Encapsulation of hemoglobin within mPEG-b-PCL micelle for development of artificial oxygen carrier

Abstract

The aim of this study is to develop hemoglobin (hb) encapsulated self-assembled polymer for use as artificial oxygen carrier. Methoxy-polyethylene glycol (mPEG₄₅) block and poly (ɛ-caprolactone [ɛ-CL]) (mPEG-b-PCL) that formed diblock copolymer was synthesized via ring-opening polymerization (ROP). Extracted and purified hb was then encapsulated in polymer with critical micelle concentration (CMC) at 1.0–2.0 mg/mL. Average encapsulation efficiency of the human hb-micelle was 45 ± 5% as compared to 66.7 ± 15% of bovine hb-micelle. The derived half-life of hb encapsulated micelle was 112,242 ± 40 min upon atmospheric air exposure as compared to 30 ± 10 min of the experiment control (free hb). Results of oxygen reversibility study also demonstrated the capability of hb-micelle to endure minimum average of six oxygenation and deoxygenation cycles as compared to an average less than one average cycle by the control. Control (free bovine and human hb) and treated cell (bovine and human hb-micelle) were incubated for 48 h and analyzed every 4, 8, 12, 16, 24, and 48 h. Cell viability assay on macrophage cell demonstrated both free hb(s) recorded decreasing cell growths as early as 8 h as compared to the increasing cell viability pattern by the encapsulated hb(s) indicating lesser cytotoxicity. 

Graphical Abstract

Keywords:

• Artificial oxygen carrier
• blood substitute
• diblock copolymer
• hemoglobin
• micelle

Ethical approval

USM/JEPeM/16110533.

Additional information

Funding

The authors wish to acknowledge Ministry of Education Malaysia for funding the research under Fundamental Research Grant Scheme [FRGS/1/2019/STG07/USM/02/13] and Universiti Sains Malaysia (USM) for sponsoring this project under USM short-term grant [304/CIPPT/63123311] and Advanced Medical and Dental Institute for technical support.