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Evaluation of solute diffusion and polymer relaxation in cross-linked hyaluronic acid hydrogels: experimental measurement and relaxation modeling

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Abstract

Evaluation of transport properties of a drug in a hydrogel matrix is of engineering importance in the assessment of drug delivery systems. Water sorption and solute release are the two important aspects that determine the transport of water/solute in a hydrogel. A novel custom-made diffusion cell is used to examine the transport properties in the hydrogels by chemically cross-linking hyaluronic acid in various alkaline solutions at different cross-linker-to-polymer ratios. The tracer diffusion coefficient in the swollen hydrogel matrix in its rubbery state is estimated using a custom-made diffusional cell. The release kinetics is followed at perfect sink conditions, which transform from a glassy polymer dry membrane state to a swollen rubbery gel state. It is shown that the diffusion of solvent (water) through the hydrogel is case II transport, while the diffusion through the swollen hydrogel is case I (Fickian). The diffusion coefficient is proved to be independent of mesh size and pH of the initial solution. However, the release kinetics is influenced by the diffusion of solute and the relaxation of the polymer in hydrogel. The relaxation coefficient is a function of alkalinity in the solution with which the gel is being made. The contribution of relaxation to the transport during solvent sorption and solute release is found to be similar.

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References

  1. Jin W, Lee D, Jeon Y, Park DH (2020) Biocompatible hydrotalcite nanohybrids for medical functions. Minerals 10(2):172

    CAS  Google Scholar 

  2. Patil SB, Inamdar SZ, Das KK, Akamanchi KG, Patil AV, Inamadar AC, Reddy KR, Raghu AV, Kulkarni RV (2020) Tailor-made electrically-responsive poly (acrylamide)-graft-pullulan copolymer based transdermal drug delivery systems: synthesis, characterization, in-vitro and ex-vivo evaluation. J Drug Deliv Sci Technol 56:101525

    CAS  Google Scholar 

  3. Dave V, Gupta A, Singh P, Gupta C, Sadhu V, Reddy KR (2019) Synthesis and characterization of celecoxib loaded PEGylated liposome nanoparticles for biomedical applications. Nano-Struct. Nano-Objects 18:100288

    CAS  Google Scholar 

  4. Dave V, Sohgaura A, Tak K, Reddy KR, Thylur RP, Ramachandraiah K, Sadhu V (2019) Ethosomal polymeric patch containing losartan potassium for the treatment of hypertension: in-vitro and in-vivo evaluation. Biomed Phys Eng Express 5(6):065029

    Google Scholar 

  5. Gulla S, Lomada D, Srikanth VV, Shankar MV, Reddy KR, Soni S, Reddy MC (2018) Recent advances in nanoparticles-based strategies for cancer therapeutics and antibacterial applications. In: Methods in microbiology, vol 46, Elsevier, pp 255–293

  6. Paliwal S, Tilak A, Sharma J, Dave V, Sharma S, Verma K, Tak K, Reddy KR, Sadhu V (2019) Flurbiprofen-loaded ethanolic liposome particles for biomedical application. J Microbiol Methods 161:18

    CAS  PubMed  Google Scholar 

  7. Hasnain MS, Nayak AK (2019) Natural Polysaccharides in Drug Delivery and Biomedical Applications. In: Natural polysaccharides in drug delivery and biomedical applications. Academic Press

  8. Silva ASG, Pinheiro MNC (2013) Diffusion coefficients of timolol maleate in polymeric membranes based on methacrylate hydrogels. J Chem Eng Data 58(8):2280

    CAS  Google Scholar 

  9. Davis EM, Minelli M, Giacinti Baschetti M, Elabd YA (2013) Non-Fickian diffusion of water in polylactide. Ind Eng Chem Res 52(26):8664

    CAS  Google Scholar 

  10. Phadke KV, Manjeshwar LS, Aminabhavi TM (2014) Microspheres of gelatin and poly(ethylene glycol) coated with ethyl cellulose for controlled release of metronidazole. Ind Eng Chem Res 53(16):6575

    CAS  Google Scholar 

  11. Wu L, Brazel CS (2008) Mathematical model to predict drug release, including the early-time burst effect, from swellable homogeneous hydrogels. Ind Eng Chem Res 47(5):1518

    CAS  Google Scholar 

  12. Huin-Amargier C, Marchal P, Payan E, Netter P, Dellacherie E, Biomed J (2006) New physically and chemically crosslinked hyaluronate (HA)-based hydrogels for cartilage repair. Mater Res Part A 76(2):416

    Google Scholar 

  13. Shimojo AAM, Pires AMB, Lichy R, Rodrigues AA, Santana MHA, Biomed J (2014) The crosslinking degree controls the mechanical, rheological, and swelling properties of hyaluronic acid microparticles. Mater Res Part A 00A:1

    Google Scholar 

  14. Amin S, Rajabnezhad S, Kohli K (2009) Hydrogels as potential drug delivery systems. Sci Res Essays 4(11):1175

    Google Scholar 

  15. Nimmo CM, Owen SC, Shoichet MS (2011) Diels– Alder click cross-linked hyaluronic acid hydrogels for tissue engineering. Biomacromolecules 12(3):824

