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J Photochem Photobiol B. 2020 Jan 7;203:111776. doi: 10.1016/j.jphotobiol.2020.111776. [Epub ahead of print]

Development of thermosensitive hydrogel containing methylene blue for topical antimicrobial photodynamic therapy.

Author information

1
School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong; Department of Life Sciences, Imperial College London, London, UK.
2
School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong.
3
School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong.
4
Institute of Chinese Medicine, State Key Laboratory of Research on Bioactivities and Clinical Applications of Medicinal Plants, The Chinese University of Hong Kong, Hong Kong.
5
Department of Microbiology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong.
6
School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong. Electronic address: sharon.leung@cuhk.edu.hk.

Abstract

Due to the emergence of antibiotic resistance, antimicrobial photodynamic therapy (aPDT) has recently been demonstrated as a promising alternative to antibiotics to treat wound infections caused by multidrug-resistant (MDR) pathogens. This study aimed to evaluate the bacterial killing efficiency of aPDT mediated by methylene blue (MB) loaded thermosensitive hydrogels against methicillin-resistant Staphylococcus aureus (MRSA). Box-Behnken Design method was employed to investigate the impacts of the polymer compositions, Poloxamer 407, Poloxamer 188 and Carbopol 934P, on the gelation temperature (Tsol-gel) and release rate of MB. The viscosity and in vitro bacterial killing efficiency of three selected formulations with Tsol-gel ranged 25-34 °C and MB release in 2 h (the incubation time used for aPDT experiment) ≥ 70%, were assessed. The viscosity was found to increase with increasing P407 content and increasing total gel concentration. In the in vitro aPDT experiment, all tested MB-hydrogels demonstrated >2.5 log10 colony forming unit (CFU) reduction against three clinical relevant MRSA strains. Interestingly, the bacterial reduction increased with decreasing amount of gel added (reduced MB concentration). This was possibly attributed to the increased viscosity at higher gel concentration reducing the diffusion rate of released MB towards bacterial cells leading to reduced aPDT efficiency. In summary, aPDT with the thermosensitive MB hydrogel formulations is a promising treatment strategy for wound infections.

KEYWORDS:

Antibacterial activity; Methicillin resistant Staphylococcus aureus (MRSA); Methylene blue; Multidrug resistance; Skin wound infections; Thermosensitive hydrogel

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