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Investigating the effect of freezing temperature and cross-linking on modulating drug release from chitosan scaffolds

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Abstract

The aim of this study was to investigate the effect of altering design variables like cross-linking and freezing temperature (at a time) on morphology of freeze-dried chitosan scaffolds and modulation of release of Diclofenac sodium (model drug). Freeze-dried chitosan scaffolds produced at − 80 °C, cross-linked with genipin, showed swelling of 163.52 ± 9.95% with sustained drug release of 26.37 ± 10.47% over 24 h (P < 0.05). In comparison, uncross-linked scaffolds produced at − 80 °C showed higher swelling of 173.58 ± 8.23% and drug release of 28.67 ± 2.40% (P < 0.05). Uncross-linked scaffolds produced using freezing temperature of − 20 °C also showed higher swelling of 228.77 ± 9.84% and release of 30.58 ± 3.25% (P < 0.05). Release kinetics followed Higuchi model with Fickian diffusion, thereby indicating a swelling-dependent release. Altering the design parameters also showed significant changes in pore size and porosity, thereby supporting the swelling and drug delivery behavior from scaffolds.

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References

  • Ahmed EM (2015) Hydrogel preparation, characterization, and applications. J Adv Res 6:105–121

    CAS  PubMed  Google Scholar 

  • Ali A, Ahmed S (2018) A review on chitosan and its nanocomposites in drug delivery. Int J Biol Macromol 109:273–286

    CAS  PubMed  Google Scholar 

  • Angulo DEL, Sobral PJA (2016) The effect of processing parameters and solid concentration on the microstructure and pore architecture of gelatin-chitosan scaffolds produced by freeze drying. Mat Res 19:839–845

    Google Scholar 

  • Annabi N, Nichol JW, Zhong X, Ji C, Koshy S, Khademhosseini A, Dehghani F (2010) Controlling the porosity and microarchitecture of hydrogels for tissue engineering. Tissue Eng Part B 16:371–383

    CAS  Google Scholar 

  • Azevedog EPD (2015) Chitosan hydrogels for drug delivery and tissue engineering applications. Int J Pharm Pharm Sci 7:8–14

    Google Scholar 

  • Bharatham BH, Bakar ZA, Perimal EK, Yusof LM, Hamid M (2014) Development and characterization of novel porous 3D alginate-cockle shell powder nanobiocomposite bone scaffold. Biomed Res Int 2014:1–11

    Google Scholar 

  • Campos MGN, Satsangi N, Rawls HR, Mei LHI (2009) Chitosan cross-linked films for drug delivery application. Macromol Symp 279:169–174

    CAS  Google Scholar 

  • Costa P, Lobo J (2001) Modelling and comparison of dissolution profiles. Eur J Pharm Sci 13:123–133

    CAS  Google Scholar 

  • Dathathri E, Nayak RR, Philip JA, Thakur G, Koteshwara KB (2016) A comparative release study of curcumin and diclofenac sodium from genipin cross-linked composite hydrogel. In: Proceedings of the 2016 IEEE Students’ Technology Symposium; 2016 Sept 30–Oct 2; Kharagpur, India, pp 106–109

  • Datta P, Thakur G, Chatterjee J, Dhara S (2014) Biofunctional phosphorylated chitosan hydrogels prepared above pH 6 and effect of crosslinkers on gel properties towards biomedical applications. Soft Mater 12:27–35

    CAS  Google Scholar 

  • Delgadillo-Armendariz NL, Rangel-Vazquez NA, Marquez-Brazon EA, Gascue BR (2014) Interactions of chitosan/genipin hydrogels during drug delivery: a QSPR approach. Quim Nova 4:1503–1509

    Google Scholar 

  • Dhandayuthapani B, Yoshida Y, Maekawa T, Kumar DS (2011) Polymeric scaffolds in tissue engineering application: a review. Int J Polym Sci 2011:1–19

    Google Scholar 

  • Garg T, Singh O, Arora S, Murthy RSR (2012a) Scaffold: a novel carrier for cell and drug delivery. Crit Rev Ther Drug Carrier Syst 29:1–63

    CAS  PubMed  Google Scholar 

  • Garg T, Chanana A, Joshi R (2012b) Preparation of chitosan scaffolds for tissue engineering using freeze drying technology. IOSR J Pharm 2:72–73

    Google Scholar 

  • Garg T, Singh S, Goyal AK (2013) Stimuli-sensitive hydrogels: an excellent carrier for drug and cell delivery. Crit Rev Ther Drug Carrier Syst 30(5):369–409

