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Multiscale Experimental Evaluation of Agarose-Based Semi-Interpenetrating Polymer Network Hydrogels as Materials with Tunable Rheological and Transport Performance

. 2020 Oct 31 ; 12 (11) : . [epub] 20201031

Status PubMed-not-MEDLINE Language English Country Switzerland Media electronic

Document type Journal Article

Grant support
REG LO1211 Ministerstvo Školství, Mládeže a Tělovýchovy
LD15047 Ministerstvo Školství, Mládeže a Tělovýchovy
GA17-15451S Grantová Agentura České Republiky

This study introduces an original concept in the development of hydrogel materials for controlled release of charged organic compounds based on semi-interpenetrating polymer networks composed by an inert gel-forming polymer component and interpenetrating linear polyelectrolyte with specific binding affinity towards the carried active compound. As it is experimentally illustrated on the prototype hydrogels prepared from agarose interpenetrated by poly(styrene sulfonate) (PSS) and alginate (ALG), respectively, the main benefit brought by this concept is represented by the ability to tune the mechanical and transport performance of the material independently via manipulating the relative content of the two structural components. A unique analytical methodology is proposed to provide complex insight into composition-structure-performance relationships in the hydrogel material combining methods of analysis on the macroscopic scale, but also in the specific microcosms of the gel network. Rheological analysis has confirmed that the complex modulus of the gels can be adjusted in a wide range by the gelling component (agarose) with negligible effect of the interpenetrating component (PSS or ALG). On the other hand, the content of PSS as low as 0.01 wt.% of the gel resulted in a more than 10-fold decrease of diffusivity of model-charged organic solute (Rhodamine 6G).

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Ahmed E.M. Hydrogel: Preparation, characterization, and applications: A review. J. Adv. Res. 2015;6:105–121. doi: 10.1016/j.jare.2013.07.006. PubMed DOI PMC

Kopeček J. Hydrogel biomaterials: A smart future? Biomaterials. 2007;28:5185–5192. doi: 10.1016/j.biomaterials.2007.07.044. PubMed DOI PMC

Wichterle O., Lím D. Hydrophilic Gels for Biological Use. Nature. 1960;185:117–118. doi: 10.1038/185117a0. DOI

Geckil H., Xu F., Zhang X., Moon S., Demirci U. Engineering hydrogels as extracellular matrix mimics. Nanomedicine. 2010;5:469–484. doi: 10.2217/nnm.10.12. PubMed DOI PMC

Oh J.K., Drumright R., Siegwart D.J., Matyjaszewski K. The development of microgels/nanogels for drug delivery applications. Prog. Polym. Sci. 2008;33:448–477. doi: 10.1016/j.progpolymsci.2008.01.002. DOI

Vinogradov S.V., Bronich T.K., Kabanov A.V. Nanosized cationic hydrogels for drug delivery: Preparation, properties and interactions with cells. Adv. Drug Deliver. Rev. 2002;54:135–147. doi: 10.1016/S0169-409X(01)00245-9. PubMed DOI

Tokarev I., Minko S. Stimuli-responsive hydrogel thin films. Soft Matter. 2009;5:511–524. doi: 10.1039/B813827C. DOI

Ishihara K., Ueda T., Nakabayashi N. Preparation of Phospholipid Polylners and Their Properties as Polymer Hydrogel Membranes. Polym. J. 1990;22:355–360. doi: 10.1295/polymj.22.355. DOI

Klouda L., Mikos A.G. Thermoresponsive hydrogels in biomedical applications. Eur. J. Pharm. Biopharm. 2008;68:34–45. doi: 10.1016/j.ejpb.2007.02.025. PubMed DOI PMC

Klouda L. Thermoresponsive hydrogels in biomedical applications. Eur. J. Pharm. Biopharm. 2015;97:338–349. doi: 10.1016/j.ejpb.2015.05.017. PubMed DOI

Qiu Y., Park K. Environment-sensitive hydrogels for drug delivery. Adv. Drug Deliver. Rev. 2001;53:321–339. doi: 10.1016/S0169-409X(01)00203-4. PubMed DOI

Gupta P., Vermani K., Garg S. Hydrogels: From controlled release to pH-responsive drug delivery. Drug Discov. Today. 2002;7:569–579. doi: 10.1016/S1359-6446(02)02255-9. PubMed DOI

