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Calcium alginate/dextran methacrylate IPN beads as protecting carriers for protein delivery

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Abstract

In the present study, mechanical and protein delivery properties of a system based on the interpenetration of calcium-alginate (Ca-Alg) and dextran-methacrylate (Dex-MA) networks are shown. Interpenetrated hydrogels beads were prepared by means of the alginate chains crosslinking with calcium ions, followed by the exposure to UV light that allows the Dex-MA network formation. Optical microscope analysis showed an average diameter of the IPN beads (Ca-Alg/Dex-MA) of 2 mm. This dimension was smaller than that of Ca-Alg beads because of the Dex-MA presence. Moreover, the strength of the IPN beads, and of their corresponding hydrogels, was influenced by the Dex-MA concentration and the crosslinking time. Model proteins (BSA and HRP) were successfully entrapped into the beads and released at a controlled rate, modulated by changing the Dex-MA concentration. The enzymatic activity of HRP released from the beads was maintained. These novel IPN beads have great potential as protein delivery system.

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References

  1. Coviello T, Matricardi P, Marianecci C, Alhaique F. Polysaccharide hydrogels for modified release formulations. J Control Release. 2007;119:5–24.

    Article  CAS  Google Scholar 

  2. Langer R, Peppas N. Chemical and physical structure of polymers as carriers for controlled release of bioactive agents: a review. Polym Rev. 1983;23:61–126.

    Google Scholar 

  3. Pillai O, Panchagnula R. Polymers in drug delivery. Curr Opin Chem Biol. 2001;5:447–51.

    Article  CAS  Google Scholar 

  4. Uhrich KE, Cannizzaro S, Langer R, Shakesheff K. Polymeric systems for controlled drug release. Chem Rev. 1999;99:3181–98.

    Article  CAS  Google Scholar 

  5. Babensee JE, McIntire LV, Mikos AG. Growth factor delivery for tissue engineering. Pharm Res. 2000;17:497–504.

    Article  CAS  Google Scholar 

  6. Baldwin SP, Saltzman WM. Materials for protein delivery in tissue engineering. Adv Drug Deliv Rev. 1998;33:71–86.

    Article  CAS  Google Scholar 

  7. Bilati U, Allémann E, Doelker E. Strategic approaches for overcoming peptide and protein instability within biodegradable nano- and microparticles. Eur J Pharm Biopharm. 2005;59:375–88.

    Article  CAS  Google Scholar 

  8. Frokjaer S, Otzen DE. Protein drug stability: a formulation challenge. Nat Rev Drug Discov. 2005;4:298–306.

    Article  CAS  Google Scholar 

  9. Van De Weert M, et al. Factors of importance for a successful delivery system for proteins. Expert Opin Drug Deliv. 2005;2:1029–37.

    Article  Google Scholar 

  10. Almeida AJ, Souto E. Solid lipid nanoparticles as a drug delivery system for peptides and proteins. Adv Drug Deliv Rev. 2007;59:478–90.

    Article  CAS  Google Scholar 

  11. Couvreur P, Puisieux F. Nano- and microparticles for the delivery of polypeptides and proteins. Adv Drug Deliv Rev. 1993;10:141–62.

    Article  CAS  Google Scholar 

  12. Ye M, Kim S, Park K. Issues in long-term protein delivery using biodegradable microparticles. J Control Release. 2010;146:241–60.

    Article  CAS  Google Scholar 

  13. Backer M, Aloise R, Przekop K, Stoletov K, Backer J. Molecular vehicles for targeted drug delivery. Bioconjugate Chem. 2002;13:462–7.

    Article  CAS  Google Scholar 

  14. Tan M, Choong P, Dass C. Recent developments in liposomes, microparticles and nanoparticles for protein and peptide drug delivery. Peptides. 2010;31:184–93.

    Article  CAS  Google Scholar 

  15. Torchilin VP, Lukyanov AN. Peptide and protein drug delivery to and into tumors: challenges and solutions. Drug Discov Today. 2003;8:259–66.

