High-performance reoxygenation from PLGA-PEG/PFOB emulsions: a feedback relationship between ROS and HIF-1α

Abstract

Jie Wang,1,* Ruochen Wang,1,* Niannian Li,1 Xi Shen,2 Gang Huang,3 Jun Zhu,1,4 Dannong He1,4 1School of Materials Science and Engineering, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 2The Department of Ophthalmology, Ruijin Hospital, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 3Shanghai University of Medicine and Health Sciences, Shanghai, People’s Republic of China; 4National Engineering Research Center for Nanotechnology, Shanghai, People’s Republic of China *These authors contributed equally to this work Background: Hypoxemia is one of the most common pathological processes in various clinical diseases. Methods: A novel emulsion of poly(lactide-co-glycolide)-poly(ethylene glycol)/perfluorooctyl bromide has been developed to improve arterial hypoxemia through pulmonary drug delivery. Hypoxia-reoxygenation experiment was used to investigate the ability of the emulsion to supply oxygen and the saline lavage acute lung injury model was established to evaluate oxygen supply of the emulsion. Results: It has been demonstrated that an apparent increase has been detected in the cytotoxicity test of the emulsion, indicating its lower cell toxicity. A hypoxia-reoxygenation experiment uncovered the fact that notable cell growth was observed after reoxygenation with poly(lactide-co-glycolide)-poly(ethylene glycol)/perfluorooctyl bromide emulsion because of the ability of the emulsion to supply oxygen adequately and reasonably. Moreover, the level of intracellular reactive oxygen species was significantly enhanced during hypoxia, which further influenced the concentration and activity of hypoxia-inducible factor-1α (HIF-1α). Furthermore, the upregulated expression of HIF-1α during hypoxia has verified that certain emulsions can increase HIF-1α content and relieve hypoxia, which further indicates HIF-1α plays an essential role in improving cell viability. Afterwards, the saline lavage acute lung injury model was established to evaluate oxygen supply of the emulsion and the result shows considerable improvement of lung ventilation of rabbits. Conclusion: We recommend that the feedback relationship between reactive oxygen species and HIF-1 plays an essential role in improving cell viability. It is anticipated that the emulsion will be applied in the field of alleviating hypoxemia. Keywords: perfluorocarbon, oxygen concentration, hypoxia-reoxygenation, reactive oxygen species, hypoxia-inducible factor-1α, lung ventilation

Keywords

• Perfluorocarbon
• oxygen concentration
• hypoxia-reoxygenation
• reactive oxygen species
• hypoxia-inducible factor-1α
• lung ventilation