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Size and charge characterization of polymeric drug delivery systems by Taylor dispersion analysis and capillary electrophoresis

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Abstract

In this work, Taylor dispersion analysis and capillary electrophoresis were used to characterize the size and charge of polymeric drug delivery nanogels based on polyglutamate chains grafted with hydrophobic groups of vitamin E. The hydrophobic vitamin E groups self-associate in water to form small hydrophobic nanodomains that can incorporate small drugs or therapeutic proteins. Taylor dispersion analysis is well suited to determine the weight average hydrodynamic radius of nanomaterials and to get information on the size polydispersity of polymeric samples. The effective charge was determined either from electrophoretic mobility and hydrodynamic radius using electrophoretic modeling (three different approaches were compared), or by indirect UV detection in capillary electrophoresis. The influence of vitamin E hydrophobicity on the polymer effective charge has been studied. The presence of vitamin E leads to a drastic decrease in polymer effective charge in comparison to non-modified polyglutamate. Finally, the electrophoretic behavior of polyglutamate backbone grafted with hydrophobic vitamin E (pGVE) nanogels according to the ionic strength was investigated using the recently proposed slope plot approach. It was deduced that the pGVE nanogels behave electrophoretically as polyelectrolytes which is in good agreement with the high water content of the nanogels.

Size and charge characterization of polyglutamate-based drug delivery systems by Taylor dispersion analysis, indirect UV detection and the 'Slope-plot' approach

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References

  1. Duncan R (2003) The dawning era of polymer therapeutics. Nat Rev Drug Discov 2(5):347–360

    Article  CAS  Google Scholar 

  2. Duncan R, Ringsdorf H, Satchi-Fainaro R (2006) Polymer therapeutics: polymers as drugs, drug and protein conjugates and gene delivery systems: past, present and future opportunities. Adv Polym Sci 192:1–8. doi:10.1007/12_037

    Article  CAS  Google Scholar 

  3. Jeong B, Bae YH, Kim SW (2000) Drug release from biodegradable injectable thermosensitive hydrogel of PEG-PLGA-PEG triblock copolymers. J Controlled Release 63:155–163

    Article  CAS  Google Scholar 

  4. Aurand ER, Lampe KJ, Bjugstad KB (2012) Defining and designing polymers and hydrogels for neural tissue engineering. Neurosci Res 72(3):199–213

    Article  CAS  Google Scholar 

  5. Liechty WB, Kryscio DR, Slaughter BV, Peppas NA (2010) Polymers for drug delivery systems. Annu Rev Chem Biomol Eng 1:149–173

    Article  CAS  Google Scholar 

  6. Allen TM, Cullis PR (2004) Drug delivery systems: entering the mainstream. Science 303(5665):1818–1822

    Article  CAS  Google Scholar 

  7. Liechty WB, Peppas NA (2012) Expert opinion: responsive polymer nanoparticles in cancer therapy. Eur J Pharm Biopharm 80(2):241–246

    Article  CAS  Google Scholar 

  8. Couvreur P, Dubernet C, Puisieux F (1995) controlled drug-delivery with nanoparticles—current possibilities and future trends. Eur J Pharm Biopharm 41(1):2–13

    CAS  Google Scholar 

  9. Brannon-Peppas L, Blanchette JO (2004) Nanoparticle and targeted systems for cancer therapy. Adv Drug Deliv Rev 56(11):1649–1659

    Article  CAS  Google Scholar 

  10. Jewell CM, Zhang J, Fredin NJ, Lynn DM (2005) Multilayered polyelectrolyte films promote the direct and localized delivery of DNA to cells. J Controlled Release 106:214–223

    Article  CAS  Google Scholar 

  11. Raemdonck K, Demeester J, De Smedt S (2009) Advanced nanogel engineering for drug delivery. Soft Matter 5(4):707–715

    Article  CAS  Google Scholar 

  12. Peppas NA, Bures P, Leobandung W, Ichikawa H (2000) Hydrogels in pharmaceutical formulations. Eur J Pharm Biopharm 50(1):27–46