    Article  CAS  Google Scholar 

  16. Agnihotri S, Mallikarjuna N, Aminabhavi T. Recent advances on chitosan-based micro- and nanoparticles in drug delivery. J Control Release. 2004;100:5–28.

    Article  CAS  Google Scholar 

  17. Kim E, Cho S, Yuk S. Polymeric microspheres composed of pH/temperaturesensitive polymer complex. Biomaterials. 2001;22:2495–9.

    Article  CAS  Google Scholar 

  18. Van Tomme S, Van Nostrum C, Dijkstra M, De Smedt S, Hennink W. Effect of particle size and charge on the network properties of microsphere-based hydrogels. Eur J Pharm Biopharm. 2008;70:522–30.

    Article  Google Scholar 

  19. Zhou SB, Deng XM, Li X. Investigation on a novel core-coated microspheres protein delivery system. J Control Release. 2001;75:27–36.

    Article  CAS  Google Scholar 

  20. Drury JL, Mooney DJ. Hydrogels for tissue engineering: scaffold design variables and applications. Biomaterials. 2003;24:4337–51.

    Article  CAS  Google Scholar 

  21. Hoffman AS. Hydrogels for biomedical applications. Adv Drug Deliv Rev. 2002;54:3–12.

    Article  CAS  Google Scholar 

  22. Peppas NA, et al. Hydrogels in pharmaceutical formulations. Eur J Pharm Biopharm. 2000;50:27–46.

    Article  CAS  Google Scholar 

  23. Hatefi A, Amsden B. Biodegradable injectable in situ forming drug delivery systems. J Control Release. 2002;80:9–28.

    Article  CAS  Google Scholar 

  24. Augst A, Kong H, Mooney D. Alginate hydrogels as biomaterials. Macromol Biosci. 2006;6:623–33.

    Article  CAS  Google Scholar 

  25. Gombotz WR, Wee SF. Protein release from alginate matrices. Adv Drug Deliv Rev. 1998;31:267–85.

    Article  CAS  Google Scholar 

  26. Lee C, Moyer H, Gittens R, Williams J, Boskey A, Boyan B, Schwartz Z. Regulating in vivo calcification of alginate microbeads. Biomaterials. 2010;31:4926–34.

    Article  CAS  Google Scholar 

  27. Matricardi P, Pontoriero M, Coviello T, Casadei M, Alhaique F. In situ cross-linkable novel alginate-dextran methacrylate IPN hydrogels for biomedical applications: mechanical characterization and drug delivery properties. Biomacromolecules. 2008;9:2014–20.

    Article  CAS  Google Scholar 

  28. Bajpai SK, Tankhiwale R. Preparation, characterization and preliminary calcium release study of floating sodium alginate/dextran-based hydrogel beads: part I. Polym Int. 2008;57:57–65.

    Article  CAS  Google Scholar 

  29. Nochos A, Douroumis D, Bouropoulos N. In vitro release of bovine serum albumin from alginate/HPMC hydrogel beads. Carbohydr Polym. 2008;74:451–7.

    Article  CAS  Google Scholar 

  30. DeFail A, Chu C, Izzo N, Marra K. Controlled release of bioactive TGF-[beta]1 from microspheres embedded within biodegradable hydrogels. Biomaterials. 2006;27:1579–85.

    Article  CAS  Google Scholar 

  31. Duvvuri S, Janoria K, Mitra A. Development of a novel formulation containing poly(D,L-lactide-co-glycolide) microspheres dispersed in PLGA-PEG-PLGA gel for sustained delivery of ganciclovir. J Control Release. 2005;108:282–93.

    Article  CAS  Google Scholar 

  32. Fattal E, De Rosa G, Bochot A. Gel and solid matrix systems for the controlled delivery of drug carrier-associated nucleic acids. Int J Pharm. 2004;277:25–30.

    Article  CAS  Google Scholar 

  33. Ungaro F, De Rosa G, Miro A, Quaglia F, La Rotonda M. Microsphere-integrated collagen scaffolds for tissue engineering: effect of microsphere formulation and scaffold properties on protein release kinetics. J Control Release. 2006;113:128–36.