Miyata T., Asami N., Uragami T. A reversibly antigen-responsive hydrogel. Nature. 1999;399:766–769. doi: 10.1038/21619. PubMed DOI

Miyata T., Uragami T., Nakamae K. Biomolecule-sensitive hydrogels. Adv. Drug Deliver. Rev. 2002;54:79–98. doi: 10.1016/S0169-409X(01)00241-1. PubMed DOI

Spiller K.L., Laurencin S.J., Charlton D., Maher S.A., Lowman A.M. Superporous hydrogels for cartilage repair: Evaluation of the morphological and mechanical properties. Acta Biomater. 2008;4:17–25. doi: 10.1016/j.actbio.2007.09.001. PubMed DOI

Chen J., Park H., Park K. Synthesis of superporous hydrogels: Hydrogels with fast swelling and superabsorbent properties. J. Biomed. Mater. Res. 1999;44:53–62. doi: 10.1002/(SICI)1097-4636(199901)44:1<53::AID-JBM6>3.0.CO;2-W. PubMed DOI

Petka W.A., Harden J.L., McGrath K.P., Wirtz D., Tirrell D.A. Reversible Hydrogels from Self-Assembling Artificial Proteins. Science. 1998;281:389–392. doi: 10.1126/science.281.5375.389. PubMed DOI

Ehrick J.D., Deo S.K., Browning T.W., Bachas L.G., Madou M.J., Daunert S. Genetically engineered protein in hydrogels tailors stimuli-responsive characteristics. Nat. Mater. 2005;4:298–302. doi: 10.1038/nmat1352. PubMed DOI

Gong J.P., Katsuyama Y., Kurokawa T., Osada Y. Double-Network Hydrogels with Extremely High Mechanical Strength. Adv. Mater. 2003;15:1155–1158. doi: 10.1002/adma.200304907. DOI

Yasuda K., Ping Gong J., Katsuyama Y., Nakayama A., Tanabe Y., Kondo E., Ueno M., Osada Y. Biomechanical properties of high-toughness double network hydrogels. Biomaterials. 2005;26:4468–4475. doi: 10.1016/j.biomaterials.2004.11.021. PubMed DOI

Lee K.Y., Mooney D.J. Hydrogels for Tissue Engineering. Chem. Rev. 2001;101:1869–1880. doi: 10.1021/cr000108x. PubMed DOI

Drury J.L., Mooney D.J. Hydrogels for tissue engineering: Scaffold design variables and applications. Biomaterials. 2003;24:4337–4351. doi: 10.1016/S0142-9612(03)00340-5. PubMed DOI

Slaughter B.V., Khurshid S.S., Fisher O.Z., Khademhosseini A., Peppas N.A. Hydrogels in Regenerative Medicine. Adv. Mater. 2009;21:3307–3329. doi: 10.1002/adma.200802106. PubMed DOI PMC

Annabi N., Tamayol A., Uquillas J.A., Akbari M., Bertassoni L.E., Cha C., Camci-Unal G., Dokmeci M.R., Peppas N.A., Khademhosseini A. 25th Anniversary Article: Rational Design and Applications of Hydrogels in Regenerative Medicine. Adv. Mater. 2014;26:85–124. doi: 10.1002/adma.201303233. PubMed DOI PMC

van der Linden H.J., Herber S., Olthuis W., Bergveld P. Stimulus-sensitive hydrogels and their applications in chemical (micro)analysis. Analyst. 2003;128:325–331. doi: 10.1039/b210140h. PubMed DOI

Rubina A.Y., Pan’kov S.V., Dementieva E.I., Pen’kov D.N., Butygin A.V., Vasiliskov V.A., Chudinov A.V., Mikheikin A.L., Mikhailovich V.M., Mirzabekov A.D. Hydrogel drop microchips with immobilized DNA: Properties and methods for large-scale production. Anal. Biochem. 2004;325:92–106. doi: 10.1016/j.ab.2003.10.010. PubMed DOI

Wang K.L., Burban J.H., Cussler E.L. Responsive Gels: Volume Transitions II. Springer; Berlin/Heidelberg, Germany: 1993. Hydrogels as separation agents; pp. 67–79.

