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

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Purpose

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.

Methods

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).

Results

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.

Conclusions

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.

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Abbreviations

DA:

dodecanoic acid

DDI:

distilled and deionized

DS:

dextran sulfate sodium salt

DSC:

differential scanning calorimetry

ITC:

isothermal titration calorimetry

MP:

melting point

PLN:

polymer-lipid hybrid nanoparticles

PXRD:

powder X-ray diffraction

SLN:

solid lipid nanoparticles

VRP:

verapamil HCl

VRP-DS complex:

the complex of verapamil HCl and dextran sulfate sodium salt

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Acknowledgments

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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Authors and Affiliations

  1. Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, M5S 2S2, Canada

    Yongqiang Li, Nicolas Taulier & Xiao Yu Wu

  2. Experimental Therapeutics, Ontario Cancer Institute, Toronto, ON, M5G 2M9, Canada

    Andrew M. Rauth

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  1. Yongqiang Li
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  2. Nicolas Taulier
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Correspondence to Xiao Yu Wu.

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Li, Y., Taulier, N., Rauth, A.M. et al. Screening of Lipid Carriers and Characterization of Drug-Polymer-Lipid Interactions for the Rational Design of Polymer-Lipid Hybrid Nanoparticles (PLN). Pharm Res 23, 1877–1887 (2006). https://doi.org/10.1007/s11095-006-9033-2

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  • DOI: https://doi.org/10.1007/s11095-006-9033-2

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