Lipid bilayer-coated mesoporous silica nanoparticles carrying bovine hemoglobin towards an erythrocyte mimic

Int J Pharm. 2018 May 30;543(1-2):169-178. doi: 10.1016/j.ijpharm.2018.03.037. Epub 2018 Mar 19.

Abstract

Hemoglobin (Hb)-loaded mesoporous silica nanoparticles (MSNs) coated with a lipid bilayer (LB-MSNs) were investigated as an erythrocyte mimic. MSNs with a large average pore size (10 nm) act as a rigid core and provide a protective environment for Hb encapsulated inside the pores. The colloidal stability of Hb-loaded MSNs was enhanced upon the application of a lipid bilayer, through fusion of PEGylated liposomes onto the exterior surface of Hb-loaded MSNs. The morphology and mesostructure of the MSNs were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM) and surface area analysis. The Hb loading capacity (mg/g) in MSNs was studied by thermogravimetric analysis (TGA). UV-Vis absorption spectroscopy revealed that Hb inside MSNs had an identical, but slightly broadened peak in the Soret region compared to free Hb. Furthermore the encapsulated Hb exhibits similar peroxidase-like activity in catalyzing the oxidation of 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) with hydrogen peroxide. The introduction of a supported lipid bilayer (LB) demonstrated the potential to prevent premature Hb release (the burst release decreased from 25.50 ± 0.33% to 6.73 ± 0.83%) and increased the colloidal stability of the Hb-loaded MSNs (hydrodynamic diameter remained ∼250 nm for at least one week). The in vivo systemic circulation and biodistribution of LB-MSNs were studied in optically transparent zebrafish embryos, revealing that LB-MSNs have the potential to act as an erythrocyte mimic in transfusion therapy.

Keywords: Erythrocyte mimic; Hemoglobin; Lipid bilayer; Mesoporous silica nanoparticles; Zebrafish embryos.

MeSH terms

  • Animals
  • Animals, Genetically Modified / metabolism
  • Blood Circulation
  • Cattle
  • Drug Liberation
  • Embryo, Nonmammalian / metabolism
  • Erythrocytes
  • Hemoglobins / administration & dosage*
  • Hemoglobins / chemistry
  • Lipid Bilayers / administration & dosage*
  • Lipid Bilayers / chemistry
  • Nanoparticles / administration & dosage*
  • Nanoparticles / chemistry
  • Porosity
  • Silicon Dioxide / administration & dosage*
  • Silicon Dioxide / chemistry
  • Zebrafish / embryology
  • Zebrafish / genetics
  • Zebrafish / metabolism

Substances

  • Hemoglobins
  • Lipid Bilayers
  • Silicon Dioxide