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Formulation and characterisation of lyophilised curcumin solid dispersions for antimicrobial photodynamic therapy (aPDT)

 

Introduction: Curcumin is currently under investigation as a potential photosensitiser in antimicrobial photodynamic therapy (aPDT). Previous studies have demonstrated high phototoxicity towards Gram-positive (G+) bacteria, but lower effect on Gram-negative (G-) bacteria.

Aims and objectives: The purpose of this study was to develop rapidly dissolving formulations of curcumin for photoinactivation of G+ and G- bacteria. Complete photoinactivation after exposure to less than 10 µM curcumin and a light dose (emission maximum: 450 nm) below 30 J/cm² was aimed for.

Materials and methods: Curcumin solid dispersions with methyl-β-cyclodextrin and hyaluronic acid (HA), hydroxypropyl methylcellulose (HPMC) or both HA and HPMC were prepared through lyophilisation. The lyophilisates were characterised by curcumin drug load (% (w/w)), differential scanning calorimetry and by in vitro photoinactivation of a model G+ and G- bacterium.

Results: The drug load in the lyophilisates was primarily dependent on the selected ratio between curcumin and the cyclodextrin.  The selected type of polymer also affected the drug load as well as the dissolution properties. The highest drug load detected was approximately 5% (w/w) in optimised formulations. These optimised lyophilisates induced a > log 6 reduction of colony forming units/ml after exposure down to 0.5 µM curcumin and a light dose down to 11 J/cm².

Conclusion: The high drug load combined with high phototoxicity towards G+ and G- bacteria make these rapidly dissolving curcumin lyophilisates suitable for in vivo aPDT. aPDT with optimised curcumin formulations should be explored as an alternative to topical antibiotics in treatment of infections.

Authors: Kristine Opsvik Wikene1, Anne Bee Hegge1, Ellen Bruzell2, Hanne Hjorth Tønnesen1.
Affiliations: 1University of Oslo, School of Pharmacy, Department of Pharmaceutics, Norway, and 2 Nordic Institute of Dental Materials (NIOM), Norway.