Skip to main content
SpringerLink
Log in

Injectable all-polysaccharide self-assembling hydrogel: a promising scaffold for localized therapeutic proteins

  • Original Research
  • Published:
Cellulose Aims and scope Submit manuscript

Abstract

Biomedical/pharmaceutical applications demand hydrogels made from biobased materials without the use of potentially toxic or denaturizing crosslinking agents. In this work, a new all-polysaccharide self-assembling hydrogel system consisting of anionic TEMPO-oxidized cellulose nanofibers (TOCNs) and cationic guar gum (CGG) is proposed. The TOCNs/CGG hydrogel are formed in situ when TOCNs and CGG are mixed, due to the electrostatic interactions and abundant hydrogen bondings therein. Interactions in the hydrogel were supported by Fourier transform infrared spectroscopy (FTIR) results. The as-prepared hydrogel showed good injectability, self-healing performance and reasonable mechanical properties. Scanning electron microscope (SEM) images illustrated the network structure of the hydrogel. Furthermore, the TOCNs/CGG hydrogel system was studied for protein drug release, in which bovine serum albumin (BSA) was used as a model drug to examine the drug release performance in buffers at pH 2.0 or 7.4, simulating gastrointestinal tract conditions. The results indicate its sustained drug releasing ability. A mathematical analysis of the release results supports an anomalous transport mechanism for the TOCNs/CGG hydrogel system.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Altunbas A, Lee SJ, Rajasekaran SA, Schneider JP, Pochan DJ (2011) Encapsulation of curcumin in self-assembling peptide hydrogels as injectable drug delivery vehicles. Biomaterials 32(25):5906–5914

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bian H, Wei L, Lin C, Ma Q, Dai H, Zhu JY (2018) Lignin-containing cellulose nanofibril-reinforced polyvinyl alcohol hydrogels. Acs Sustain Chem Eng 6(4):4821–4828

    Article  CAS  Google Scholar 

  • Branco MC, Schneider JP (2009) Self-assembling materials for therapeutic delivery. Acta Biomater 5(3):817–831

    Article  CAS  PubMed  Google Scholar 

  • Branco MC, Pochan DJ, Wagner NJ, Schneider JP (2010) The effect of protein structure on their controlled release from an injectable peptide hydrogel. Biomaterials 31(36):9527–9534

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen S-C, Wu Y-C, Mi F-L, Lin Y-H, Yu L-C, Sung H-W (2004) A novel pH-sensitive hydrogel composed of N, O-carboxymethyl chitosan and alginate cross-linked by genipin for protein drug delivery. J Controll Release 96(2):285–300

    Article  CAS  Google Scholar 

  • Chen J, Ma X, Dong Q, Song D, Hargrove D, Vora SR, Ma AWK, Lu X, Lei Y (2016) Self-healing of thermally-induced, biocompatible and biodegradable protein hydrogel. RSC Adv 6(61):56183–56192

    Article  CAS  Google Scholar 

  • Dai L, Long Z, Zhao Y, Wang B, Chen J (2016) Comparison of hydroxypropyl and carboxymethyl guar for the preparation of nanocellulose composite films. Cellulose 23:1–11

    Article  CAS  Google Scholar 

  • Dai L, Long Z, Chen J, An X, Cheng D, Khan A, Ni Y (2017a) Robust guar gum/cellulose nanofibrils multilayer films with good barrier properties. ACS Appl Mater Interfaces 9:5477–5485

    Article  CAS  PubMed  Google Scholar 

  • Dai L, Zhang L, Wang B, Yang B, Khan I, Khan A, Ni Y (2017b) Multifunctional self-assembling hydrogel from guar gum. Chem Eng J 330:1044–1051

    Article  CAS  Google Scholar 

  • De France KJ, Hoare T, Cranston ED (2017) Review of hydrogels and aerogels containing nanocellulose. Chem Mater 29(11):4609–4631

    Article  CAS  Google Scholar 

  • Eskandari S, Guerin T, Toth I, Stephenson RJ (2017) Recent advances in self-assembled peptides: implications for targeted drug delivery and vaccine engineering. Adv Drug Deliv Rev 110–111:169–187

    Article  CAS  PubMed  Google Scholar 

  • Friend DR (2005) New oral delivery systems for treatment of inflammatory bowel disease. Adv Drug Deliv Rev 57(2):247–265

