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Biodegradable and redox-responsive chitosan/poly(l-aspartic acid) submicron capsules for transmucosal delivery of proteins and peptides

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Abstract

The development of peptides and proteins is hampered by their rapid clearance in liver and other body tissues by proteolytic enzymes, so these drugs are difficult to administer except for the injection. Here, we designed and fabricated a novel biodegradable and redox-responsive submicron capsules through the layer-by-layer technique with poly(l-aspartic acid) and chitosan for transmucosal delivery of proteins and peptides. TEM graphs reveal that the intact submicron capsules were obtained and the shell of submicron capsules was about 40 nm. The mucoadhesion test indicates that the adsorption amount of the mucin could achieve up to 96.2 μg per 2 mg. The cell viability test shows that all types of submicron capsules had good cytocompatibility and the cell viability was above 90 %. As a drug model, the insulin could be loaded in the submicron capsules, and the loading efficiency was about 5 %. The release amount of insulin could be regulated by the levels of GSH. Therefore, the mucoadhesive submicron capsules as vehicles have a potential for the mucosal delivery (e.g. nasal and buccal) of therapeutic peptide and protein drugs.

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References

  1. Alles N, Soysa NS, Hussain MDA, Tomomatsu N, Saito H, Baron R, et al. Polysaccharide nanogel delivery of a TNF-α and RANKL antagonist peptide allows systemic prevention of bone loss. Eur J Pharm Sci. 2009;37:83–8.

    Article  CAS  Google Scholar 

  2. Toita S, Sawada S, Akiyoshi K. Polysaccharide nanogel gene delivery system with endosome-esca** function: co-delivery of plasmid DNA and phospholipase A2. J Control Release. 2011;155:54–9.

    Article  CAS  Google Scholar 

  3. Shah PP, Desai PR, Patel AR, Singh MS. Skin permeating nanogel for the cutaneous co-delivery of two anti-inflamatory drugs. Biomaterials. 2012;33:1607–17.

    Article  CAS  Google Scholar 

  4. Cohen S, Coué G, Beno D, Korenstein R, Engbersen JFJ. Bioreducible poly(amidoamine)s as carriers for intracellular protein delivery to intestinal cells. Biomaterials. 2012;33:614–23.

    Article  CAS  Google Scholar 

  5. Cheng C, Zhang XG, **ang JX, Wang YX, Zheng C, Lu ZT, et al. Development of novel self-assembled poly(3-acrylamidophenylboronic acid)/poly(2-lactobionamidoethyl methacrylate) hybrid nanoparticles for improving nasal adsorption of insulin. Soft Matter. 2012;8:765–73.

    Article  CAS  Google Scholar 

  6. Haložan D, Déjugnat C, Brumen M, Sukhorukov GB. Entrapment of a weak polyanion and H+/Na+ exchange in confined polyelectrolyte microcapsules. J Chem Inf Model. 2005;45:1589–92.

    Article  Google Scholar 

  7. Yu L, Gao YG, Yue XL, Liu SQ, Dai ZF. Novel hollow microcapsules based on iron-heparin complex multilayers. Langmuir. 2008;24:13723–9.

    Article  CAS  Google Scholar 

  8. Peng CY, Zhao QH, Gao CY. Sustained delivery of doxorubicin by porous CaCO3 and chitosan/alginate multilayers-coated CaCO3 microparticles. Colloid Surf A. 2010;353:132–9.

    Article  CAS  Google Scholar 

  9. Wang ZP, Feng ZQ, Gao CY. Stepwise assembly of the same polyelectrolytes using host-guest interaction to obtain microcapsules with multiresponsive properties. Chem Mater. 2008;20:4194–9.

    Article  CAS  Google Scholar 

  10. Kozlovskaya V, Kharlampieva E, Chang SH, Muhlbauer R, Tsukruk VV. pH-Responsive layered hydrogel microcapsules as gold nanoreactors. Chem Mater. 2009;21:2158–67.

    Article  CAS  Google Scholar 

  11. Kozlovskaya V, Sukhishvili SA. pH-Controlled permeability of layered hydrogen–bonded polymer capsules. Macromolecules. 2006;39:5569–72.

    Article  CAS  Google Scholar 

  12. Kinnane CR, Wark K, Such GK, Johnston APR, Caruso F. Peptide-functionalized, low-biofouling click multilayers for promoting cell adhesion and growth. Small. 2009;5:444–8.

    Article  CAS  Google Scholar 

  13. Zelikin AN, Quinn F, Caruso F. Disulfide cross-linked polymer capsules: en route to biodeconstructible systems. Biomacromolecules. 2006;7:27–30.

    Article  CAS  Google Scholar 

  14. Connal LA, Kinnane CR, Zelikin AN, Caruso F. Stabilization and functionalization of polymer multilayers and capsules via thiol-ene click chemistry. Chem Mater. 2009;21:576–8.