    Article  CAS  Google Scholar 

  13. Lin C-C, Anseth K (2009) PEG hydrogels for the controlled release of biomolecules in regenerative medicine. Pharm Res 26(3):631–643

    Article  CAS  Google Scholar 

  14. Fisher O, Kim T, Dietz S, Peppas N (2009) Enhanced core hydrophobicity, functionalization and cell penetration of polybasic nanomatrices. Pharm Res 26(1):51–60

    Article  CAS  Google Scholar 

  15. Kafka AP, Kleffmann T, Rades T, McDowell A (2009) Histidine residues in the peptide D-Lys(6)-GnRH: potential for copolymerization in polymeric nanoparticles. Mol Pharm 6(5):1483–1491

    Article  CAS  Google Scholar 

  16. Sahiner N, Ilgin P (2010) Synthesis and characterization of soft polymeric nanoparticles and composites with tunable properties. J Polym Sci Pol Chem 48(22):5239–5246

    Article  CAS  Google Scholar 

  17. Chan YP, Meyrueix R, Kravtzoff R, Nicolas F, Lundstrom K (2007) Review on Medusa (R): a polymer-based sustained release technology for protein and peptide drugs. Expert Opin Drug Deliv 4(4):441–451

    Article  CAS  Google Scholar 

  18. Sharma U, Gleason NJ, Carbeck JD (2005) Diffusivity of solutes measured in glass capillaries using Taylor’s analysis of dispersion and a commercial CE instrument. Anal Chem 77(3):806–813

    Article  CAS  Google Scholar 

  19. Ye F, Jensen H, Larsen SW, Yaghmur A, Larsen C, Ostergaard J (2012) Measurement of drug diffusivities in pharmaceutical solvents using Taylor dispersion analysis. J Pharm Biomed Anal 61:176–183

    Article  CAS  Google Scholar 

  20. Cottet H, Biron JP, Cipelletti L, Matmour R, Martin M (2010) Determination of individual diffusion coefficients in evolving binary mixtures by Taylor dispersion analysis: application to the monitoring of polymer reaction. Anal Chem 82(5):1793–1802

    Article  CAS  Google Scholar 

  21. Le Saux T, Cottet H (2008) Size-based characterization by the coupling of capillary electrophoresis to Taylor dispersion analysis. Anal Chem 80(5):1829–1832

    Article  Google Scholar 

  22. Leclercq L, Cottet H (2012) Fast characterization of polyelectrolyte complexes by inline coupling of capillary electrophoresis to Taylor dispersion analysis. Anal Chem 84(3):1740–1743

    Article  CAS  Google Scholar 

  23. d’Orlye F, Varenne A, Gareil P (2008) Determination of nanoparticle diffusion coefficients by Taylor dispersion analysis using a capillary electrophoresis instrument. J Chromatogr A 1204(2):226–232

    Article  Google Scholar 

  24. Cottet H, Martin M, Papillaud A, Souaid E, Collet H, Commeyras A (2007) Determination of dendrigraft poly-L-lysine diffusion coefficients by Taylor dispersion analysis. Biomacromolecules 8(10):3235–3243

    Article  CAS  Google Scholar 

  25. Hawe A, Hulse WL, Jiskoot W, Forbes RT (2011) Taylor dispersion analysis compared to dynamic light scattering for the size analysis of therapeutic peptides and proteins and their aggregates. Pharm Res 28(9):2302–2310

    Article  CAS  Google Scholar 

  26. Ostergaard J, Jensen H (2009) Simultaneous evaluation of ligand binding properties and protein size by electrophoresis and Taylor dispersion in capillaries. Anal Chem 81(20):8644–8648

    Article  Google Scholar 

  27. Hulse WL, Forbes RT (2011) A nanolitre method to determine the hydrodynamic radius of proteins and small molecules by Taylor dispersion analysis. Int J Pharm 411(1–2):64–68

