Increase in the Vascular Residence Time of Propranolol-Loaded Nanoparticles Coated with Heparin

Abstract

Propranolol-HCI incorporated nanoparticles prepared with a blend of a polyester and a polycationic polymer and coated or not with a low molecular weight heparin by electrostatic interactions were prepared by emulsification followed by solvent evaporation. The mean diameter was 388 and 357 nm for coated and uncoated nanoparticles, respectively, and the entrapment efficiency ranged from 20 to 32%. Coated nanoparticles were negatively-charged, whereas uncoated nanoparticles displayed a positive zeta potential (+30 mV). After intravenous administration to rabbits of propranolol-HCI solution and propranolol-loaded nanoparticles coated or not with heparin, pharmacokinetic data revealed that coated nanoparticles exhibited a prolonged blood residence time. It can be concluded that the hydrophilic layer of heparin at the surface of nanoparticles conferred stealth properties which probably reduce the phagocytosis process and avoid immediate uptake by the mononuclear phagocytic system.

Heparin‐Engineered Mesoporous Iron Metal‐Organic Framework Nanoparticles: Toward Stealth Drug Nanocarriers

“…Although the heparin coating approach has been previously reported for preventing from the rapid macrophage uptake for different classes of NPs, [33][34][35][36] to the best of our knowledge, this is the fi rst time that the surface heparin-engineering of MOFs is reported, providing them with remarkable potential stealth properties.…”

Protein source and choice of anticoagulant decisively affect nanoparticle protein corona and cellular uptake

“…Accordingly, several manuscripts report a prolonged blood circulation of nanoparticles coated with heparin. [33][34][35] Furthermore, heparin has proven its ability to inhibit the adsorption and the internalization of nanoparticles by a murine macrophage-like cell line in vitro. 36 On the other hand, a high uptake of heparin-based nanocapsules into different tumor cell lines was described, 37 as well as an enhanced uptake of heparin functionalized PLGAbased nanoparticles into a fibroblast and tumor cell line.…”

Stealth nanoparticles coated with heparin as peptide or protein carriers

“…In another report, the half-life in plasma of the methoxy poly(ethylene glycol)poly(d,l-lactic acid) block copolymers (MePEG-PLA) nanoparticles administered intravenously to rats was increased by a factor 180 compared with conventional PLA nanoparticles . In a previous study, the experimental half-life of propranolol-HCl was increased 18-fold by encapsulation in Stealth nanoparticles coated with LMWH (Socha et al, 2008). Many authors have demonstrated and confirmed the Stealth properties of particles coated by PEG (Awasthi et al, 2003;Béduneau et al, 2006).…”

“…In a previous study, we developed a new system of Stealth nanoparticles (Socha et al, 2008). In contrast to many authors who covalently bound hydrophilic molecules to polymers during nanoparticles preparation (Gaur et al, 2000;Labarre et al, 2005), we prepared Stealth nanoparticles based on electrostatic interactions between quaternary ammonium groups of a polycationic polymer and the sulfate and carboxylate groups of a low molecular weight heparin (LMWH).…”