    CAS  PubMed  Google Scholar 

  16. Jeon O, Song SJ, Lee KJ, Park MH, Lee SH, Hahn SK, Kim S, Kim BS (2007) Mechanical properties and degradation behaviors of hyaluronic acid hydrogels cross-linked at various cross-linking densities. Carbohydr Polym 70(3):251

    CAS  Google Scholar 

  17. Collins MN, Birkinshaw C (2008) Investigation of the swelling behavior of crosslinked hyaluronic acid films and hydrogels produced using homogeneous reactions. J Appl Polym Sci 109(2):923

    CAS  Google Scholar 

  18. Collins MN, Birkinshaw C (2013) Hyaluronic acid based scaffolds for tissue engineering—a review. Carbohydr Polym 92(2):1262

    CAS  PubMed  Google Scholar 

  19. Sannino A, Madaghiele M, Conversano F, Mele G, Maffezzoli A, Netti P, Ambrosio L, Nicolais L (2004) Cellulose derivative-hyaluronic acid-based microporous hydrogels cross-linked through divinyl sulfone (DVS) to modulate equilibrium sorption capacity and network stability. Biomacromolecules 5(1):92

    CAS  PubMed  Google Scholar 

  20. Saraydin D, Çaldiran Y (2001) In vitro dynamic swelling behaviors of polyhydroxamic acid hydrogels in the simulated physiological body fluids. Polym Bull 46(1):91

    CAS  Google Scholar 

  21. Hallinan DT, De Angelis MG, Giacinti Baschetti M, Sarti GC, Elabd YA (2010) Non-Fickian diffusion of water in nafion. Macromolecules 43(10):4667

    CAS  Google Scholar 

  22. Potreck J, Uyar F, Sijbesma H, Nijmeijer K, Stamatialis D, Wessling M (2009) Sorption induced relaxations during water diffusion in S-PEEK. Phys Chem Chem Phys 11(2):298

    CAS  PubMed  Google Scholar 

  23. Ochiuz L, Popa G, Stoleriu I, Tomoiagă AM, Popa M (2013) Microencapsulation of metoprolol tartrate into chitosan for improved oral administration and patient compliance. Ind Eng Chem Res 52(49):17432

    CAS  Google Scholar 

  24. Singh B, Chauhan N, Sharma V (2011) Design of molecular imprinted hydrogels for controlled release of cisplatin: evaluation of network density of hydrogels. Ind Eng Chem Res 50(24):13742

    CAS  Google Scholar 

  25. Bisschops MAT, Luyben KCAM, van der Wielen LAM (1998) Generalized Maxwell–Stefan approach for swelling kinetics of dextran gels. Ind Eng Chem Res 37(8):3312

    CAS  Google Scholar 

  26. Zarzycki R, Rogacki G, Modrzejewska Z, Nawrotek K (2011) Modeling of drug (albumin) release from thermosensitive chitosan hydrogels. Ind Eng Chem Res 50(9):5866

    CAS  Google Scholar 

  27. Wack H, Ulbricht M (2007) New hydrogels based on substituted anhydride modified collagen and 2-hydroxyethyl methacrylate: synthesis and characterization. Ind Eng Chem Res 46(1):359

    CAS  Google Scholar 

  28. Gatej I, Popa M, Rinaudo M (2005) Role of the pH on hyaluronan behavior in aqueous solution. Biomacromolecules 6(1):61

    CAS  PubMed  Google Scholar 

  29. Sotoudeh S, Pourfallah G, Barati A, Davarnejad R, Farahani MA, Memar A (2010) Dynamical modeling and experimental analysis on the swelling behavior of the sIPN hydrogels. Ind Eng Chem Res 49(20):10111

    CAS  Google Scholar 

  30. Khan S, Ranjha N (2014) Effect of degree of cross-linking on swelling and on drug release of low viscous chitosan/poly(vinyl alcohol) hydrogels. Polym Bull 71(8):2133

    CAS  Google Scholar 

  31. Matos MA, White LR, Tilton RD (2006) Electroosmotically enhanced mass transfer through polyacrylamide gels. J Colloid Interface Sci 300(1):429

    CAS  PubMed  Google Scholar 

  32. Crank J et al (1979) The mathematics of diffusion. Oxford University Press, Oxford

    Google Scholar 

  33. Martinez-Ruvalcaba A, Sanchez-Diaz J, Becerra F, Cruz-Barba L, Gonzalez-Alvarez A (2009) Swelling characterization and drug delivery kinetics of polyacrylamide-co-itaconic acid/chitosan hydrogels. Express Polym Lett 3(1):25

    CAS  Google Scholar 

  34. Ritger PL, Peppas NA (1987) Transport of penetrants in the macromolecular structure of coals: 4. Models for analysis of dynamic penetrant transport. Fuel 66(6):815

    CAS  Google Scholar 

  35. Kajjari PB, Manjeshwar LS, Aminabhavi TM (2011) Semi-interpenetrating polymer network hydrogel blend microspheres of gelatin and hydroxyethyl cellulose for controlled release of theophylline. Ind Eng Chem Res 50(13):7833