    Article  CAS  Google Scholar 

  28. Hulse W, Forbes R (2011) A Taylor dispersion analysis method for the sizing of therapeutic proteins and their aggregates using nanolitre sample quantities. Int J Pharm 416(1):394–397

    Article  CAS  Google Scholar 

  29. Franzen U, Vermehren C, Jensen H, Ostergaard J (2011) Physicochemical characterization of a PEGylated liposomal drug formulation using capillary electrophoresis. Electrophoresis 32(6–7):738–748

    Article  CAS  Google Scholar 

  30. Bello MS, Rezzonico R, Righetti PG (1994) Use of taylor-aris dispersion for measurement of a solute diffusion-coefficient in thin capillaries. Science 266(5186):773–776

    Article  CAS  Google Scholar 

  31. Cottet H, Biron JP, Martin M (2007) Taylor dispersion analysis of mixtures. Anal Chem 79(23):9066–9073

    Article  CAS  Google Scholar 

  32. Gitlin I, Carbeck JD, Whitesides GM (2006) Why are proteins charged? Networks of charge-charge interactions in proteins measured by charge ladders and capillary electrophoresis. Angew Chem Int Ed 45(19):3022–3060

    Article  CAS  Google Scholar 

  33. Seyrek E, Dubin PL, Henriksen J (2007) Nonspecific electrostatic binding characteristics of the heparin-antithrombin interaction. Biopolymers 86(3):249–259

    Article  CAS  Google Scholar 

  34. Manning GS (1969) Limiting laws and counterion condensation in polyelectrolyte solutions. I. Colligative properties. J Chem Phys 51(3):924–933

    Article  CAS  Google Scholar 

  35. Chepelianskii A, Mohammad-Rafiee F, Trizac E, Raphael E (2009) On the effective charge of hydrophobic polyelectrolytes. J Phys Chem B 113(12):3743–3749

    Article  CAS  Google Scholar 

  36. Essafi W, Lafuma F, Baigl D, Williams CE (2005) Anomalous counterion condensation in salt-free hydrophobic polyelectrolyte solutions: osmotic pressure measurements. Europhys Lett 71(6):938–944

    Article  CAS  Google Scholar 

  37. Allison SA, Perrin C, Cottet H (2011) Modeling the electrophoresis of oligolysines. Electrophoresis 32(20):2788–2796

    Article  CAS  Google Scholar 

  38. Vuletic T, Babic SD, Grgicin D, Aumiler D, Radler J, Livolant F, Tomic S (2011) Manning free counterion fraction for a rodlike polyion: aqueous solutions of short DNA fragments in presence of very low added salt. Physical Review E 83(4):8–16

    Article  Google Scholar 

  39. Boisvert JP, Malgat A, Pochard I, Daneault C (2002) Influence of the counter-ion on the effective charge of polyacrylic acid in dilute condition. Polymer 43(1):141–148

    Article  CAS  Google Scholar 

  40. Combet J, Rawiso M, Rochas C, Hoffmann S, Boue F (2011) Structure of polyelectrolytes with mixed monovalent and divalent counterions: SAXS measurements and Poisson–Boltzmann analysis. Macromolecules 44(8):3039–3052

    Article  CAS  Google Scholar 

  41. Bohme U, Scheler U (2003) Effective charge of poly(styrenesulfonate) and ionic strength—an electrophoresis NMR investigation. Colloids Surf A 222(1–3):35–40

    Article  CAS  Google Scholar 

  42. Anik N, Airiau M, Labeau MP, Vuong CT, Reboul J, Lacroix-Desmazes P, Gerardin C, Cottet H (2009) Determination of polymer effective charge by indirect UV detection in capillary electrophoresis: toward the characterization of macromolecular architectures. Macromolecules 42(7):2767–2774

