Skip to main content
SpringerLink
Log in

Core–shell drug carrier from folate conjugated chitosan obtained from prawn shell for targeted doxorubicin delivery

  • Clinical Applications of Biomaterials
  • Original Research
  • Published:
Journal of Materials Science: Materials in Medicine Aims and scope Submit manuscript

Abstract

A multifunctional drug carrier with dual targeting (magnetic and folate-receptor) and pH sensitive core-shell hybrid nanomaterial has been developed to carry an anticancer drug doxorubicin.Superparamagnetic iron oxide nanoparticles (IONPs) were used as core of the carrier and cross-linked folate conjugated chitosan (FA-CS) was acted as shell in which doxorubicin was physically entrapped. Transmission electron microscopy (TEM) analysis confirmed the average particle size of IONPs and FA-CS coated IONPs 8.2 and 15.4 nm respectively. Magnetic measurement indicated that both the IONPs and FA-CS coated IONPs were superparamagnetic at room temperature with a magnetization value 57.72 and 37.44 emu/g respectively. At pH 5.8 (malignant tissue) showed a burst release of 30.05% of the doxorubicin in the first 4 h followed by a sustained release of 88.26% of drug over 72 h. From these results it is expected that doxorubicin loaded nanoparticles can be a promising drug carrier for the treatment of solid tumors with the ability to reduce toxic side effects of drugs by selective targeting and sustained release.

Graphical abstract

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

Scheme 1
Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  1. Kumar DG, Naresh R, Varma KR, Nagasen D, Sudheer B, Kishore VS. Modifications of chitosan for use in nanoparticulate drug delivery systems. Int J Pharm Sci Nanotechnol. 2013;6:2210.

    Google Scholar 

  2. Hu X, Liu S, Huang Y, Chen X, Jing X. Biodegradable block copolymer-doxorubicin conjugates via different linkages: preparation, characterization, and in vitro evaluation. Biomacromolecules. 2010;11:2094.

    Article  Google Scholar 

  3. Rao N V, Mane S, Kishore A, Das Sarma J, Shunmugam R. Norbornene derived doxorubicin copolymers as drug carriers with pH responsive hydrazone linker. Biomacromolecules. 2011;13:221.

    Article  Google Scholar 

  4. Vllasaliu D, Casettari L, Bonacucina G, Cespi M, Filippo Palmieri G, Illum L. Folic acid conjugated chitosan nanoparticles for tumor targeting of therapeutic and imaging agents. Pharm Nanotechnol. 2013;1:184.

    Article  Google Scholar 

  5. Ma H, Liu Y, Shi M, et al. Theranostic, pH-responsive, doxorubicin-loaded nanoparticles inducing active targeting and apoptosis for advanced gastric cancer. Biomacromolecules. 2015;16:4022.

    Article  Google Scholar 

  6. Sun C, Lee JSH, Zhang M. Magnetic nanoparticles in MR imaging and drug delivery. Adv Drug Deliv Rev. 2008;60:1252.

    Article  Google Scholar 

  7. Greco F, Vicent MJ, Gee S, et al. Investigating the mechanism of enhanced cytotoxicity of HPMA copolymer-Dox-AGM in breast cancer cells. J Control Release. 2007;117:28.

    Article  Google Scholar 

  8. Yu X, Pishko MV. Nanoparticle-based biocompatible and targeted drug delivery: characterization and in vitro studies. Biomacromolecules. 2011;12:3205.

    Article  Google Scholar 

  9. Dash M, Chiellini F, Ottenbrite RM, Chiellini E. Chitosan-A versatile semi-synthetic polymer in biomedical applications. Prog Polym Sci. 2011;36:981.

    Article  Google Scholar 

  10. Wang S, Low PS. Folate-mediated targeting of antineoplastic drugs, imaging agents, and nucleic acids to cancer cells. J Control Release. 1998;53:39.

    Article  Google Scholar 

  11. Yoo HS, Park TG. Folate receptor targeted biodegradable polymeric doxorubicin micelles. J Control Release. 2004;96:273.

