Abstract
Interactions of drug candidates with the biomacromolecules of the synovial fluid affect drug targeting to the articular cartilage as well as clearance from the synovial space upon intra-articular administration. Hyaluronic acid (HA) and human serum albumin (HSA) are two main components existing in the synovial fluid. To this end, we investigated the affinity of seven cationic amino acid and dipeptide β-naphthylamide derivatives towards HA and HSA in order to shed light on possible relationships between physicochemical properties, in particular charge state, and biomacromolecular interactions to increase the joint residence time. Capillary electrophoresis frontal analysis was used for characterization of the binding of the derivatives to hyaluronic acid and HSA at 25 °C in acetate buffer (pH 4.65) and phosphate buffer (pH 7.40), respectively. Linear binding isotherms were observed for the ligand–hyaluronic acid interactions and the obtained binding constants ranged from 43 to 133 M−1. The average fraction of bound ligand towards hyaluronic acid increased with increasing the net charge of the ligands but was less than 67 % for all investigated ligands. The obtained binding constants of the ligands with HSA varied in the range of 103–106 M−1. The interactions of low-molecular weight derivatives with hyaluronic acid were highly dependent on the ligand charge state. This trend was not observed for the interactions with HSA. The obtained affinity data may provide useful information in the design of cartilage adhesive prodrugs with extended residence time in the synovial cavity.
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Larsen C, Østergaard J, Larsen SW, Jensen H, Jacobsen S, Lindegaard C, Andersen PH (2008) Intra-articular depot formulation principles: role in the management of postoperative pain and arthritic disorders. J Pharm Sci 97:4622–4654
Owen SG, Francis HW, Roberts MS (1994) Disappearance kinetics of solutes from synovial fluid after intra-articular injection. Br J Clin Pharmacol 38:349–355
Gerwin N, Hops C, Lucke A (2006) Intraarticular drug delivery in osteoarthritis. Adv Drug Deliv Rev 58:226–242
McLendon PM, Buckwalter DJ, Davis EM, Reineke TM (2010) Interaction of poly(glycoamidoamine) DNA delivery vehicles with cell-surface glycosaminoglycans leads to polyplex internalization in a manner not solely dependent on charge. Mol Pharmaceutics 7:1757–1768
Liao YH, Jones SA, Forbes B, Martin GP, Brown MB (2005) Hyaluronan: pharmaceutical characterization and drug delivery. Drug Delivery 12:327–342
Van Vlierberghe S, Dubruel P, Schacht E (2011) Biopolymer-based hydrogels as scaffolds for tissue engineering applications: a review. Biomacromolecules 12:1387–1408
Santos HA, Manzanares JA, Murtomaki L, Kontturi K (2007) Thermodynamic analysis of binding between drugs and glycosaminoglycans by isothermal titration calorimetry and fluorescence spectroscopy. Eur J Pharm Sci 32:105–114
Hernaiz MJ, Lebrun LA, Wu Y, Sen JW, Linhardt RJ, Heegaard NHH (2002) Characterization of heparin binding by a peptide from amyloid P component using capillary electrophoresis, surface plasmon resonance and isothermal titration calorimetry. Eur J Biochem 269:2860–2867
Ehtezazi T, Govender T, Stolnik S (2000) Hydrogen bonding and electrostatic interaction contributions to the interaction of a cationic drug with polyaspartic acid. Pharm Res 17:871–877
Mrestani Y, Hammitzch M, Neubert RHH (2009) Investigation of the interaction between lidocaine and the components of hyaluronic acid using frontal analysis continuous capillary electrophoresis. Chromatographia 69:1321–1324
Østergaard J, Khanbolouki A, Jensen H, Larsen C (2004) Complexation between low-molecular-weight cationic ligands and negatively charges polymers as studied by capillary electrophoresis frontal analysis. Electrophoresis 25:3168–3175
Østergaard J, Jensen H, Larsen SW, Larsen C (2009) Binding of low-molecular-weight cationic ligands to chondroitin sulfate as studied by capillary electrophoresis frontal analysis. Open Anal Chem J 3:16–31
Vuignier K, Schappler J, Veuthey JL, Carrupt PA, Martel S (2010) Drug-protein binding: a critical review of analytical tools. Anal Bioanal Chem 398:53–66
Østergaard J, Heegaard NHH (2003) Capillary electrophoresis frontal analysis: principles and applications for the study of drug–plasma protein binding. Electrophoresis 24:2903–2913
Østergaard J, Heegaard NHH (2006) Bioanalytical interaction studies executed by preincubation affinity capillary electrophoresis. Electrophoresis 27:2590–2608
Oravcova J, Bohs B, Lindner W (1996) Drug-protein binding studies—new trends in analytical and experimental methodology. J Chromatogr B 677:1–28
Neubert RHH, Rüttinger H-H (2003) Affinity capillary electrophoresis in pharmaceutics and biopharmaceutics. Marcel Dekker, New York
Zou T, Oukacine F, Le Saux T, Cottet H (2010) Neutral coatings for the study of polycation/multicharged anion interactions by capillary electrophoresis: application to dendrigraft poly-l-lysines with negatively multicharged molecules. Anal Chem 82:7362–7368
Busch MHA, Carels LB, Boelens HFM, Kraak JC, Poppe H (1997) Comparison of five methods for the study of drug-protein binding in affinity capillary electrophoresis. J Chromatogr A 777:311–328