    Article  CAS  Google Scholar 

  43. Pyell U, Bucking W, Huhn C, Herrmann B, Merkoulov A, Mannhardt J, Jungclas H, Nann T (2009) Calibration-free concentration determination of charged colloidal nanoparticles and determination of effective charges by capillary isotachophoresis. Anal Bioanal Chem 395(6):1681–1691

    Article  CAS  Google Scholar 

  44. Agnihotri SM, Ohshima H, Terada H, Tomoda K, Makino K (2009) Electrophoretic mobility of colloidal gold particles in electrolyte solutions. Langmuir 25(8):4804–4807

    Article  CAS  Google Scholar 

  45. Oukacine F, Morel A, Cottet H (2011) Characterization of carboxylated nanolatexes by capillary electrophoresis. Langmuir 27(7):4040–4047

    Article  CAS  Google Scholar 

  46. Xin Y, Mitchell H, Cameron H, Allison SA (2006) Modeling the electrophoretic mobility and diffusion of weakly charged peptides. J Phys Chem B 110(2):1038–1045

    Article  CAS  Google Scholar 

  47. Li SK, Liddell MR, Wen H (2011) Effective electrophoretic mobilities and charges of anti-VEGF proteins determined by capillary zone electrophoresis. J Pharm Biomed Anal 55(3):603–607

    Article  CAS  Google Scholar 

  48. Ibrahim A, Ohshima H, Allison SA, Cottet H (2012) Determination of effective charge of small ions, polyelectrolytes and nanoparticles by capillary electrophoresis. J Chromatogr A 1247:154–164

    Article  CAS  Google Scholar 

  49. Taylor G (1953) Dispersion of soluble matter in solvent flowing slowly through a tube. Proc R Soc London, Ser A 219(1137):186–203

    Article  CAS  Google Scholar 

  50. Aris R (1956) On the dispersion of a solute in a fluid flowing through a tube. Proc R Soc London, Ser A 235(1200):67–77

    Article  Google Scholar 

  51. Chamieh J, Oukacine F, Cottet H (2012) Taylor dispersion analysis with two detection points on a commercial capillary electrophoresis apparatus. J Chromatogr A 1235:174–177

    Article  CAS  Google Scholar 

  52. Taylor G (1954) Conditions under which dispersion of a solute in a stream of solvent can be used to measure molecular diffusion. Proc R Soc London, Ser A 225(1163):473–477

    Article  CAS  Google Scholar 

  53. Chamieh J, Cottet H (2012) Comparison of single and double detection points Taylor dispersion analysis for monodisperse and polydisperse samples. J Chromatogr A 1241:123–127

    Article  CAS  Google Scholar 

  54. Einstein A (1906) A new determination of the molecular dimensions. Ann Phys 19(2):289–306

    Article  CAS  Google Scholar 

  55. Stokes G (1966) Vol Cambridge Philos Trans 1851;9:8. Reprinted in: Mathematical and Physical Papers, 2nd edition. Johnson Reprint Corp., New York

  56. Pitts E (1953) An extension of the theory of the conductivity and viscosity of electrolyte solutions. Proc R Soc London, Ser A 217(1128):43–70

    Article  CAS  Google Scholar 

  57. Plasson R, Cottet H (2005) Determination of homopolypeptide conformational changes by the modeling of electrophoretic mobilities. Anal Chem 77(18):6047–6054

    Article  CAS  Google Scholar 

  58. Friedl W, Reijenga JC, Kenndler E (1995) Ionic-strength and charge number correction for mobilities of multivalent organic-anions in capillary electrophoresis. J Chromatogr A 709(1):163–170

    Article  CAS  Google Scholar 

  59. Long D et al (1996) A Zimm model for polyelectrolytes in an electric field. J Phys Condens Matter 8(47):9471–9475

    Article  CAS  Google Scholar 

  60. Ohshima H (2001) Approximate analytic expression for the electrophoretic mobility of a spherical colloidal particle. J Colloid Interface Sci 239(2):587–590