Ozay O., Ekici S., Baran Y., Kubilay S., Aktas N., Sahiner N. Utilization of magnetic hydrogels in the separation of toxic metal ions from aqueous environments. Desalination. 2010;260:57–64. doi: 10.1016/j.desal.2010.04.067. DOI

Hoare T.R., Kohane D.S. Hydrogels in drug delivery: Progress and challenges. Polymer. 2008;49:1993–2007. doi: 10.1016/j.polymer.2008.01.027. DOI

Narayanaswamy R., Torchilin V.P. Hydrogels and Their Applications in Targeted Drug Delivery. Molecules. 2019;24:603. doi: 10.3390/molecules24030603. PubMed DOI PMC

Li J., Mooney D.J. Designing hydrogels for controlled drug delivery. Nat. Rev. Mater. 2016;1:1–17. doi: 10.1038/natrevmats.2016.71. PubMed DOI PMC

Trongsatitkul T., Budhlall B.M. Microgels or microcapsules? Role of morphology on the release kinetics of thermoresponsive PNIPAm-co-PEGMa hydrogels. Polym. Chem. 2013;4:1502–1516. doi: 10.1039/C2PY20889J. DOI

Perugini P., Genta I., Conti B., Modena T., Pavanetto F. Long-term release of clodronate from biodegradable microspheres. AAPS PharmSciTech. 2001;2:6–14. doi: 10.1208/pt020310. PubMed DOI PMC

Lee B.H., Lee Y.M., Sohn Y.S., Song S.-C. A Thermosensitive Poly(organophosphazene) Gel. Macromolecules. 2002;35:3876–3879. doi: 10.1021/ma012093q. DOI

Andrade-Vivero P., Fernandez-Gabriel E., Alvarez-Lorenzo C., Concheiro A. Improving the Loading and Release of NSAIDs from pHEMA Hydrogels by Copolymerization with Functionalized Monomers. J. Pharm. Sci. 2007;96:802–813. doi: 10.1002/jps.20761. PubMed DOI

Sato T., Uchida R., Tanigawa H., Uno K., Murakami A. Application of polymer gels containing side-chain phosphate groups to drug-delivery contact lenses. J. Appl. Polym. Sci. 2005;98:731–735. doi: 10.1002/app.22080. DOI

Young S., Wong M., Tabata Y., Mikos A.G. Gelatin as a delivery vehicle for the controlled release of bioactive molecules. J. Control. Release. 2005;109:256–274. doi: 10.1016/j.jconrel.2005.09.023. PubMed DOI

Jenkins A.D., Kratochvíl P., Stepto R.F.T., Suter U.W. Glossary of basic terms in polymer science (IUPAC Recommendations 1996) Pure Appl. Chem. 1996;68:2287–2311. doi: 10.1351/pac199668122287. DOI

Zoratto N., Matricardi P. Polymeric Gels. Woodhead Publishing; Cambridge, UK: 2018. Semi-IPNs and IPN-based hydrogels; pp. 91–124. PubMed

Aminabhavi T.M., Nadagouda M.N., More U.A., Joshi S.D., Kulkarni V.H., Noolvi M.N., Kulkarni P.V. Controlled release of therapeutics using interpenetrating polymeric networks. Expert Opin. Drug Deliv. 2015;12:669–688. doi: 10.1517/17425247.2014.974871. PubMed DOI

Rinaudo M. Main properties and current applications of some polysaccharides as biomaterials. Polym. Int. 2008;57:397–430. doi: 10.1002/pi.2378. DOI

Zarrintaj P., Manouchehri S., Ahmadi Z., Saeb M.R., Urbanska A.M., Kaplan D.L., Mozafari M. Agarose-based biomaterials for tissue engineering. Carbohydr. Polym. 2018;187:66–84. doi: 10.1016/j.carbpol.2018.01.060. PubMed DOI

Wang N., Wu X.S. Preparation and Characterization of Agarose Hydrogel Nanoparticles for Protein and Peptide Drug Delivery. Pharm. Dev. Technol. 1997;2:135–142. doi: 10.3109/10837459709022618. PubMed DOI

Liang S., Xu J., Weng L., Dai H., Zhang X., Zhang L. Protein diffusion in agarose hydrogel in situ measured by improved refractive index method. J. Control. Release. 2006;115:189–196. doi: 10.1016/j.jconrel.2006.08.006. PubMed DOI

