Abstract

Pathogenic bacteria induce subcutaneous infections pose serious threats to global public health. Recently, photodynamic therapy (PDT) has been proposed as a non-invasive approach for anti-microbial treatment without the risk to induce drug resistance. However, due to the hypoxic environment of most anaerobiont-infected sites, the therapeutic efficacy of oxygen consuming PDT has been limited. Herein, a transdermal delivery system is reported to allow effective delivery of photosensitizers into infected skin for PDT treatment of skin infections by bacteria. Considering the overproduction of hydrogen peroxide (H2 O2 ) in the abscess area, catalase (CAT), an enzyme that triggers H2 O2 decomposition to generate O2 , is conjugated with chlorine e6 (Ce6) to form a photosensitizer conjugate (Ce6-CAT) as an enhanced PDT agent against Staphylococcus Aureus. After screening a series of fluorinated low molecular weight polyethylenimine (F-PEI) with different fluorination degrees, the optimized F-PEI formulation is identified with the best transdermal delivery ability system. Upon mixing, the formed Ce6-CAT@F-PEI nanocomplex shows effective transdermal penetration after being applied to the skin surface. With light exposure of the infected skin, highly effective in vivo anti-bacterial PDT therapeutic effect with Ce6-CAT@F-PEI is observed. This work proposes a transdermal PDT therapeutic nanomedicine particularly promising for the anti-bacterial treatment of skin infections.

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