Chitosan in the therapy against diabetic ulcers

Around one third of all type-2 diabetes sufferers develop diabetic foot ulcers in the course of their disease. Due to biofilm formation and multi-resistant bacteria, inflammation occurs in 50% of those affected. This article presents a study investigating the treatment of these with chitosan-containing metallic nanoparticles coupled to toluidine blue as a photosensitizer.

A NANO PHOTOTHERANOSTIC APPROACH OF TOLUIDINE BLUE CONJUGATED GOLD SILVER CORE SHELLS MEDIATED PHOTODYNAMIC THERAPY TO TREAT DIABETIC FOOT ULCER

Akhtar, F., Khan, A.U., Qazi, B., Kulanthaivel, S., Mishra, P., Akhtar, K., & Ali, A. (2021). A nano phototheranostic approach of toluidine blue conjugated gold silver core shells mediated photodynamic therapy to treat diabetic foot ulcer. Scientific Reports, 11.

Type-2 diabetes affects 90 to 95% of all diabetes cases and has become a health problem. Immunocompromised patients in particular often suffer from non-healing wounds. In addition, one-third of all diabetes type-2 affected develop foot ulcers (diabetic foot infections (DFIs)) during the progress of the disease, 50% of them become infected. This leads to a severe reduction in the quality of life of those affected due to an increase in morbidity, mortality and the risk of lower extremity amputations.
Biofilms are responsible for the inflammation in 65% of cases. Especially S. aureus and P. aeruginosa lead to DFIs. Due to the formation of biofilms, treatment with antibiotics is difficult. Furthermore, infections with multi-resistant bacteria are also increasing. Metallic nanoparticles can offer an alternative. These are able to eliminate pathogens by binding to the cell membrane or by the formation of radical oxygen species. In addition, dyes such as toluidine blue O (TBO) can also be used as antibacterial photosensitizers.
For the reason, in the presented study, chitosan-coated gold nanoparticles (TBO-chit-Au-AgNPs) with silver coat coupled to TBO were investigated as a therapy for the treatment of diabetic foot ulcers. In addition to the success of coupling, cytotoxicity and antimicrobial effect on mono- and polymicrobial biofilms, the efficacy of TBO-chit-Au-AgNPs against DFIs was also investigated in vivo in diabetic rats.

RESULTS

• Detection of successfully synthesized TBO-chit-Au-AgNPs by UV-spectrometry and transmission electron microscopy.
• No detection of impurities and aggregations of the particles
• Strong zeta potential indicates good stability and biocompatibility
• No observation of cytotoxic effects with or without laser irradiation presumably due to biological and chemical properties of the chitosan
• Reduction of bacterial density when applied to mono- and polymicrobial biofilms
• Monomicrobial biofilms more reduced upon exposure than polymicrobial biofilms
• In vivo: healing of DFI in rats within 7 days with daily treatment
• Reduced levels of IL-6 and TNF-α compared to untreated group, indicating restoration of immune suppression

Summary: This study found that the use of TBO-chit-Au-AgNPs reduced the density of mono- and polymicrobial S. aureus and P. aeruginosa biofilms. Especially for monomicrobial biofilms, the effect was thereby enhanced by excitation of TBO by laser. In addition, no cytotoxic properties were observed in vitro. In vivo, the application of TBO-chit-Au-AgNPs resulted in a reduction of inflammatory markers, as well as healing of DFI within 7 days with daily treatment. Overall, this makes TBO-chit-Au-AgNPs a promising antibacterial approach to treat diabetic foot ulcers.