Marras-Marquez T., Peña J., Veiga-Ochoa M.D. Agarose drug delivery systems upgraded by surfactants inclusion: Critical role of the pore architecture. Carbohydr. Polym. 2014;103:359–368. doi: 10.1016/j.carbpol.2013.12.026. PubMed DOI

Meilander N.J., Yu X., Ziats N.P., Bellamkonda R.V. Lipid-based microtubular drug delivery vehicles. J. Control. Release. 2001;71:141–152. doi: 10.1016/S0168-3659(01)00214-0. PubMed DOI

Narahashi T., Yamada M., Frazier D.T. Cationic Forms of Local Anaesthetics block Action Potentials from Inside the Nerve Membrane. Nature. 1969;223:748–749. doi: 10.1038/223748a0. PubMed DOI

Gunasekaran P., Rajasekaran G., Han E.H., Chung Y.-H., Choi Y.-J., Yang Y.J., Lee J.E., Kim H.N., Lee K., Kim J.-S., et al. Cationic Amphipathic Triazines with Potent Anti-bacterial, Anti-inflammatory and Anti-atopic Dermatitis Properties. Sci. Rep. 2019;9:1292. doi: 10.1038/s41598-018-37785-z. PubMed DOI PMC

Broderick E., Lyons H., Pembroke T., Byrne H., Murray B., Hall M. The characterisation of a novel, covalently modified, amphiphilic alginate derivative, which retains gelling and non-toxic properties. J. Colloid Interface Sci. 2006;298:154–161. doi: 10.1016/j.jcis.2005.12.026. PubMed DOI

Aymard P., Martin D.R., Plucknett K., Foster T.J., Clark A.H., Norton I.T. Influence of thermal history on the structural and mechanical properties of agarose gels. Biopolymers. 2001;59:131–144. doi: 10.1002/1097-0282(200109)59:3<131::AID-BIP1013>3.0.CO;2-8. PubMed DOI

Lapasin R., Pricl S. Rheology of Industrial Polysaccharides: Theory and Applications. Springer; Boston, MA, USA: 1995.

Pescosolido L., Feruglio L., Farra R., Fiorentino S., Colombo I., Coviello T., Matricardi P., Hennink W.E., Vermonden T., Grassi M. Mesh size distribution determination of interpenetrating polymer network hydrogels. Soft Matter. 2012;8:7708–7715. doi: 10.1039/c2sm25677k. DOI

Draper N.R., Smith H. Applied Regression Analysis. John Wiley & Sons, Inc; New York, NY, USA: 1996.

Sedláček P., Smilek J., Klučáková M. How the interactions with humic acids affect the mobility of ionic dyes in hydrogels—2. Non-stationary diffusion experiments. React. Funct. Polym. 2014;75:41–50. doi: 10.1016/j.reactfunctpolym.2013.12.002. DOI

Smilek J., Sedláček P., Kalina M., Klučáková M. On the role of humic acids’ carboxyl groups in the binding of charged organic compounds. Chemosphere. 2015;138:503–510. doi: 10.1016/j.chemosphere.2015.06.093. PubMed DOI

Sedláček P., Smilek J., Laštůvková M., Kalina M., Klučáková M. Hydrogels: Invaluable experimental tool for demonstrating diffusion phenomena in physical chemistry laboratory courses. J. Mater. Educ. 2017;39:59–90.

Crank J. The Mathematics of Diffusion. Oxford University Press Inc; New York, NY, USA: 1979.

ImageJ Website. [(accessed on 20 August 2020)]; Available online: https://imagej.nih.gov/ij/

Schneider C.A., Rasband W.S., Eliceiri K.W. NIH Image to ImageJ: 25 years of image analysis. Nat. Methods. 2012;9:671–675. doi: 10.1038/nmeth.2089. PubMed DOI PMC

Normand V., Lootens D.L., Amici E., Plucknett K.P., Aymard P. New Insight into Agarose Gel Mechanical Properties. Biomacromolecules. 2000;1:730–738. doi: 10.1021/bm005583j. PubMed DOI

Grillet A.M., Wyatt N.B., Gloe L.M. Rheology. InTech; Rijeka, Croatia: 2012. Polymer Gel Rheology and Adhesion; pp. 59–80.

