1. Sulfobutylether-β-cyclodextrin/5,10,15,20-tetrakis(1-methylpyridinium-4-yl)porphine nanoassemblies with sustained antimicrobial phototherapeutic action.
- Author
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Zagami R, Franco D, Pipkin JD, Antle V, De Plano L, Patanè S, Guglielmino S, Monsù Scolaro L, and Mazzaglia A
- Subjects
- Anti-Infective Agents administration & dosage, Escherichia coli drug effects, Escherichia coli physiology, Excipients administration & dosage, Excipients chemical synthesis, Light adverse effects, Nanoparticles administration & dosage, Photosensitizing Agents administration & dosage, Porphyrins administration & dosage, Pseudomonas aeruginosa drug effects, Pseudomonas aeruginosa physiology, Staphylococcus aureus drug effects, Staphylococcus aureus physiology, beta-Cyclodextrins administration & dosage, Anti-Infective Agents chemical synthesis, Nanoparticles chemistry, Photochemotherapy methods, Photosensitizing Agents chemical synthesis, Porphyrins chemical synthesis, beta-Cyclodextrins chemical synthesis
- Abstract
Nowadays, novel less-expensive nanoformulations for in situ-controlled and safe delivery of photosensitisers (PSs) against opportunistic pathogens in body-infections areas need to be developed. Antimicrobial photodynamic therapy (aPDT) is a promising approach to treat bacterial infections that are recalcitrant to antibiotics. In this paper, we propose the design and characterization of a novel nanophototherapeutic based on the trade cyclodextrin CAPTISOL® (sulfobutylether-beta-cyclodextrin, SBE-βCD) and 5,10,15,20-tetrakis(1-methylpyridinium-4-yl)porphine tetrakis(p-toluenesulfonate) (TMPyP) to fabricate efficient biocompatible systems for aPDT. Spherical nanoassemblies of about 360 nm based on CAPTISOL®/TMPyP supramolecular complexes with 1:1 stoichiometry and apparent equilibrium binding constant (K
b ≅ 1.32 × 105 M-1 ) were prepared with entrapment efficiency of ≅ 100% by simple mixing in aqueous media and freeze-drying. These systems have been characterized by complementary spectroscopy and microscopy techniques. Time resolved fluorescence pointed out the strong interaction of porphyrin monomer within nanoassemblies (τ2 ≅ 11 ns with an amount of ca 90%) and scarce self-aggregation of porphyrins have been observed. Singlet oxygen comparative determination (ϕΔ CAPTISOL ®/TMPyP = 0.58) assessed their photodynamic potential. Release and photostability studies have been carried out under physiological conditions pointing out the role of CAPTISOL® to sustain porphyrin release for more than 2 weeks and to protect PS from photodegradation. Finally, photoantimicrobial activity of nanoassemblies vs free porphyrin have been investigated against Gram-negative P. aeruginosa, E. coli and Gram-positive S. aureus. The proposed nanosystems were able to photokill both Gram-positive and -negative bacterial cells similarly to TMPyP at MBC90 = 6 µM of TMPyP and at 42 J/cm2 light dose. However, with respect to the less selective free TMPyP in biological sites, nanoassemblies exhibit sustained release properties and a higher photostability thus optimizing the PDT effect at the site of action. These results can open routes for in vivo translational studies on nano(photo)drugs and nanotheranostics based on less expensive formulations of CD and PS., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)- Published
- 2020
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