    Article  CAS  PubMed  Google Scholar 

  • Gupta D, Tator CH, Shoichet MS (2006) Fast-gelling injectable blend of hyaluronan and methylcellulose for intrathecal, localized delivery to the injured spinal cord. Biomaterials 27(11):2370–2379

    Article  CAS  PubMed  Google Scholar 

  • Habibi N, Kamaly N, Memic A, Shafiee H (2016) Self-assembled peptide-based nanostructures: smart nanomaterials toward targeted drug delivery. Nano Today 11(1):41–60

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hakkarainen T, Koivuniemi R, Kosonen M, Escobedo-Lucea C, Sanz-Garcia A, Vuola J, Valtonen J, Tammela P, Mäkitie A, Luukko K, Yliperttula M, Kavola H (2016) Nanofibrillar cellulose wound dressing in skin graft donor site treatment. J Control Release 244:292–301

    Article  CAS  PubMed  Google Scholar 

  • Hamidi M, Azadi A, Rafiei P (2008) Hydrogel nanoparticles in drug delivery. Adv Drug Deliv Rev 60:1638–1649

    Article  CAS  PubMed  Google Scholar 

  • Huang X, Brazel CS (2001) On the importance and mechanisms of burst release in matrix-controlled drug delivery systems. J Control Release 73(2):121–136

    Article  CAS  PubMed  Google Scholar 

  • Huang Y, Yu H, Xiao C (2007) pH-sensitive cationic guar gum/poly (acrylic acid) polyelectrolyte hydrogels: swelling and in vitro drug release. Carbohydr Polym 69(4):774–783

    Article  CAS  Google Scholar 

  • Huang C, Bai H, Li C, Shi G (2011a) A graphene oxide/hemoglobin composite hydrogel for enzymatic catalysis in organic solvents. Chem Commun (Camb) 47(17):4962–4964

    Article  CAS  Google Scholar 

  • Huang R, Qi W, Feng L, Su R, He Z (2011b) Self-assembling peptide–polysaccharide hybrid hydrogel as a potential carrier for drug delivery. Soft Matter 7(13):6222–6230

    Article  CAS  Google Scholar 

  • Jradi K, Maury C, Daneault C (2015) Contribution of TEMPO-oxidized cellulose gel in the formation of flower-like zinc oxide superstructures: characterization of the TOCgel/ZnO composite films. Appl Sci 5(4):1164

    Article  CAS  Google Scholar 

  • Kholiya F, Chaudhary JP, Vadodariya N, Meena R (2016) Synthesis of bio-based aldehyde from seaweed polysaccharide and its interaction with bovine serum albumin. Carbohydr Polym 150:278–285

    Article  CAS  PubMed  Google Scholar 

  • Kim W, Kim M, Tae G (2017) Injectable system and its potential application for the delivery of biomolecules by using thermosensitive poly(γ-glutamic acid)-based physical hydrogel. Int J Biol Macromol 110:457–464

    Article  CAS  PubMed  Google Scholar 

  • Li J (2010) Self-assembled supramolecular hydrogels based on polymer–cyclodextrin inclusion complexes for drug delivery. NPG Asia Mater 2:112

    Article  Google Scholar 

  • Li Z, Hou Z, Fan H, Li H (2016) Organic-inorganic hierarchical self-assembly into robust luminescent supramolecular hydrogel. Adv Func Mater 27:1604379

    Article  CAS  Google Scholar 

  • Lin N, Gèze A, Wouessidjewe D, Huang J, Dufresne A (2016) Biocompatible double-membrane hydrogels from cationic cellulose nanocrystals and anionic alginate as complexing drugs codelivery. ACS Appl Mater Interfaces 8(11):6880–6889

    Article  CAS  PubMed  Google Scholar 

  • Lu L, Unsworth LD (2016) pH-triggered release of hydrophobic molecules from self-assembling hybrid nanoscaffolds. Biomacromolecules 17(4):1425–1436

    Article  CAS  PubMed  Google Scholar 

  • Lü S, Gao C, Xu X, Bai X, Duan H, Gao N, Feng C, Xiong Y, Liu M (2015) Injectable and Self-healing carbohydrate-based hydrogel for cell encapsulation. ACS Appl Mater Interfaces 7(23):13029–13037