Weng L., Chen X., Chen W. Rheological Characterization of in Situ Crosslinkable Hydrogels Formulated from Oxidized Dextran and N -Carboxyethyl Chitosan. Biomacromolecules. 2007;8:1109–1115. doi: 10.1021/bm0610065. PubMed DOI PMC

Trenkmann I., Bok S., Korampally V.R., Gangopadhyay S., Graaf H., von Borczyskowski C. Counting single Rhodamine 6G dye molecules in organosilicate nanoparticles. Chem. Phys. 2012;406:41–46. doi: 10.1016/j.chemphys.2012.02.014. PubMed DOI PMC

Penzkofer A., Leupacher W. Fluorescence behaviour of highly concentrated rhodamine 6G solutions. J. Lumin. 1987;37:61–72. doi: 10.1016/0022-2313(87)90167-0. DOI

Doty P., Steiner R.F. Light Scattering and Spectrophotometry of Colloidal Solutions. J. Chem. Phys. 1950;18:1211–1220. doi: 10.1063/1.1747913. DOI

Horne D.S. Determination of the fractal dimension using turbidimetric techniques. Application to aggregating protein systems. Faraday Discuss. Chem. Soc. 1987;83:259–280. doi: 10.1039/dc9878300259. DOI

Camerini-Otero R.D., Day L.A. The wavelength dependence of the turbidity of solutions of macromolecules. Biopolymers. 1978;17:2241–2249. doi: 10.1002/bip.1978.360170916. DOI

Leone M., Sciortino F., Migliore M., Fornili S.L., Vittorelli M.B.P. Order parameters of gels and gelation kinetics of aqueous agarose systems: Relation to the spinodal decomposition of the sol. Biopolymers. 1987;26:743–761. doi: 10.1002/bip.360260513. DOI

Aymard P., Williams M.A.K., Clark A.H., Norton I.T. A Turbidimetric Study of Phase Separating Biopolymer Mixtures during Thermal Ramping. Langmuir. 2000;16:7383–7391. doi: 10.1021/la000549b. DOI

Singh T.R.R. Hydrogels. CRC Press; Boca Raton, FL, USA: 2018.

Stellwagen N.C. Effect of the electric field on the apparent mobility of large DNA fragments in agarose gels. Biopolymers. 1985;24:2243–2255. doi: 10.1002/bip.360241207. PubMed DOI

Flory P.J. Principles of Polymer Chemistry. Cornell University Press; Ithaca, New York, NY, USA: 1953.

Larson R.G. The Structure and Rheology of Complex Fluids. Oxford University Press Inc.; New York, NY, USA: 1999.

Chai Q., Jiao Y., Yu X. Hydrogels for Biomedical Applications: Their Characteristics and the Mechanisms behind Them. Gels. 2017;3:6. doi: 10.3390/gels3010006. PubMed DOI PMC

Calhoun M.A., Bentil S.A., Elliott E., Otero J.J., Winter J.O., Dupaix R.B. Beyond linear elastic modulus: Viscoelastic models for brain and brain mimetic hydrogels. ACS Biomater. Sci. Eng. 2019;5:3964–3973. doi: 10.1021/acsbiomaterials.8b01390. PubMed DOI

Smilek J., Jarábková S., Velcer T., Pekař M. Compositional and Temperature Effects on the Rheological Properties of Polyelectrolyte–Surfactant Hydrogels. Polymers. 2019;11:927. doi: 10.3390/polym11050927. PubMed DOI PMC

Galway M.E., Heckman J.W., Jr., Hyde G.J., Fowke L.C. Methods in Cell Biology. Volume 49. Academic Press; Cambridge, MA, USA: 1995. Advances in high-pressure and plunge-freeze fixation; pp. 3–19. PubMed DOI

Hrubanova K., Nebesarova J., Ruzicka F., Krzyzanek V. The innovation of cryo-SEM freeze-fracturing methodology demonstrated on high pressure frozen biofilm. Micron. 2018;110:28–35. doi: 10.1016/j.micron.2018.04.006. PubMed DOI

Paradossi G., Cavalieri F., Chiessi E., Spagnoli C., Cowman M.K. Poly (vinyl alcohol) as versatile biomaterial for potential biomedical applications. J. Mater. Sci. Mater. 2003;14:687–691. doi: 10.1023/A:1024907615244. PubMed DOI