    CAS  Google Scholar 

  36. Sullad AG, Manjeshwar LS, Aminabhavi TM (2011) Novel semi-interpenetrating microspheres of dextran-grafted-acrylamide and poly (vinyl alcohol) for controlled release of abacavir sulfate. Ind Eng Chem Res 50(21):11778

    CAS  Google Scholar 

  37. Gates G, Harmon J, Ors J, Benz P (2003) 2,3-dihydroxypropyl methacrylate and 2-hydroxyethyl methacrylate hydrogels: gel structure and transport properties. Polymer 44(1):215

    CAS  Google Scholar 

  38. Singh B, Sharma V (2014) Correlation study of structural parameters of bioadhesive polymers in designing a tunable drug delivery system. Langmuir 30(28):8580

    CAS  PubMed  Google Scholar 

  39. Xu Y, Chen C, Li J (2007) Sorption and diffusion characteristics of water vapor in dense polyimide membranes. J Chem Eng Data 52(6):2146

    CAS  Google Scholar 

  40. Xu Y, Shang T, Chen C, Li J (2006) Dynamic sorption and anomalous diffusion of small molecules in dense polyimide membranes. J Chem Eng Data 51(6):2016

    Google Scholar 

  41. Lu Z, Chen W, Hamman JH (2010) Chitosan-polycarbophil interpolyelectrolyte complex as a matrix former for controlled release of poorly water-soluble drugs I: in vitro evaluation. Drug Dev Ind Pharm 36(5):539

    CAS  PubMed  Google Scholar 

  42. Brazel CS, Peppas NA (2000) Modeling of drug release from swellable polymers. Eur J Pharm Biopharm 49(1):47

    CAS  PubMed  Google Scholar 

  43. Razavilar N, Choi P (2014) In-vitro modeling of the release kinetics of micron and nano-sized polymer drug carriers. Int J Drug Deliv 5(4):362

    Google Scholar 

  44. Hajova H, Chmelar J, Nistor A, Gregor T, Kosek J (2013) Experimental study of sorption and diffusion of n-pentane in polystyrene. J Chem Eng Data 58(4):851

    CAS  Google Scholar 

  45. Pamfil D, Schick C, Vasile C (2014) New hydrogels based on substituted anhydride modified collagen and 2-hydroxyethyl methacrylate: synthesis and characterization. Ind Eng Chem Res 53(28):11239

    CAS  Google Scholar 

  46. Deen GR, Lim EK, Mah CH, Heng KM (2012) New cationic linear copolymers and hydrogels of n vinyl caprolactam and N-acryloyl N ethyl piperazine: synthesis, reactivity, influence of external stimuli on the LCST and swelling properties. Ind Eng Chem Res 51(41):13354

    CAS  Google Scholar 

  47. Kajjari PB, Manjeshwar LS, Aminabhavi TM (2011) Novel interpenetrating polymer network hydrogel microspheres of chitosan and poly(acrylamide)-grafted-guar gum for controlled release of ciprofloxacin. Ind Eng Chem Res 50(23):13280

    CAS  Google Scholar 

  48. Paul D (2011) Elaborations on the Higuchi model for drug delivery. Int J Pharm 418(1):13

    CAS  PubMed  Google Scholar 

  49. Higuchi T (1961) Rate of release of medicaments from ointment bases containing drugs in suspension. J Pharm Sci 50(10):874

    CAS  PubMed  Google Scholar 

  50. Maleki A, Kjøniksen AL, Nyström B (2008) Effect of pH on the behavior of hyaluronic acid in dilute and semidilute aqueous solutions. In: Macromol Symp, vol 274. Wiley Online Library, pp 131–140

  51. Nguyen MK, Lee DS (2010) Injectable biodegradable hydrogels. Macromol Biosci 10(6):563

    CAS  PubMed  Google Scholar 

  52. de Beer D, Stoodley P, Lewandowski Z (1997) Measurement of local diffusion coefficients in biofilms by microinjection and confocal microscopy. Biotechnol Bioeng 53(2):151

    PubMed  Google Scholar 

  53. Banks DS, Fradin C (2005) Anomalous diffusion of proteins due to molecular crowding. Biophys J 89(5):2960

    CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The authors strongly acknowledge the efforts made by Mr. Shobhit Kumar and Mr. Shubham Verma, undergraduate students, in validating the diffusion equations.

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  1. Department of Chemical Engineering, University of Petroleum and Energy Studies, Via Prem Nagar, Bidholi, Dehradun, India

    Jagadeeshwar Kodavaty

  2. Department of Chemical Engineering, Indian Institute of Technology Madras, Chennai, India

    Abhijit P. Deshpande

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  1. Jagadeeshwar Kodavaty
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Correspondence to Jagadeeshwar Kodavaty.

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Kodavaty, J., Deshpande, A.P. Evaluation of solute diffusion and polymer relaxation in cross-linked hyaluronic acid hydrogels: experimental measurement and relaxation modeling. Polym. Bull. 78, 2605–2626 (2021). https://doi.org/10.1007/s00289-020-03224-1

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