    CAS  PubMed  Google Scholar 

  • Giri TK, Thakur A, Alexander A, Badwaik AH, Tripathi DK (2012) Modified chitosan hydrogels as drug delivery and tissue engineering systems: present status and applications. Acta Pharm Sin B 2:439–449

    CAS  Google Scholar 

  • Goni MG, Tomadoni B, Roura SI, Moreira MR (2017) Lactic acid as potential substitute of acetic acid for dissolution of chitosan: preharvest application to Butterhead lettuce. J Food Sci Technol 54(3):620–626

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ikeda T, Ikeda K, Yamamoto K, Ishizaki H, Yoshizawa Y, Yanagiguchi K, Yamada S, Hayashi Y (2014) Fabrication and characteristics of chitosan sponge as a tissue engineering scaffold. Biomed Res Int 2014:1–8

    Google Scholar 

  • James HP, John R, Alex A, Anoop KR (2014) Smart polymers for the controlled delivery of drugs—a concise review. Acta Pharm Sin B 4:120–127

    Google Scholar 

  • Khan TA, Peh KK, Ch’ng HS (2000) Mechanical, bioadhesive strength and biological evaluations of chitosan films for wound dressing. J Pharm Pharm Sci 3(3):303–311

    CAS  PubMed  Google Scholar 

  • Kinikoglu B, Rodriguez-Cabello JC, Damour O, Hasirci V (2011) A smart bilayer scaffold of elastin-like recombinamer and collagen for soft tissue engineering. J Mater Sci Mater Med 22:1541–1554

    CAS  PubMed  Google Scholar 

  • Klein MP, Hackenhaar CR, Lorenzoni ASG, Rodrigues RC, Costa TMH, Ninow JL, Hertz PF (2016) Chitosan crosslinked with genipin as support matrix for application in food process: support characterization and β-d-galactosidase immobilization. Carbohydr Polym 137:184–190

    CAS  PubMed  Google Scholar 

  • Li J, Cai C, Li J, Li J, Li J, Sun T, Wang L, Wu H, Yu G (2018) Chitosan-based nanomaterials for drug delivery. Molecules 23(10):2661

    PubMed Central  Google Scholar 

  • Ma L, Gao C, Mao Z, Zhou J, Shen J, Hu X, Han C (2003) Collagen/chitosan porous scaffolds with improved biostability for skin tissue engineering. Biomaterials 24:4833–4841

    CAS  PubMed  Google Scholar 

  • Mao JS, Zhao LG, Yin YJ, Yao KD (2003) Structure and properties of bilayer chitosan-gelatin scaffolds. Biomaterials 24:1067–1074

    CAS  PubMed  Google Scholar 

  • Mody VV (2010) Introduction of polymeric drug delivery. AKS Publication [Internet]. http://www.akspublication.com. Accessed Jul 2016

  • Mody VV (2010) Introduction of polymeric drug delivery. AKS Publication. http://www.akspublication.com. Accessed July 2016

  • Muzzarelli RAA (2009) Genipin-crosslinked chitosan hydrogels as biomedical and pharmaceutical aids. Carbohyd Polym 77(1):1–9

    CAS  Google Scholar 

  • Muzzarelli RAA, Mehtedi ME, Bottegoni C, Aquili A, Gigante A (2015) Genipin-crosslinked chitosan gels and scaffolds for tissue engineering and regeneration of cartilage and bone. Mar Drugs 13:7314–7338

    CAS  PubMed  PubMed Central  Google Scholar 

  • Narayanaswamy R, Torchilin VP (2019) Hydrogels and their applications in targeted drug delivery. Molecules 24(3):603

    PubMed Central  Google Scholar 

  • Nguyen VC, Nguyen VB, Hsieh MF (2013) Curcumin-loaded chitosan/gelatin composite sponge for wound healing application. Int J Polym Sci 2013:1–7

    Google Scholar 

  • O’Brien FJ (2011) Biomaterials and scaffolds for tissue engineering. Mater Today 14:88–95

    Google Scholar 

  • Oungbho K, Mueller BW (1996) Chitosan-gelatin sponges as drug carrier systems. Eur J Pharm Sci 4:S155

    Google Scholar 

  • Prabaharan M (2015) Characterizations of tissue scaffolds drug release profiles. In: Tomlins P (ed) Characterization and design of tissue scaffolds. Elsevier Woodhead Publishing, Amsterdam, pp 149–165

    Google Scholar 

  • Riva R, Ragelle H, Rieux AD, Duhem N, Jerome C, Preat V (2011) Chitosan and chitosan derivatives in drug delivery and tissue engineering. In: Jayakumar R, Prabaharan M, Muzzarelli RAA (eds) Advances in polymer science. Springer, Berlin Heidelberg, pp 19–44