Heegaard NHH, Nilsson S, Guzman NA (1998) Affinity capillary electrophoresis: important application areas and some recent developments. J Chromatogr B 715:29–54
Rundlett KL, Armstrong DW (2001) Methods for the determination of binding constants by capillary electrophoresis. Electrophoresis 22:1419–1427
Ishihama Y, Miwa T, Asakawa N (2002) Drug–plasma protein binding assay by electrokinetic chromatography-frontal analysis. Electrophoresis 23:951–955
Knjazeva T, Kaljurand M (2010) Capillary electrophoresis frontal analysis for the study of flavonoid interactions with human serum albumin. Anal Bioanal Chem 397:2211–2219
Liu C, Kang J (2012) Improved capillary electrophoresis frontal analysis by dynamically coating the capillary with polyelectrolyte multilayers. J Chromatogr A 1238:146–151
Vuignier K, Schappler J, Veuthey JL, Carrupt PA, Martel S (2010) Improvement of a capillary electrophoresis/frontal analysis (CE/FA) method for determining binding constants: discussion on relevant parameters. J Pharm Biomed Anal 53:1288–1297
Jensen H, Østergaard J, Thomsen AE, Hansen SH (2007) CE frontal analysis based on simultaneous UV and contactless conductivity detection: a general setup for studying noncovalent interactions. Electrophoresis 28:322–327
Seyrek E, Dubin PL, Tribet C, Gamble EA (2003) Ionic strength dependence of protein–polyelectrolyte interactions. Biomacromolecules 4:273–282
Gao JY, Dubin PL, Muhoberac BB (1997) Measurement of the binding of proteins to polyelectrolytes by frontal analysis continuous capillary electrophoresis. Anal Chem 69:2945–2951
Hattori T, Bat-Aldar S, Kato R, Bohidar HB, Dubin PL (2005) Characterization of polyanion-protein complexes by frontal analysis continuous capillary electrophoresis and small angle neutron scattering: effect of polyanion flexibility. Anal Biochem 342:229–236
Porcar I, Cottet H, Gareil P, Tribet C (1999) Association between protein particles and long amphiphilic polymers: effect of the polymer hydrophobicity on binding isotherms. Macromolecules 32:3922–3929
Girardot M, Li HY, Descroix S, Varenne A (2011) Determination of binding parameters between lysozyme and its aptamer by frontal analysis continuous microchip electrophoresis (FACMCE). J Chromatogr A 1218:4052–4058
Nicolas C, Verny M, Giraud I, Ollier M, Rapp M, Maurizis JC, Madelmont JC (1999) New quaternary ammonium oxicam derivatives targeted toward cartilage: synthesis, pharmacokinetic studies, and antiinflammatory potency. J Med Chem 42:5235–5240
Giraud I, Rapp M, Maurizis JC, Madelmont JC (2000) Application to a cartilage targeting strategy: synthesis and in vivo biodistribution of C14-labeled quaternary ammonium glucosamine conjugates. Bioconjugate Chem 11:212–218
Peters T Jr (1996) All about albumin: biochemistry, genetics, and medical applications. Academic Press, Dan Diego
Klotz IM (1997) Ligand-receptor energetics. A guide for the perplexed. Wiley, New York
Mcghee JD, Hippel PHV (1974) Theoretical aspects of DNA–protein interactions—cooperative and non-cooperative binding of large ligands to a one-dimensional homogeneous lattice. J Mol Biol 86:469–489
Gonciarz A, Kus K, Szafarz M, Walczak M, Zakrzewska A, Szymura-Oleksiak J (2012) Capillary electrophoresis/frontal analysis versus equilibrium dialysis in dexamethasone sodium phosphate–serum albumin binding studies. Electrophoresis 33:3323–3330
Liu X, Chen X, Yue Y, Zhang J, Song Y (2008) Study of interaction between drug enantiomers and human serum albumin by flow injection-capillary electrophoresis frontal analysis. Electrophoresis 29:2876–2883
Ohnishi T, Mohamed NAL, Shibukawa A, Kuroda Y, Nakagawa T, El Gizawy S, Askal HF, El Kommos ME (2002) Frontal analysis of drug-plasma lipoprotein binding using capillary electrophoresis. J Pharm Biomed Anal 27:607–614
Zia V, Rajewski RA, Stella VJ (2001) Effect of cyclodextrin charge on complexation of neutral and charged substrates: comparison of (SBE)7M-beta-CD to HP-beta-CD. Pharm Res 18:667–673
Fuoss RM (1958) Ionic association III. The equilibrium between ion pairs and free ions. J Am Chem Soc 80:5059–5061
Rehm D, Weller A (1969) Kinetik und mechanismus der elektronübertragung bei der fluoreszenzlöschung in acetonitril. Ber Bunsenges Physik Chem 73:834–839
Cajori FA, Pemberton R (1928) The chemical composition of synovial fluid in cases of joint effusion. J Biol Chem 76:471–480
Østergaard J, Schou C, Larsen C, Heegaard NHH (2002) Evaluation of capillary electrophoresis-frontal analysis for the study of low molecular weight drug–human serum albumin interactions. Electrophoresis 23:2842–2853
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These studies were supported by The Danish Medical Research Council.
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Ye, F., Xie, Y., Jensen, H. et al. Interaction of Amino Acid and Dipeptide β-Naphthylamide Derivatives with Hyaluronic Acid and Human Serum Albumin Studied by Capillary Electrophoresis Frontal Analysis. Chromatographia 76, 49–57 (2013). https://doi.org/10.1007/s10337-012-2369-3
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DOI: https://doi.org/10.1007/s10337-012-2369-3