Nowadays multi-drug resistant microorganisms is a serious public health problem worldwide. To overcome it, new antimicrobial strategies have been developed. Among them, antimicrobial photodynamic therapy is an efficient tool against various micro-organisms in different medical and healthcare fields. The antimicrobial photodynamic protocol is based on the interaction of a photosensitizer, molecular oxygen, and an appropriate light source. Herein, we described the main physical and chemical proprieties of curcumin, an useful natural photosensitizer, including its degradation pathways, analytical methods for quantification, extraction method, synthetic methodologies, and pharmaceutical formulations used. Moreover, a comprehensive review of the past 10 years (2010−2019) concerning the application of curcumin as photosensitizer against microorganisms is described and discussed.

Curcumin as a photosensitizer: From molecular structure to recent advances in antimicrobial photodynamic therapy

Curcumin (CUR) is a natural substance extracted from turmeric that has antimicrobial properties. Due to its ability to absorb light in the blue spectrum, CUR is also used as a photosensitizer (PS) in antimicrobial Photodynamic Therapy (aPDT). However, CUR is hydrophobic, unstable in solutions, and has low bioavailability, which hinders its clinical use. To circumvent these drawbacks, drug delivery systems (DDSs) have been used. In this review, we summarize the DDSs used to carry CUR and their antimicrobial effect against viruses, bacteria, and fungi, including drug-resistant strains and emergent pathogens such as SARS-CoV-2. The reviewed DDSs include colloidal (micelles, liposomes, nanoemulsions, cyclodextrins, chitosan, and other polymeric nanoparticles), metallic, and mesoporous particles, as well as graphene, quantum dots, and hybrid nanosystems such as films and hydrogels. Free (non-encapsulated) CUR and CUR loaded in DDSs have a broad-spectrum antimicrobial action when used alone or as a PS in aPDT. They also show low cytotoxicity, in vivo biocompatibility, and improved wound healing. Although there are several in vitro and some in vivo investigations describing the nanotechnological aspects and the potential antimicrobial application of CUR-loaded DDSs, clinical trials are not reported and further studies should translate this evidence to the clinical scenarios of infections.

Antimicrobial Activity of Curcumin in Nanoformulations: A Comprehensive Review.

Photodynamic therapy is witnessing a revival of its origins as a response to the rise of multi-drug resistant infections and the shortage of new classes of antibiotics. Photodynamic disinfection (PDDI) of microorganisms is making progresses in preclinical models and in clinical cases, and the perception of its role in the clinical armamentarium for the management of infectious diseases is changing. We review the positioning of PDDI from the perspective of its ability to respond to clinical needs. Emphasis is placed on the pipeline of photosensitizers that proved effective to inactivate biofilms, showed efficacy in animal models of infectious diseases or reached clinical trials. Novel opportunities resulting from the COVID-19 pandemic are briefly discussed. The molecular features of promising photosensitizers are emphasized and contrasted with those of photosensitizers used in the treatment of solid tumors. The development of photosensitizers has been accompanied by the fabrication of a variety of affordable and customizable light sources. We critically discuss the combination between photosensitizer and light source properties that may leverage PDDI and expand its applications to wider markets. The success of PDDI in the management of infectious diseases will ultimately depend on the efficacy of photosensitizers, affordability of the light sources, simplicity of the procedures, and availability of fast and efficient treatments.

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Photodynamic disinfection and its role in controlling infectious diseases.

Antimicrobial photodynamic therapy (aPDT) is promising for oral decontamination. Curcumin has been used as photosensitizer; however, the hydrophobic properties can negatively affect aPDT. This study evaluated the aPDT efficacy using Cur-loaded Pluronic® F-127 micelles against Streptococcus mutans and Candida albicans biofilms. Micelles characterization was performed by zeta potential, dynamic light scattering, transmission electron microscopy, absorption and fluorescence spectroscopy. Cur concentrations, cell viability by CFU mL-1 and confocal microscopy were determined. Data were analyzed by parametric and nonparametric tests under 5%. Cur-loaded Pluronic® F-127 exhibited spherical shape, suitable particle size (≤100 nm), adequate polydispersity index, best stability, lower photodegradation and autoaggregation compared to unloaded-Cur. Both microorganisms were sensitive to Cur-loaded Pluronic® F-127 micelles aPDT, with minimum inhibitory concentration (MIC) of 270 μm and 2.1093 μm for S. mutans and C. albicans suspended culture, respectively. Cur-loaded Pluronic® F-127 aPDT exhibited antibacterial/antifungal effect against the biofilms (~3 log10 reduction; P ≤ 0.05); however, similar to unloaded (P ≥ 0.05). Confocal images confirmed these results. Cur-loaded Pluronic® F-127 micelles exhibited good photo-chemical properties and may be a viable alternative to deliver Cur and to improve aPDT effect during the treatment of dental caries. Moreover, Pluronic® micelles can enhance the solubility, stability, permeability and control the release of Cur.

Curcumin-loaded Pluronic® F-127 Micelles as a Drug Delivery System for Curcumin-mediated Photodynamic Therapy for Oral Application.

Superficial and systemic fungal infections are essential problems for the modern health care system. One of the challenges is the growing resistance of fungi to classic antifungals and the constantly increasing cost of therapy. These factors force the scientific world to intensify the search for alternative and more effective methods of treatment. This paper presents an overview of new fungal inactivation methods using Photodynamic Antimicrobial Chemotherapy (PACT). The results of research on compounds from the groups of phenothiazines, xanthanes, porphyrins, chlorins, porphyrazines, and phthalocyanines are presented. An intensive search for a photosensitizer with excellent properties is currently underway. The formulation based on the existing ones is also developed by combining them with nanoparticles and common antifungal therapy. Numerous studies indicate that fungi do not form any specific defense mechanism against PACT, which deems it a promising therapeutic alternative.

Photosensitizers Mediated Photodynamic Inactivation against Fungi.

Antifungal effect of photodynamic therapy mediated by curcumin on Candida albicans biofilms in vitro

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Antifungal effect of photodynamic therapy mediated by curcumin on Candida albicans biofilms in vitro