Hybrid Alginate-Protein-Coated Graphene Oxide Microcapsules Enhance the Functionality of Erythropoietin Secreting C2C12 Myoblasts

Mol Pharm. 2017 Mar 6;14(3):885-898. doi: 10.1021/acs.molpharmaceut.6b01078. Epub 2017 Feb 16.


The beneficial effect of combining alginate hydrogel with graphene oxide (GO) on microencapsulated C2C12-myoblast viability has recently been described. However, the commercially available GO lacks homogeneity in size, this parameter being of high relevance for the cell fate in two-dimensional studies. In three-dimensional applications the capacity of this material for binding different kinds of proteins can result in the reduction of de novo released protein that can effectively reach the vicinity of the microcapsules. Undoubtedly, this could be an important hurdle in its clinical use when combined with alginate-PLL microcapsules. Here, we demonstrate that the homogenization of GO nanoparticles is not a mandatory preparation step in order to get the best of this material upon cell microencapsulation. In fact, when the superficial area of these particles is increased, higher amounts of the therapeutic protein erythropoietin (EPO) are adsorbed on their surface. On the other hand, we have been able to improve even more the favorable effects of this graphene derivative on microencapsulated cell viability by forming a protein biocorona. These proteins block the potential binding sites of EPO and, therefore, enhance the amount of therapeutic drug that is released. Finally, we prove that these hybrid alginate-protein-coated GO-microcapsules are functional in vivo.

Keywords: albumin; alginate; cell microencapsulation; fetal bovine serum; graphene oxide.

MeSH terms

  • Alginates / chemistry*
  • Animals
  • Capsules / chemistry
  • Capsules / pharmacology*
  • Cell Line
  • Cell Survival / drug effects
  • Drug Compounding / methods
  • Erythropoietin / metabolism*
  • Glucuronic Acid / chemistry
  • Graphite / chemistry
  • Graphite / pharmacology*
  • Hexuronic Acids / chemistry
  • Hydrogel, Polyethylene Glycol Dimethacrylate / chemistry
  • Hydrogel, Polyethylene Glycol Dimethacrylate / pharmacology
  • Mice
  • Mice, Inbred C3H
  • Myoblasts / drug effects*
  • Myoblasts / metabolism
  • Nanoparticles / chemistry
  • Oxides / chemistry
  • Oxides / pharmacology*
  • Proteins / chemistry*


  • Alginates
  • Capsules
  • Hexuronic Acids
  • Oxides
  • Proteins
  • Erythropoietin
  • Hydrogel, Polyethylene Glycol Dimethacrylate
  • Graphite
  • Glucuronic Acid