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

A novel drug–phospholipid complex enriched with micelles: preparation and evaluation in vitro and in vivo

Authors Xia H, Zhang Z, Jin X, Hu Q, Chen X, Jia X

Received 24 October 2012

Accepted for publication 28 November 2012

Published 4 February 2013 Volume 2013:8(1) Pages 545—554


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Hai-jian Xia,1,2 Zhen-hai Zhang,1 Xin Jin,1 Qin Hu,1 Xiao-yun Chen,1 Xiao-bin Jia1

1Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Nanjing, China; 2College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China

Abstract: Mixed micelles are widely used to increase solubility and bioavailability of poorly soluble drugs. One promising antitumor drug candidate is 20(S)-protopanaxadiol (PPD), although its clinical application is limited by low water solubility and poor bioavailability after oral administration. In this study, we developed mixed micelles consisting of PPD–phospholipid complexes and Labrasol® and evaluated their potential for oral PPD absorption. Micelles were prepared using a solvent-evaporation method, and their physicochemical properties, including particle size, zeta potential, morphology, crystal type, drug loading, drug entrapment efficiency, and solubility, were characterized. Furthermore, in vitro release was investigated using the dialysis method, and transport and bioavailability of the mixed micelles were investigated through a Caco-2 cell monolayer and in vivo absorption studies performed in rats. Compared with the solubility of free PPD (3 µg/mL), the solubility of PPD in the prepared mixed micelles was 192.41 ± 1.13 µg/mL in water at room temperature. The in vitro release profiles showed a significant difference between the more rapid release of free PPD and the slower and more sustained release of the mixed micelles. At the end of a 4-hour transport study using Caco-2 cells, the apical-to-basolateral apparent permeability coefficients (Papp) increased from (1.12 ± 0.21) × 106 cm/s to (1.78 ± 0.16) × 106 cm/s, while the basolateral-to-apical Papp decreased from (2.42 ± 0.16) × 106 cm/s to (2.12 ± 0.32) × 106. In this pharmacokinetic study, compared with the bioavailability of free PPD (area under the curve [AUC]0–8), the bioavailability of PPD from the micelles (AUC0–8) increased by approximately 216.36%. These results suggest that novel mixed micelles can significantly increase solubility, enhance absorption, and improve bioavailability. Thus, these prepared micelles might be potential carriers for oral PPD delivery in antitumor therapies.

Keywords: 20(S)-protopanaxadiol, phospholipid complex, Labrasol, mixed micelles, Caco-2 cell monolayer, bioavailability

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]


Readers of this article also read:

Diagnostic and therapeutic path of breast cancer: effectiveness, appropriateness, and costs – results from the DOCMa study

Giovagnoli MR, Bonifacino A, Neglia C, Benvenuto M, Sambati FV, Giolli L, Giovagnoli A, Piscitelli P

Clinical Interventions in Aging 2015, 10:741-749

Published Date: 17 April 2015

Tumor targeting and imaging with dual-peptide conjugated multifunctional liposomal nanoparticles

Rangger C, Helbok A, Sosabowski J, Kremser C, Koehler G, Prassl R, Andreae F, Virgolini IJ, von Guggenberg E, Decristoforo C

International Journal of Nanomedicine 2013, 8:4659-4671

Published Date: 5 December 2013

Predictive modeling of nanomaterial exposure effects in biological systems

Liu X, Tang K, Harper S, Harper B, Steevens JA, Xu R

International Journal of Nanomedicine 2013, 8:31-43

Published Date: 16 September 2013

Enhanced transdermal bioavailability of testosterone propionate via surfactant-modified ethosomes

Meng S, Chen Z, Yang L, Zhang W, Liu D, Guo J, Guan Y, Li J

International Journal of Nanomedicine 2013, 8:3051-3060

Published Date: 13 August 2013

Fabrication of small-diameter vascular scaffolds by heparin-bonded P(LLA-CL) composite nanofibers to improve graft patency

Wang S, Mo XM, Jiang BJ, Gao CJ, Wang HS, Zhuang YG, Qiu LJ

International Journal of Nanomedicine 2013, 8:2131-2139

Published Date: 7 June 2013

Acoustic cardiac signals analysis: a Kalman filter–based approach

Salleh SH, Hussain HS, Swee TT, Ting CM, Noor AM, Pipatsart S, Ali J, Yupapin PP

International Journal of Nanomedicine 2012, 7:2873-2881

Published Date: 11 June 2012

Association between calcifying nanoparticles and placental calcification

Guo Y, Zhang D, Lu H, Luo S, Shen X

International Journal of Nanomedicine 2012, 7:1679-1686

Published Date: 27 March 2012


Iancu C, Mocan L

International Journal of Nanomedicine 2011, 6:2543-2544

Published Date: 21 October 2011