Insight into the fabrication of polymeric particle based oxygen carriers

Abstract

For the sake of protein stability and targeted application as blood substitutes, formulation customization of hemoglobin-loaded polymeric particles (HbP) was conducted via a double emulsion method. Screening of the emulsification parameters was firstly performed for the stability of Hb, and the structure and functions of recovered Hb could be well preserved via CD and UV-vis spectroscopy investigation. In the optimized conditions, Hb was loaded into the polymeric matrix formed of three material compositions. They were poly(ϵ-caprolactone)(PCL), poly(ethylene glycol)-block-poly(allyl glycidyl ether) (functionalized with mercaptopropionic acid)-block-poly(ϵ-caprolactone) (PEG-PAGE(MPA)-PCL), and the blend of the two polymers. The morphology, internal structure, in vitro leakage and hemocompatibility of the HbP products were characterized in detail, and the encapsulation mechanism was explored by the combined analysis of the encapsulation efficiency, non-specific protein adsorption and in vitro leakage studies. Results showed that the burst release effect found in homopolymers could be alleviated by use of block copolymers due to the reduced protein adsorption, and completely avoided by further cross-linking of particles through carbonyl-amino condensation reactions. The amphiphilic copolymers showed relatively high stability in blood and no interference with blood components compared with hydrophobic PCL. These results suggest that both the optimization of emulsion formation and material composition are prerequisite for stable formulations of Hb encapsulated in polymeric particles.

Keywords: Blood compatibility; Burst release; Cross-linking; Emulsification; Hemoglobin; Polymeric particle.