelligent co-delivery of paclitaxel and siRNA to breast tumor

Zhu WJ, Yang SD, Qu CX, Zhu QL, Chen WL, Li F, Yuan ZQ, Liu Y, You BG, Zhang XN

International Journal of Nanomedicine 2017, 12:3375-3393

Published Date: 26 April 2017

Liposomes coated with N-trimethyl chitosan to improve the absorption of harmine in vivo and in vitro

Chen WL, Yuan ZQ, Liu Y, Yang SD, Zhang CG, Li JZ, Zhu WJ, Li F, Zhou XF, Lin YM, Zhang XN

International Journal of Nanomedicine 2016, 11:325-336

Published Date: 19 January 2016

N-Succinyl-chitosan nanoparticles coupled with low-density lipoprotein for targeted osthole-loaded delivery to low-density lipoprotein receptor-rich tumors

Zhang CG, Zhu QL, Zhou Y, Liu Y, Chen WL, Yuan ZQ, Yang SD, Zhou XF, Zhu AJ, Zhang XN, Jin Y

International Journal of Nanomedicine 2014, 9:2919-2932

Published Date: 13 June 2014

Synthesis and characterization of low-toxicity N-caprinoyl-N-trimethyl chitosan as self-assembled micelles carriers for osthole

Hu XJ, Liu Y, Zhou XF, Zhu QL, Bei YY, You BG, Zhang CG, Chen WL, Wang ZL, Zhu AJ, Zhang XN, Fan YJ

International Journal of Nanomedicine 2013, 8:3543-3558

Published Date: 20 September 2013

Novel norcantharidin-loaded liver targeting chitosan nanoparticles to enhance intestinal absorption

Bei YY, Chen XY, Liu Y, Xu JY, Wang WJ, Gu ZL, Xing KL, Zhu AJ, Chen WL, Shi LS, Wang Q, Zhang XN, Zhang Q

International Journal of Nanomedicine 2012, 7:1819-1827

Published Date: 3 April 2012

Pharmacokinetics, tissue distribution, and metabolites of a polyvinylpyrrolidone-coated norcantharidin chitosan nanoparticle formulation in rats and mice, using LC-MS/MS

Ding XY, Hong CJ, Liu Y, Gu ZL, Xing KL, Zhu AJ, Chen WL, Shi LS, Zhang XN, Zhang Q

International Journal of Nanomedicine 2012, 7:1723-1735

Published Date: 2 April 2012

Readers of this article also read:

Patient preference and ease of use for different coagulation factor VIII reconstitution device scenarios: a cross-sectional survey in five European countries

Cimino E, Linari S, Malerba M, Halimeh S, Biondo F, Westfeld M

Patient Preference and Adherence 2014, 8:1713-1720

Published Date: 12 December 2014

Nanostructured systems containing babassu (Orbignya speciosa) oil as a potential alternative therapy for benign prostatic hyperplasia

de Sousa VP, Crean J, Borges VRA, Rodrigues CR, Tajber L, Boylan F, Cabral LM

International Journal of Nanomedicine 2013, 8:3129-3139

Published Date: 15 August 2013

Paclitaxel-loaded poly(glycolide-co-ε-caprolactone)-b-D-α-tocopheryl polyethylene glycol 2000 succinate nanoparticles for lung cancer therapy

Zhao TJ, Chen HZ, Dong YC, Zhang JJ, Huang HD, Zhu J, Zhang W

International Journal of Nanomedicine 2013, 8:1947-1957

Published Date: 16 May 2013

Chitosan-coated boron nitride nanospheres enhance delivery of CpG oligodeoxynucleotides and induction of cytokines

Zhang H, Chen S, Zhi C, Yamazaki T, Hanagata N

International Journal of Nanomedicine 2013, 8:1783-1793

Published Date: 6 May 2013

Complexes containing cationic and anionic pH-sensitive liposomes: comparative study of factors influencing plasmid DNA gene delivery to tumors

Chen Y, Sun J, Lu Y, Tao C, Huang JB, Zhang H, Yu Y, Zou H, Gao J, Zhong YQ

International Journal of Nanomedicine 2013, 8:1573-1593

Published Date: 22 April 2013

Hemostatic absorbable gelatin sponge loaded with 5-fluorouracil for treatment of tumors

Sun W, Chen Y, Yuan W

International Journal of Nanomedicine 2013, 8:1499-1506

Published Date: 18 April 2013

The effects of daily chlorhexidine bathing on cutaneous bacterial isolates: a pilot study

Soma VL, Qin X, Zhou C, Adler A, Berry JE, Zerr DM

Infection and Drug Resistance 2012, 5:75-78

Published Date: 24 April 2012

Novel RGD-lipid conjugate-modified liposomes for enhancing siRNA delivery in human retinal pigment epithelial cells

Chen CW, Lu DW, Yeh MK, Shiau CY, Chiang CH

International Journal of Nanomedicine 2011, 6:2567-2580

Published Date: 26 October 2011

Decline in HAV-associated fulminant hepatic failure and liver transplant in children in Argentina after the introduction of a universal hepatitis A vaccination program

Cervio G, Trentadue J, D´Agostino DE, Luque C, Giorgi MA, Armoni J, Debbag R

Hepatic Medicine: Evidence and Research 2011, 3:99-106

Published Date: 19 September 2011