Holly F.J., Refojo M.F. Wettability of hydrogels I. Poly(2-hydroxyethyl methacrylate) J. Biomed. Mater. Res. 1975;9:315–326. doi: 10.1002/jbm.820090307. PubMed DOI

Zhu J. Bioactive modification of poly(ethylene glycol) hydrogels for tissue engineering. Biomaterials. 2010;31:4639–4656. doi: 10.1016/j.biomaterials.2010.02.044. PubMed DOI PMC

Osmałek T., Froelich A., Tasarek S. Application of gellan gum in pharmacy and medicine. Int. J. Pharm. 2014;466:328–340. doi: 10.1016/j.ijpharm.2014.03.038. PubMed DOI

Park H., Park K., Shalaby W.S.W. Biodegradable Hydrogels for Drug Delivery. CRC Press; Boca Raton, FL, USA: 2011.

Xiong X.Y., Tam K.C., Gan L.H. Polymeric Nanostructures for Drug Delivery Applications Based on Pluronic Copolymer Systems. J. Nanosci. Nanotechno. 2006;6:2638–2650. doi: 10.1166/jnn.2006.449. PubMed DOI

Amiji M., Tailor R., Ly M.-K., Goreham J. Gelatin-Poly(Ethylene Oxide) Semi-interpenetrating Polymer Network with pH-Sensitive Swelling and Enzyme-Degradable Properties for Oral Drug Delivery. Drug Dev. Ind. Pharm. 1997;23:575–582. doi: 10.3109/03639049709149822. DOI

Elisseeff J., McIntosh W., Anseth K., Riley S., Ragan P., Langer R. Photoencapsulation of chondrocytes in poly(ethylene oxide)-based semi-interpenetrating networks. J. Biomed. Mater. Res. 2000;51:164–171. doi: 10.1002/(SICI)1097-4636(200008)51:2<164::AID-JBM4>3.0.CO;2-W. PubMed DOI

Sedláček P., Smilek J., Klučáková M. How the interactions with humic acids affect the mobility of ionic dyes in hydrogels—Results from diffusion cells. React. Funct. Polym. 2013;73:1500–1509. doi: 10.1016/j.reactfunctpolym.2013.07.008. DOI

Larrañeta E., Stewart S., Ervine M., Al-Kasasbeh R., Donnelly R. Hydrogels for Hydrophobic Drug Delivery. Classification, Synthesis and Applications. J. Funct. Biomater. 2018;9:13. doi: 10.3390/jfb9010013. PubMed DOI PMC

Venerová T., Pekař M. Rheological properties of gels formed by physical interactions between hyaluronan and cationic surfactants. Carbohydr. Polym. 2017;170:176–181. doi: 10.1016/j.carbpol.2017.04.087. PubMed DOI

Enev V., Sedláček P., Jarábková S., Velcer T., Pekař M. ATR-FTIR spectroscopy and thermogravimetry characterization of water in polyelectrolyte-surfactant hydrogels. Colloids Surf. A. 2019;575:1–9. doi: 10.1016/j.colsurfa.2019.04.089. DOI

Moschakis T. Microrheology and particle tracking in food gels and emulsions. Curr. Opin. Colloid Interface Sci. 2013;18:311–323. doi: 10.1016/j.cocis.2013.04.011. DOI

Rathgeber S., Beauvisage H.-J., Chevreau H., Willenbacher N., Oelschlaeger C. Microrheology with Fluorescence Correlation Spectroscopy. Langmuir. 2009;25:6368–6376. doi: 10.1021/la804170k. PubMed DOI

García-Aparicio C., Quijada-Garrido I., Garrido L. Diffusion of small molecules in a chitosan/water gel determined by proton localized NMR spectroscopy. J. Colloid Interface Sci. 2012;368:14–20. doi: 10.1016/j.jcis.2011.11.028. PubMed DOI

Severs N., Shotton D. Rapid Freezing of Biological Specimens for Freeze Fracture and Deep Etching. Cell Biol. 2006;3:249–255.

Landry M.R. Thermoporometry by differential scanning calorimetry: Experimental considerations and applications. Thermochim. Acta. 2005;433:27–50. doi: 10.1016/j.tca.2005.02.015. DOI

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