    Google Scholar 

  • Rufato KB, Galdino JP, Ody KS, Pereira AG, Corradini E, Martins AF, Paulino AT, Fajardo AR, Aouada FA, La Porta FA, Rubira AF, Muniz EC (2018) Hydrogels based on chitosan and chitosan derivatives for biomedical applications, hydrogels—smart materials for biomedical applications. IntechOpen, London

    Google Scholar 

  • Soundrapandian C, Datta S, Kundu B, Basu D, Sa B (2010) Porous bioactive glass scaffolds for local drug delivery in osteomyelitis: development and in vitro characterization. AAPS PharmSciTech 2:1675–1683

    Google Scholar 

  • Sultana N, Wang M (2011) Water uptake and diffusion in PHBV tissue engineering scaffolds and non-porous thin films. In: Proceedings of international conference on biomedical engineering and technology IPCBEE, 2011 June 4–5, Singapore, pp 24–28

  • Thakur G, Rousseau D (2016) Hydrogels: characterization, drug delivery, and tissue engineering applications. In: Misra M (ed) Encyclopedia of biomedical polymers and polymeric biomaterials. Taylor and Francis, New York, pp 3853–3878

    Google Scholar 

  • Thakur G, Mitra A, Rousseau D, Basak A, Sarkar S, Pal K (2011) Crosslinking of gelatin-based drug carriers by genipin induces changes in drug kinetic profiles in vitro. J Mater Sci Mater Med 22:115–123

    CAS  PubMed  Google Scholar 

  • Thakur G, Mitra A, Basak A, Sheet D (2012a) Characterization and scanning electron microscopic investigation of crosslinked freeze dried gelatin matrices for study of drug diffusivity and release kinetics. Micron 43:311–320

    CAS  PubMed  Google Scholar 

  • Thakur G, Naqvi MA, Rousseau D, Pal K, Mitra A, Basak A (2012b) Gelatin-based emulsion gels for diffusion-controlled release applications. J Biomater Sci Polym Ed 23:645–661

    CAS  PubMed  Google Scholar 

  • Thakur G, Rousseau D, Rafanan RR (2013) Gelatin based matrices for drug delivery applications. In: Boran G (ed) Gelatin: production, applications and health implications. Nova Science Publishers Inc., New York, pp 49–70

    Google Scholar 

  • Vogelson CT (2001) Advances in drug delivery systems. Mod Drug Discov 4:49–50

    CAS  Google Scholar 

  • Wattanutchariya W, Changkowchai W (2014) Characterization of porous scaffold from chitosan-gelatin/hydroxyapatite for bone grafting. In: Proceedings of the international multiconference of engineers and computer scientists; 2014 March 12–14, Hong Kong, pp 1073–1077

  • Zhang D, Sun P, Li P, Xue A, Zhang X, Zhang H (2013) A magnetic chitosan hydrogel for sustained and prolonged delivery of bacillus Calmette–Guerin in the treatment of bladder cancer. Biomaterials 34:10258–10266

    CAS  PubMed  Google Scholar 

  • Zhang W, Ren G, Xu H, Zhang J, Liu H, Mu S, Cai X, Wu T (2016) Genipin cross-linked chitosan hydrogel for the controlled release of tetracycline with controlled release property, lower cytotoxicity, and long-term bioactivity. J Polym Res 23:156

    Google Scholar 

Download references

Acknowledgements

The authors sincerely acknowledge Mr. Shivanand. M. Shettigar, Manipal College of Pharmaceutical Sciences, Manipal for technical support.

Funding

This work was supported by Manipal University under the Grant MIT/AD-R&C/Post Doc/2012, dated 30.11.2012.

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Authors and Affiliations

  1. Department of Biomedical Engineering, Manipal Institute of Technology, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India

    Eshwari Dathathri, Goutam Thakur & Fiona Concy Rodrigues

  2. Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India

    K. B. Koteshwara

  3. Department of Chemistry, Manipal Institute of Technology, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India

    N. V. Anil Kumar

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  1. Eshwari Dathathri
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  2. Goutam Thakur
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  3. K. B. Koteshwara
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  4. N. V. Anil Kumar
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  5. Fiona Concy Rodrigues
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Correspondence to Goutam Thakur.

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Dathathri, E., Thakur, G., Koteshwara, K.B. et al. Investigating the effect of freezing temperature and cross-linking on modulating drug release from chitosan scaffolds. Chem. Pap. 74, 1759–1768 (2020). https://doi.org/10.1007/s11696-019-01024-0

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