Hyaluronic acid-coated bovine serum albumin nanoparticles loaded with brucine as selective nanovectors for intra-articular injection

Int J Nanomedicine. 2013:8:3843-53. doi: 10.2147/IJN.S50721. Epub 2013 Oct 7.

Abstract

Objective: To evaluate the potential of hyaluronic acid (HA)-coated bovine serum albumin nanoparticles (BSANPs) as a novel chondrocyte-targeting drug-delivery nanomedicine.

Methods: The HA-BSANPs were characterized by dynamic light scattering, transmission electron microscopy, differential scanning calorimetry, and X-ray diffraction. Fluorescence imaging was used to visualize the distribution of nanoparticles after intra-articular injection. The chondrocyte-targeting efficiency and cellular uptake mechanism of HA-BSANPs were investigated using endocytic inhibitors.

Results: HA-BSANPs were successfully prepared with HA coating the surface and amorphous drug in the core. Compared with BSANPs, HA-BSANPs exhibited improved uptake by chondrocytes through a receptor-mediated active uptake mechanism. The endocytosis process of BSANPs and HA-BSANPs involved clathrin-mediated endocytosis, caveolae-mediated endocytosis, and macropinocytosis. No apparent thickening or hyperplasia of the synovium was observed in either BSANPs or HA-BSANPs. The HA-BSANPs could reside in the articular cavity of rats for more than 14 days, which was significantly longer than BSANPs.

Conclusion: HA-BSANPs are a promising carrier for articular-related diseases due to elongated articular residence and improved chondrocytic accumulation.

Keywords: BSA; chondrocyte; hyaluronic acid; intra-articular injection; nanoparticles.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Adjuvants, Immunologic / pharmacokinetics
  • Animals
  • Cells, Cultured / drug effects
  • Cells, Cultured / metabolism*
  • Chondrocytes / drug effects
  • Chondrocytes / metabolism*
  • Hyaluronic Acid / chemistry
  • Hyaluronic Acid / pharmacokinetics*
  • Injections, Intra-Articular
  • Joints / drug effects
  • Joints / metabolism
  • Male
  • Nanocapsules / administration & dosage
  • Nanocapsules / chemistry*
  • Nanocapsules / ultrastructure
  • Rabbits
  • Rats, Sprague-Dawley
  • Serum Albumin, Bovine / chemistry*
  • Strychnine / administration & dosage
  • Strychnine / analogs & derivatives*
  • Strychnine / pharmacokinetics
  • Tissue Distribution

Substances

  • Adjuvants, Immunologic
  • Nanocapsules
  • Serum Albumin, Bovine
  • brucine
  • Hyaluronic Acid
  • Strychnine