    Article  CAS  PubMed  Google Scholar 

  • Masruchin N, Park B-D, Causin V, Um IC (2015) Characteristics of TEMPO-oxidized cellulose fibril-based hydrogels induced by cationic ions and their properties. Cellulose 22(3):1993–2010

    Article  CAS  Google Scholar 

  • Panda JJ, Mishra A, Basu A, Chauhan VS (2008) Stimuli responsive self-assembled hydrogel of a low molecular weight free dipeptide with potential for tunable drug delivery. Biomacromol 9(8):2244–2250

    Article  CAS  Google Scholar 

  • Powell LC, Khan S, Chinga-Carrasco G, Wright CJ, Hill KE, Thomas DW (2016) An investigation of Pseudomonas aeruginosa biofilm growth on novel nanocellulose fibre dressings. Carbohydr Polym 137:191–197

    Article  CAS  PubMed  Google Scholar 

  • Rodríguez R, Alvarez-Lorenzo C, Concheiro A (2003) Influence of cationic cellulose structure on its interactions with sodium dodecylsulfate: implications on the properties of the aqueous dispersions and hydrogels. Eur J Pharm Biopharm 56(1):133–142

    Article  CAS  PubMed  Google Scholar 

  • Saito T, Kimura S, Nishiyama Y, Isogai Akira (2007) Cellulose nanofibers prepared by TEMPO-mediated oxidation of native cellulose. Biomacromol 8:2485–2491

    Article  CAS  Google Scholar 

  • Saracino GAA, Cigognini D, Silva D, Caprini A, Gelain F (2013) Nanomaterials design and tests for neural tissue engineering. Chem Soc Rev 42(1):225–262

    Article  CAS  PubMed  Google Scholar 

  • Serra L, Domenech J, Peppas NA (2006) Drug transport mechanisms and release kinetics from molecularly designed poly(acrylic acid-g-ethylene glycol) hydrogels. Biomaterials 27:5440–5451

    Article  CAS  PubMed  Google Scholar 

  • Siepmann J, Peppas NA (2012) Modeling of drug release from delivery systems based on hydroxypropyl methylcellulose (HPMC). Adv Drug Deliv Rev 64(Supplement):163–174

    Article  Google Scholar 

  • Singh VK, Banerjee I, Agarwal T, Pramanik K, Bhattacharya MK, Pal K (2014) Guar gum and sesame oil based novel bigels for controlled drug delivery. Colloids Surf B Biointerfaces 123:582–592

    Article  CAS  PubMed  Google Scholar 

  • Siro I, Plackett D (2010) Microfibrillated cellulose and new nanocomposite materials: a review. Cellulose 17(3):459–494

    Article  CAS  Google Scholar 

  • Steinhilber D, Rossow T, Wedepohl S, Paulus F, Seiffert S, Haag R (2013) A microgel construction kit for bioorthogonal encapsulation and pH-controlled release of living cells. Angew Chem Int Ed 52(51):13538–13543

    Article  CAS  Google Scholar 

  • Torre PMDL, Enobakhare Y, Torrado G, Torrado S (2003) Release of amoxicillin from polyionic complexes of chitosan and poly(acrylic acid). Study of polymer/polymer and polymer/drug interactions within the network structure. Biomaterials 24(8):1499–1506

    Article  PubMed  Google Scholar 

  • Wang C, Li X, Du B, Li P, Li H (2013) Associating and rheological behaviors of fluorinated cationic guar gum in aqueous solutions. Carbohydr Polym 95(2):637–643

    Article  CAS  PubMed  Google Scholar 

  • Wei H, Du S, Liu Y, Zhao H, Chen C, Li Z, Lin J, Zhang Y, Zhang J, Wan X (2014) Tunable, luminescent, and self-healing hybrid hydrogels of polyoxometalates and triblock copolymers based on electrostatic assembly. Chem Commun (Camb) 50(12):1447–1450

    Article  CAS  Google Scholar 

  • Xiang B, He K, Zhu R, Liu Z, Zeng S, Huang Y, Nie Z, Yao S (2016) Self-assembled DNA hydrogel based on enzymatically polymerized DNA for protein encapsulation and enzyme/DNAzyme hybrid cascade reaction. ACS Appl Mater Interfaces 8(35):22801–22807

