Pharmaceutical Research

, Volume 23, Issue 8, pp 1877–1887 | Cite as

Screening of Lipid Carriers and Characterization of Drug-Polymer-Lipid Interactions for the Rational Design of Polymer-Lipid Hybrid Nanoparticles (PLN)

  • Yongqiang Li
  • Nicolas Taulier
  • Andrew M. Rauth
  • Xiao Yu Wu
Research Paper


The thermodynamics and solid state properties of components and their interactions in a formulation for polymer-lipid hybrid nanoparticles (PLN) were characterized for screening lead lipid carriers and rational design of PLN.


Verapamil HCl (VRP) was chosen as a model drug and dextran sulfate sodium (DS) as a counter-ionic polymer. Solubility parameters of VRP, VRP-DS complex, and various lipids were calculated and partition of VRP and VRP-DS in lipids was determined. Thermodynamics of VRP binding to DS was determined by isothermal titration calorimetry (ITC). The solid state properties of individual components and their interactions were characterized using differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD).


Dodecanoic acid (DA) was identified as the best lipid carrier among all lipids tested based on the solubility parameters and partition coefficients. VRP-DS complexation was a thermodynamically favorable process. Maximum binding capacity of DS and the highest drug loading capacity of DA were obtained at an equal ionic molar ratio of DS to VRP. In the PLN formulation, DA remained its crystal structure but had a slightly lower melting point, while VRP-DS complex was in an amorphous form.


Drug loading efficiency and capacity of a lipid matrix depend on the VRP-DS binding and the interactions of the complex with the lipid. A combined analysis of solubility parameters and partition coefficients is useful for screening lipid candidates for PLN preparation.

Key words

drug-polymer complex isothermal titration calorimetry partition coefficient polymer-lipid hybrid nanoparticles (PLN) solid lipid nanoparticles solubility parameters 



dodecanoic acid


distilled and deionized


dextran sulfate sodium salt


differential scanning calorimetry


isothermal titration calorimetry


melting point


polymer-lipid hybrid nanoparticles


powder X-ray diffraction


solid lipid nanoparticles


verapamil HCl

VRP-DS complex

the complex of verapamil HCl and dextran sulfate sodium salt



This work was supported by the Canadian Institute of Health Research. The authors would like to thank Dr. Sr. Petrov, Department of Chemistry, University of Toronto, for his comments on the PXRD patterns; Dr. T.V. Chalikian and Dr. Lakshmi P. Kotra for kind permission on use of ITC and a freeze drier, respectively. In addition, the discussion with Ho-lun Wong about SLN, Jubo Liu about solubility parameters and Ms. Feixue Han for help with ITC data fitting; the kind donations of free samples from Gattefossé Inc. (Canada), and the Ontario Graduate Scholarship in Science and Technology (OGSST) to Y. Li are also gratefully acknowledged.


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Copyright information

© Springer Science + Business Media, Inc. 2006

Authors and Affiliations

  • Yongqiang Li
    • 1
  • Nicolas Taulier
    • 1
  • Andrew M. Rauth
    • 2
  • Xiao Yu Wu
    • 1
  1. 1.Leslie Dan Faculty of PharmacyUniversity of TorontoTorontoCanada
  2. 2.Experimental TherapeuticsOntario Cancer InstituteTorontoCanada

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