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  2. Evaluation of hypocrellin A-loaded lipase sensitive polymer micelles for intervening methicillin-resistant Staphylococcus Aureus antibiotic-resistant bacterial infection

Evaluation of hypocrellin A-loaded lipase sensitive polymer micelles for intervening methicillin-resistant Staphylococcus Aureus antibiotic-resistant bacterial infection

  • Mater Sci Eng C Mater Biol Appl. 2020 Jan:106:110230. doi: 10.1016/j.msec.2019.110230.
Ling-Yuan Guo 1 Shu-Zhen Yan 1 Xin Tao 1 Qing Yang 2 Qiang Li 1 Tian-Shu Wang 1 Shu-Qin Yu 3 Shuang-Lin Chen 4
Affiliations

Affiliations

  • 1 Jiangsu Province Key Laboratory for Microbes and Functional Genomics, College of Life Sciences, Nanjing Normal University, Nanjing, 210023, China.
  • 2 State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 31003, China.
  • 3 College of Life Sciences, Nanjing Normal University, Nanjing, 210023, China. Electronic address: yushuqin@njnu.edu.cn.
  • 4 Jiangsu Province Key Laboratory for Microbes and Functional Genomics, College of Life Sciences, Nanjing Normal University, Nanjing, 210023, China. Electronic address: chenshuanglin@njnu.edu.cn.
Abstract

There is an urgent need for new Antibacterial strategies to overcome the emergence of Antibiotic resistance. Antibacterial photodynamic therapy (APDT) may be an effective method to deliver photosensitizers for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections. Here, we report that the photosensitizer hypocrellin A (HA) loaded into lipase-sensitive methoxy poly (ethylene glycol)-block-poly(ε-caprolactone) (mPEG-PCL) micelles showed high anti-MRSA activity in vitro and in vivo by PDT. Once the micelles come into contact with bacteria that secrete Lipase, the PCL is degraded to release HA. Our results showed that the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of mPEG-PCL/HA micelles after light irradiation were 0.69 and 1.38 mg/L (HA concentration), respectively. In the dark, the MIC and MBC of the micelles were 250 and 500 mg/L (HA concentration), respectively. The fluorescent stain results further demonstrated the photodynamic Antibacterial activity of mPEG-PCL/HA micelles. The survival rate of mice subjected to experimental acute peritonitis increased to 86% after treated with the micelles. The polymeric micelles showed low hemolytic activity and biocompatibility, simultaneously preventing aggregation in vivo and enhancing the water solubility of HA. Thus, the photosensitizer HA loaded micelles could be used as APDT for infections caused by bacteria without Antibiotic resistance.

Keywords

Antimicrobial photodynamic therapy; Drug resistance infections; Hypocrellin A; Lipase sensitivity; Polymeric micelle.

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