    Article  CAS  Google Scholar 

  61. Makino K, Ohshima H (2010) Electrophoretic mobility of a colloidal particle with constant surface charge density. Langmuir 26(23):18016–18019

    Article  CAS  Google Scholar 

  62. Yoon BJ, Kim S (1989) Electrophoresis of spheroidal particles. J Colloid Interface Sci 128(1):275–288

    Article  CAS  Google Scholar 

  63. Allison SA, Pei HX, Baek S, Brown J, Lee MY, Nguyen V, Twahir UT, Wu HF (2010) The dependence of the electrophoretic mobility of small organic ions on ionic strength and complex formation. Electrophoresis 31(5):920–932

    Article  CAS  Google Scholar 

  64. Ohshima H (1994) A simple expression for henrys function for the retardation effect in electrophoresis of spherical colloidal particles. J Colloid Interface Sci 168(1):269–271

    Article  CAS  Google Scholar 

  65. O’Brien RW, White LR (1978) Electrophoretic mobility of a spherical colloidal particle. J Chem Soc Faraday Trans 2(74):1607–1626

    Google Scholar 

  66. Doble P, Andersson P, Haddad PR (1997) Determination and prediction of transfer ratios for anions in capillary zone electrophoresis with indirect UV detection. J Chromatogr A 770(1–2):291–300

    CAS  Google Scholar 

  67. Hjerten S, Elenbring K, Kilar F, Liao JL, Chen AJC, Siebert CJ, Zhu MD (1987) Carrier-free zone electrophoresis, displacement electrophoresis and isoelectric-focusing in a high-performance electrophoresis apparatus. J Chromatogr 403:47–61

    Article  CAS  Google Scholar 

  68. Johns C, Macka M, Haddad PR (2003) Enhancement of detection sensitivity for indirect photometric detection of anions and cations in capillary electrophoresis. Electrophoresis 24(12–13):2150–2167

    Article  CAS  Google Scholar 

  69. Kohlrausch F (1897) Ueber Concentrations-Verschiebungen durch Electrolyse im Inneren von Lösungen und Lösungsgemischen. Ann Phys 298(10):209–239

    Article  Google Scholar 

  70. Nishio T (1998) Monte Carlo studies on potentiometric titration of poly(glutamic acid). Biophys Chem 71(2–3):173–184

    Article  CAS  Google Scholar 

  71. Holm C, Joanny JF, Kremer K, Netz RR, Reineker P, Seidel C, Vilgis TA, Winkler RG (2004) Polyelectrolyte theory. In: Schmidt M (ed) Polyelectrolytes with defined molecular architecture. Springer, Berlin, pp 67–111

    Chapter  Google Scholar 

  72. Ibrahim A, Allison SA, Cottet H (2012) Extracting information from the ionic strength dependence of electrophoretic mobility by use of the slope plot. Anal Chem 84:9422–9430

    CAS  Google Scholar 

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Acknowledgments

H.C. gratefully acknowledges the support from the Région Languedoc-Roussillon for the fellowship “Chercheurs d’Avenir” and from the Institut Universitaire de France.

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Authors and Affiliations

  1. Institut des Biomolécules Max Mousseron (UMR 5247 CNRS-Université de Montpellier 1-Université de Montpellier 2), place Eugène Bataillon CC 1706, 34095, Montpellier Cedex 5, France

    Amal Ibrahim & Hervé Cottet

  2. Flamel Technologies, Parc Club du Moulin à Vent, 33, avenue du Dr Georges Lévy, 69693, Vénissieux, France

    Rémi Meyrueix, Gauthier Pouliquen & You Ping Chan

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  1. Amal Ibrahim
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  2. Rémi Meyrueix
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Correspondence to Hervé Cottet.

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Ibrahim, A., Meyrueix, R., Pouliquen, G. et al. Size and charge characterization of polymeric drug delivery systems by Taylor dispersion analysis and capillary electrophoresis. Anal Bioanal Chem 405, 5369–5379 (2013). https://doi.org/10.1007/s00216-013-6972-4

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