Insight into the fabrication of polymeric particle based oxygen carriers.
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.
State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China; University of Chinese Academy of Sciences, Beijing 100049, China.
Bin
B
Li
State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China; University of Chinese Academy of Sciences, Beijing 100049, China.
Shasha
S
He
State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China.
Yanxin
Y
Qi
State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China.
Zhigang
Z
Xie
Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China.
Xuesi
X
Chen
State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China.
Xiabin
X
Jing
State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China. Electronic address: ybhuang@ciac.ac.cn.
Yubin
Y
Huang
D000818:Animals; D001672:Biocompatible Materials; D002626:Chemistry, Pharmaceutical; D002942:Circular Dichroism; D003432:Cross-Linking Reagents / Q000737:chemistry; D004355:Drug Stability; D004655:Emulsions; D006454:Hemoglobins / Q000737:chemistry* / Q000378:metabolism; D057927:Hydrophobic and Hydrophilic Interactions; D036103:Nanotechnology; D010100:Oxygen / Q000097:blood / Q000737:chemistry*; D010952:Plasma Substitutes / Q000138:chemical synthesis* / Q000378:metabolism; D011091:Polyesters / Q000138:chemical synthesis; D011092:Polyethylene Glycols / Q000138:chemical synthesis; D011108:Polymers / Q000138:chemical synthesis* / Q000378:metabolism; D011487:Protein Conformation; D055550:Protein Stability; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D012997:Solvents / Q000737:chemistry; D013056:Spectrophotometry, Ultraviolet; D013678:Technology, Pharmaceutical / Q000379:methods
D001672:Biocompatible Materials; D003432:Cross-Linking Reagents; D004655:Emulsions; D006454:Hemoglobins; D010952:Plasma Substitutes; D011091:Polyesters; D011108:Polymers; D012997:Solvents; C016240:polycaprolactone; D011092:Polyethylene Glycols; D010100:Oxygen
Blood compatibility; Burst release; Cross-linking; Emulsification; Hemoglobin; Polymeric particle