    Article  CAS  Google Scholar 

  15. Chong SF, Chandrawati R, Stadler B, Park J, Cho JH, Wang YJ, et al. Stabilization of polymer-hydrogel capsules via thiol-disulfide exchange. Small. 2009;22:2601–10.

    Article  Google Scholar 

  16. Zhou J, Romero G, Rojas E, Ma L, Moya S, Gao CY. Layer-by-layer chitosan/alginate coatings on poly(lactide-co-glycolide) nanoparticles for antifouling protection and Folic acid binding to achieve selective cell targeting. J Colloid Interface Sci. 2010;345:241–7.

    Article  CAS  Google Scholar 

  17. Francis Suh JK, Matthew HWT. Application of chitosan-based polysaccharide biomaterials in cartilage tissue engineering: a review. Biomaterials. 2000;21:2589–98.

    Article  CAS  Google Scholar 

  18. Cheng R, Feng F, Meng F, Deng C, Feijen J, Zhong Z. Glutathione-responsive nano-vehicles as a promising platform for targeted intracellular drug and gene delivery. J Control Release. 2011;152:2–12.

    Article  CAS  Google Scholar 

  19. Tomida M, Nakato T, Matsunami S, Kakuchi T. Convenient synthesis of high molecular weight poly (succinimide) by acid-catalyses polycondensation of l-asparticacid. Polymer. 1997;38:4733–6.

    Article  CAS  Google Scholar 

  20. Shu SJ, Zhang XG, Teng DY, Wang Z, Li CX. Polyelectrolyte nanoparticles based on water-soluble chitosan-poly(l-aspartic acid)-polyethylene glycol for controlled protein release. Carbohyd Res. 2009;344:1197–204.

    Article  CAS  Google Scholar 

  21. Krauland AH, Hoffer MH, Bernkop-Schnürch A. Viscoelastic preoerties of a new in situ gelling thiolated chitosan conjugate. Drug Dev Ind Pharm. 2005;31:885–93.

    Article  CAS  Google Scholar 

  22. Wang X, Zheng C, Wu ZM, Teng DY, Zhang XG, Wang Z. Chitosan-NAC nanoparticles as a vehicle for nasal absorption enhancement of insulin. J Biomed Mater Res B. 2009;88B:150–61.

    Article  CAS  Google Scholar 

  23. Stober W, Fink A, Bohn E. Controlled growth of monodisperse silica spheres in the micron size range. J Colloid Interface Sci. 1968;26:62–9.

    Article  Google Scholar 

  24. Shu SJ, Sun CY, Zhang XG, Wu ZM, Wang Z, Li CX. Hollow and degradable polyelectrolyte nanocapsules for protein drug delivery. Acta Biomater. 2010;6:210–7.

    Article  CAS  Google Scholar 

  25. Shu SJ, Wang X, Zhang XG, Zhang XJ, Wang Z, Li CX. Disulfide cross-linked biodegradable polyelectrolyte nanoparticles for the oral delivery of protein drugs. New J Chem. 2009;33:1882–7.

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  27. He P, Davis SS, Illum L. In vitro evaluation of the mucoadhesive properties of chitosan microspheres. Int J Pharm. 1998;166:75–88.

    Article  CAS  Google Scholar 

  28. Yin LC, Ding JY, He CB, Cui LM, Tang C, Yin CH. Drug permeability and mucoadhesion properties of thiolated trimethyl chitosan nanoparticles in oral insulin delivery. Biomaterials. 2009;30:5691–700.

    Article  CAS  Google Scholar 

  29. Schipper NGM, Varum KM, Artursson P. Chitosans as absorption enhancers for poorly absorbable arugs. 1: influence of molecular weight and degree of acetylation on drug transport across human intestinal epithelial (Caco-2) cells. Pharm Res. 1996;13:1686–92.

    Article  CAS  Google Scholar 

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (Grant No. 20804021 and 21174071).

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Authors and Affiliations

  1. The Key Laboratory of Functional Polymer Materials of Ministry Education, Institute of Polymer Chemistry, Nankai University, Tian**, 300071, China

    C. Zheng, X. G. Zhang, L. Sun, Z. P. Zhang & C. X. Li

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  1. C. Zheng
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  2. X. G. Zhang
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  3. L. Sun
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  4. Z. P. Zhang
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  5. C. X. Li
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Correspondence to X. G. Zhang or C. X. Li.

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Zheng, C., Zhang, X.G., Sun, L. et al. Biodegradable and redox-responsive chitosan/poly(l-aspartic acid) submicron capsules for transmucosal delivery of proteins and peptides. J Mater Sci: Mater Med 24, 931–939 (2013). https://doi.org/10.1007/s10856-013-4863-z

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  • DOI: https://doi.org/10.1007/s10856-013-4863-z

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