    Article  CAS  PubMed  Google Scholar 

  • Xing R, Liu K, Jiao T, Zhang N, Ma K, Zhang R, Zou Q, Ma G, Yan X (2016) An injectable self-assembling collagen-gold hybrid hydrogel for combinatorial antitumor photothermal/photodynamic therapy. Adv Mater 28(19):3669–3676

    Article  CAS  PubMed  Google Scholar 

  • Yang J, Han C (2016) Mechanically viscoelastic properties of cellulose nanocrystals skeleton reinforced hierarchical composite hydrogels. ACS Appl Mater Interfaces 8(38):25621–25630

    Article  CAS  PubMed  Google Scholar 

  • Yang B, Zhang Y, Zhang X, Tao L, Li S, Wei Y (2012) Facilely prepared inexpensive and biocompatible self-healing hydrogel: a new injectable cell therapy carrier. Polym Chem 3(12):3235–3238

    Article  CAS  Google Scholar 

  • Yi J-Z, Zhang L-M (2007) Biodegradable blend films based on two polysaccharide derivatives and their use as ibuprofen-releasing matrices. J Appl Polym Sci 103(6):3553–3559

    Article  CAS  Google Scholar 

  • Zhang X-Z, Wu D-Q, Chu C-C (2004) Synthesis, characterization and controlled drug release of thermosensitive IPN–PNIPAAm hydrogels. Biomaterials 25(17):3793–3805

    Article  CAS  PubMed  Google Scholar 

  • Zhao W, Glavas L, Odelius K, Edlund U, Albertsson A-C (2014) Facile and green approach towards electrically conductive hemicellulose hydrogels with tunable conductivity and swelling behavior. Chem Mater 26(14):4265–4273

    Article  CAS  Google Scholar 

  • Zhao W, Li X, Gao S, Feng Y, Huang J (2017) Understanding mechanical characteristics of cellulose nanocrystals reinforced PHEMA nanocomposite hydrogel: in aqueous cyclic test. Cellulose 24(5):2095–2110

    Article  CAS  Google Scholar 

  • Zou X, Zhao X, Ye L, Wang Q, Li H (2015) Preparation and drug release behavior of pH-responsive bovine serum albumin-loaded chitosan microspheres. J Ind Eng Chem 21:1389–1397

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The authors acknowledge the financial support from the Canada Research Chairs Program, the Opening Project of Guangxi Key Laboratory of Clean Pulp & Papermaking and Pollution Control (No. KF201819-3), High-level Foreign Experts Project (GDT20186100425) and Key Scientific Research Group of Shaanxi Province (2017KCT-02).

Author information

Authors and Affiliations

  1. College of Bioresources Chemical and Materials Engineering, Shaanxi University of Science and Technology, Xi’an, 710021, China

    Lei Dai, Ting Cheng, Yan Wang, Chao Duan & Yonghao Ni

  2. Guangxi Key Laboratory of Clean Pulp & Papermaking and Pollution Control, College of Light Industry and Food Engineering, Guangxi University, Nanning, 530004, China

    Lei Dai & Shuangxi Nie

  3. Department of Chemical Engineering, University of New Brunswick, Fredericton, NB, E3B 5A3, Canada

    Lei Dai & Yonghao Ni

  4. Jiangsu Co-Innovation Center of Efficient Processing and Utilization of Forest Resources, Nanjing Forestry University, Nanjing, 210037, China

    Hailong Lu

  5. Academy of Science and Technology, Hangzhou Dianzi University, Hangzhou, 310018, China

    Hong He

Authors
  1. Lei Dai
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ting Cheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yan Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hailong Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Shuangxi Nie
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hong He
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Chao Duan
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Yonghao Ni
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Lei Dai, Chao Duan or Yonghao Ni.

Ethics declarations

Conflict of interest

The authors declare that there is no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 2751 kb)

Supplementary material 2 (AVI 12839 kb)

Supplementary material 3 (AVI 2444 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Dai, L., Cheng, T., Wang, Y. et al. Injectable all-polysaccharide self-assembling hydrogel: a promising scaffold for localized therapeutic proteins. Cellulose 26, 6891–6901 (2019). https://doi.org/10.1007/s10570-019-02579-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10570-019-02579-7

Keywords

Search

Navigation