Formulation and characterization of lyophilized curcumin solid dispersions for antimicrobial photodynamic therapy (aPDT): studies on curcumin and curcuminoids LII.
BACKGROUND
Bacterial resistance to antibiotics is increasing and alternative antibacterial treatments like antimicrobial photodynamic therapy (aPDT) are needed. Curcumin is under investigation as a potential photosensitizer in aPDT.


OBJECTIVE
The purpose of this study was to develop rapidly dissolving formulations of curcumin that could photoinactivate both Gram-positive and Gram-negative bacteria.


METHODS
Curcumin solid dispersions with methyl-β-cyclodextrin and hyaluronic acid (HA), hydroxypropyl methylcellulose (HPMC) or both HA and HPMC were prepared through lyophilization. The lyophilizates were characterized by curcumin drug load [% (w/w)], differential scanning calorimetry, photostability, thermal stability, their ability to form supersaturated solutions and by in vitro photoinactivation of Enterococcus faecalis and Escherichia coli.


CONCLUSIONS
The lyophilizates were amorphous solid dispersions with a curcumin drug load in the range of 1.4-5.5% (w/w) depending on the included polymer and the ratio between curcumin and the cyclodextrin. The lyophilizates were photolabile, but thermally stable and dissolved rapidly in contact with water to form supersaturated solutions. Selected lyophilizates demonstrated >log 6 reduction of colony forming units/ml of both E. faecalis and E. coli after exposure to low curcumin concentrations (0.5-10 µM) and blue light dose (11-16 J/cm(2)). The high drug load of the lyophilizates, rapid dissolution, ability to form relatively stable supersaturated solutions and the very high phototoxicity towards both E. faecalis and E. coli make these lyophilizates suitable for in vivo aPDT.


CONCLUSIONS
This treatment with optimized curcumin formulations should be explored as an alternative to topical antibiotics in the treatment of wound infections.
Department of Pharmacy, School of Pharmacy, University of Oslo , Blindern, Oslo , Norway and.
Kristine Opsvik
KO
Wikene
Anne Bee
AB
Hegge
Ellen
E
Bruzell
Hanne Hjorth
HH
Tønnesen
D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D003474:Curcumin / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D004355:Drug Stability; D013293:Enterococcus faecalis / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects; D005079:Excipients / Q000737:chemistry; D005612:Freeze Drying; D006820:Hyaluronic Acid / Q000737:chemistry; D065347:Hypromellose Derivatives / Q000737:chemistry; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D012995:Solubility; D047392:beta-Cyclodextrins / Q000737:chemistry
D000900:Anti-Bacterial Agents; D005079:Excipients; D017319:Photosensitizing Agents; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin; D065347:Hypromellose Derivatives; D006820:Hyaluronic Acid; D003474:Curcumin
Enterococcus faecalis; Escherichia coli; PDT; photosensitizer; supersaturation