    Article  Google Scholar 

  12. Ye W-l, Du J-b, Na R, et al. Cellular uptake and antitumor activity of DOX-hyd-PEG-FA nanoparticles. PLoS One. 2014;9:e97358.

    Article  Google Scholar 

  13. Pillai CKS, Paul W, Sharma CP. Chitin and chitosan polymers: Chemistry, solubility and fiber formation. Prog Polym Sci. 2009;34:641.

    Article  Google Scholar 

  14. Tannock IF, Rotin D. Acid pH in tumors and its potential for therapeutic exploitation. Cancer Res. 1989;49:4373.

    Google Scholar 

  15. Mascolo MC, Pei Y, Ring TA. Room temperature co-precipitation synthesis of magnetite nanoparticles in a large pH window with different bases. Materials. 2013;6:5549.

    Article  Google Scholar 

  16. Rashid TU, Rahman MM, Kabir S, Shamsuddin SM, Khan MA. A new approach for the preparation of chitosan from y irradiation of prawn shell: effects of radiation on the characteristics of chitosan. Polym Int. 2012;61:1302.

    Article  Google Scholar 

  17. Zu Y, Zhao Q, Zhao X, Zu S, Meng L. Process optimization for the preparation of oligomycin-loaded folate-conjugated chitosan nanoparticles as a tumor-targeted drug delivery system using a two-level factorial design method. Int J Nanomedicine. 2011;6:3429.

    Article  Google Scholar 

  18. Lee RJ, Low PS. Delivery of liposomes into cultured KB cells via folate receptor-mediated endocytosis. J Biol Chem. 1994;269:3198.

    Google Scholar 

  19. Li P, Wang Y, Zeng F, Chen L, Peng Z, Kong LX. Synthesis and characterization of folate conjugated chitosan and cellular uptake of its nanoparticles in HT-29 cells. Carbohydr Res. 2011;346:801.

    Article  Google Scholar 

  20. Kuo C-H, Liu Y-C, Chang C-MJ, Chen J-H, Chang C, Shieh C-J. Optimum conditions for lipase immobilization on chitosan-coated Fe3O4 nanoparticles. Carbohyd Polym. 2012;87:2538.

    Article  Google Scholar 

  21. Unsoy G, Khodadust R, Yalcin S, Mutlu P, Gunduz U. Synthesis of Doxorubicin loaded magnetic chitosan nanoparticles for pH responsive targeted drug delivery. Eur J Pharm Sci. 2014;62:243.

    Article  Google Scholar 

  22. Mashhadizadeh MH, Amoli-Diva M. Drug-carrying amino silane coate d magnetic nanoparticles as potential vehicles for delivery of antibiotics. J Nanomed Nanotechnol. 2012;3:2.

    Article  Google Scholar 

  23. Jadhav N, Chodankar V. Design of chitosan based and rographolides microparticles for targetted delivery to lung tumour. Int J Pharm Pharm Sci. 2012;4:163.

    Google Scholar 

  24. Czechowska-Biskup R, Jarosinska D, Rokita Be, Ulanski P, Rosiak JM. Determination of degree of deacetylation of chitosan-comparision of methods. Prog Chem Appl Chitin Deriv. 2012;17:5.

    Google Scholar 

  25. Ahn Y, Choi EJ, Kim EH. Superparamagnetic relaxation in cobalt ferrite nanoparticles synthesized from hydroxide carbonate precursors. Rev Adv Mater Sci. 2003;5:477.

    Google Scholar 

  26. Yu BY, Kwak S-Y. Assembly of magnetite nanocrystals into spherical mesoporous aggregates with a 3-D wormhole-like pore structure. J Mater Chem. 2010;20:8320.

    Article  Google Scholar 

  27. Vaidyanathan G, Sendhilnathan S, Arulmurugan R. Structural and magnetic properties of Co1- xZnxFe2O4 nanoparticles by co-precipitation method. J Magn Magn Mater. 2007;313:293.

