Stealth nanoparticles coated with heparin as peptide or protein carriers

Abstract

Nanoparticles (prepared from a mixture of polyester and a polycationic polymer) loaded with insulin were prepared by a double emulsion method followed by evaporation solvent. Low molecular weight heparin (LMWH) was bound by electrostatic interactions onto the surface of the particles to confer Stealth properties. These nanoparticles were characterized in vitro (mean diameter, zeta potential, encapsulation efficiency, and release kinetics) and compared with conventional (without LMWH) and unloaded nanoparticles. The pharmacokinetics of insulin were studied after intravenous injection into diabetic rats in the form of Stealth or conventional nanoparticles or as a solution. Stealth nanoparticles allowed an increase in the elimination half-life of insulin, showing that the hydrophilic layer of LMWH was able to limit recognition by the mononuclear phagocytosis system in vivo. However, complement activation studies (CH50) did not reveal significant difference between Stealth and conventional nanoparticles.

Keywords::

• Nanoparticles
• stealth
• protein
• heparin
• eudragit
• poly-ϵ-caprolactone
• CH50

Acknowledgments

The authors would like to thank Professor Jean-Michel Cardot from the school of pharmacy of Clermont-Ferrand for help with pharmacokinetic parameter calculation. The authors wish to thank Doctor Gillian Barratt from the school of pharmacy of Châtenay-Malabry-Paris XI for her great help in revising the manuscript.

Declaration of interest: The authors report no conflicts of interest.