    Article  CAS  Google Scholar 

  34. Lee J, Lee KY. Injectable microsphere/hydrogel combination systems for localized protein delivery. Macromol Biosci. 2009;9:671–6.

    Article  CAS  Google Scholar 

  35. Park H, Temenoff J, Tabata Y, Caplan A, Raphael R, Jansen J, Mikos A. Effect of dual growth factor delivery on chondrogenic differentiation of rabbit marrow mesenchymal stem cells encapsulated in injectable hydrogel composites. J Biomed Mater Res A. 2009;88A:889–97.

    Article  CAS  Google Scholar 

  36. Pescosolido L, Vermonden T, Malda J, Censi R, Dhert W, Alhaique F, Hennink W, Matricardi P. In situ forming IPN hydrogels of calcium alginate and dextran-HEMA for biomedical applications. Acta Biomater. 2011;7:1627–33.

    Article  CAS  Google Scholar 

  37. Pescosolido L, Piro T, Vermonden T, Coviello T, Alhaique F, Hennink W, Matricardi P. Biodegradable IPNs based on oxidized alginate and dextran-HEMA for controlled release of proteins. Carbohydr Polym. 2011;86:208–13.

    Article  CAS  Google Scholar 

  38. Van Dijk-Wolthuis WNE, Kettenes-van den Bosch J, van der Kerk-van Hoof A, Hennink W. Reaction of dextran with glycidyl methacrylate: an unexpected transesterification. Macromolecules. 1997;30:3411–3.

  39. Van Dijk-Wolthuis WNE, Franssen O, Talsma H, van Steenbergen M, den Kettenesvan Bosch J, Hennink W. Synthesis, characterization, and polymerization of glycidyl methacrylate derivatized dextran. Macromolecules. 1995;28:6317–22.

    Article  Google Scholar 

  40. Coviello T, Matricardi P, Balena A, Chiapperino B, Alhaique F. Hydrogels from scleroglucan and ionic crosslinkers: characterization and drug delivery. J Appl Polym Sci. 2010;115:3610–22.

    Article  CAS  Google Scholar 

  41. Grassi M, Lapasin R, Coviello T, Matricardi P, Di Meo C, Alhaique F. Scleroglucan/borax/drug hydrogels: structure characterisation by means of rheological and diffusion experiments. Carbohydr Polym. 2009;78:377–83.

    Article  CAS  Google Scholar 

  42. Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976;72:248–54.

    Article  CAS  Google Scholar 

  43. Rojas-Melgarejo F, Rodriguez-Lopez J, García-Cánovas F, García-Ruiz P. Immobilization of horseradish peroxidase on cinnamic carbohydrate esters. Process Biochem. 2004;39:1455–64.

    Article  CAS  Google Scholar 

  44. La Rotta Hernandez C E. Electroenzymatic oxidation of polyaromatic hydrocarbons using chemical redox mediators in organic media. Electrochem Commun. 2008;10:108–112.

    Google Scholar 

  45. Matricardi P, Di Meo C, Coviello T, Alhaique F. Recent advances and perspectives on coated alginate microspheres for modified drug delivery. Expert Opin Drug Deliv. 2008;5:417–25.

    Article  CAS  Google Scholar 

  46. Pescosolido L, Miatto S, Di Meo C, Cencetti C, Coviello T, Alhaique F, Matricardi P. Injectable and in situ gelling hydrogels for modified protein release. Eur Biophys J. 2010;39:903–9.

    Article  CAS  Google Scholar 

  47. Skjåk-Bræk G, Grasdalen H, Smidsrod O. Inhomogeneous polysaccharide ionic gels. Carbohydr Polym. 1989;10:31–54.

    Article  Google Scholar 

Download references

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Correspondence to Pietro Matricardi.

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D’Arrigo, G., Di Meo, C., Pescosolido, L. et al. Calcium alginate/dextran methacrylate IPN beads as protecting carriers for protein delivery. J Mater Sci: Mater Med 23, 1715–1722 (2012). https://doi.org/10.1007/s10856-012-4644-0

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  • DOI: https://doi.org/10.1007/s10856-012-4644-0

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