    Article  Google Scholar 

  28. Jordan A, Scholz R, Wust P, Fahling H, Felix R. Magnetic fluid hyperthermia (MFH): Cancer treatment with AC magnetic field induced excitation of biocompatible superparamagnetic nanoparticles. J Magn Magn Mater. 1999;201:413.

    Article  Google Scholar 

  29. Pan C, Hu B, Li W, Sun YI, Ye H, Zeng X. Novel and efficient method for immobilization and stabilization of B-d-galactosidase by covalent attachment onto magnetic Fe3O4-chitosan nanoparticles. J Mol Catal B. 2009;61:208.

    Article  Google Scholar 

  30. Tripathi S, Mehrotra GK, Dutta PK. Physicochemical and bioactivity of cross-linked chitosan-PVA film for food packaging applications. Int J Biol Macromol. 2009;45:372.

    Article  Google Scholar 

  31. Ye X-R, Daraio C, Wang C, Talbot JB, Jin S. Room temperature solvent-free synthesis of monodisperse magnetite nanocrystals. J Nanosci Nanotechnol. 2006;6:852.

    Article  Google Scholar 

  32. Safari J, Javadian L. Chitosan decorated Fe3O4 nanoparticles as a magnetic catalyst in the synthesis of phenytoin derivatives. RSC Adv. 2014;4:48973.

    Article  Google Scholar 

  33. Pradhan P, Giri J, Samanta G, et al. Comparative evaluation of heating ability and biocompatibility of different ferrite-based magnetic fluids for hyperthermia application. J Biomed Mater Res Part B. 2007;81:12.

    Article  Google Scholar 

  34. Aydin R, Pulat M. 5-Fluorouracil encapsulated chitosan nanoparticles for pH-stimulated drug delivery: evaluation of controlled release kinetics. J Nanomater. 2012;2012:42.

    Google Scholar 

  35. Berger JRM, Reist M, Mayer JM, Felt O, Peppas NA, Gurny R. Structure and interactions in covalently and ionically crosslinked chitosan hydrogels for biomedical applications. Eur J Pharm Biopharm. 2004;57:19.

    Article  Google Scholar 

Download references

Acknowledgements

The author highly acknowledge to the Ministry of Science and Technology (S&T), Bangladesh for their research grant (EAS-05) for the year 2014-2016 in the form of Special Allocation to carry out this research project.

Author information

Authors and Affiliations

  1. Department of Applied Chemistry and Chemical Engineering, Faculty of Engineering and Technology, University of Dhaka, Dhaka, 1000, Bangladesh

    Md. Sazedul Islam, Papia Haque, Taslim U. Rashid, M. Nuruzzaman Khan, Abul K. Mallik & Mohammed Mizanur Rahman

  2. Material Science Division, Atomic Energy Centre, Bangladesh Atomic Energy Commission, Dhaka, 1000, Bangladesh

    M. Nazrul I. Khan

  3. Designated Reference Institute for Chemical Measurements (DRICM), Bangladesh Council of Scientific and Industrial Research (BCSIR), Dr. Kudrat-e-Khoda Road, Dhaka, 1205, Bangladesh

    Mala Khan

Authors
  1. Md. Sazedul Islam
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Papia Haque
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Taslim U. Rashid
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M. Nuruzzaman Khan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Abul K. Mallik
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. M. Nazrul I. Khan
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Mala Khan
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Mohammed Mizanur Rahman
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Papia Haque or Mohammed Mizanur Rahman.

Ethics declarations

Conflict of interest

The authors declare that they have no competing interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Islam, M.S., Haque, P., Rashid, T.U. et al. Core–shell drug carrier from folate conjugated chitosan obtained from prawn shell for targeted doxorubicin delivery. J Mater Sci: Mater Med 28, 55 (2017). https://doi.org/10.1007/s10856-017-5859-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s10856-017-5859-x

Keywords

Search

Navigation