Photo-responsive polymeric micelles for the light-triggered release of curcumin targeting antimicrobial activity

Nanocarriers have been successfully used to solubilize, deliver, and increase the bioavailability of curcumin (CUR), but slow CUR release rates hinder its use as a topical photosensitizer in antimicrobial photodynamic therapy. A photo-responsive polymer (PRP) was designed for the light-triggered release of CUR with an effective light activation-dependent antimicrobial response. The characterization of the PRP was compared with non-responsive micelles comprising Pluronics™ P123 and F127. According to the findings, the PRP formed photo-responsive micelles in the nanometric scale (< 100 nm) with a lower critical micelle concentration (3.74 × 10−4 M−1, 5.8 × 10−4 M−1, and 7.2 × 10−6 M−1 for PRP, F127, P123, respectively, at 25°C) and higher entrapment efficiency of CUR (88.7, 77.2, and 72.3% for PRP, F127, and P123 micelles, respectively) than the pluronics evaluated. The PRP provided enhanced protection of CUR compared to P123 micelles, as demonstrated in fluorescence quenching studies. The light-triggered release of CUR from PRP occurred with UV light irradiation (at 355 nm and 25 mW cm−2) and a cumulative release of 88.34% of CUR within 1 h compared to 80% from pluronics after 36 h. In vitro studies showed that CUR-loaded PRP was non-toxic to mammal cell, showed inactivation of the pathogenic microorganisms Candida albicans, Pseudomonas aeruginosa, and methicillin-resistant Staphylococcus aureus, and decreased biofilm biomass when associated with blue light (455  nm, 33.84 J/cm2). The findings show that the CUR-loaded PRP micelle is a viable option for antimicrobial activity

Antimicrobial Activity of Curcumin in Nanoformulations: A Comprehensive Review

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

Encapsulation of curcumin in polymeric nanoparticles for antimicrobial Photodynamic Therapy.

Curcumin (CUR) has been used as photosensitizer in antimicrobial Photodynamic Therapy (aPDT). However its poor water solubility, instability, and scarce bioavalibility hinder its in vivo application. The aim of this study was to synthesize curcumin in polymeric nanoparticles (NP) and to evaluate their antimicrobial photodynamic effect and cytoxicity. CUR in anionic and cationic NP was synthesized using polylactic acid and dextran sulfate by the nanoprecipitation method. For cationic NP, cetyltrimethylammonium bromide was added. CUR-NP were characterized by physicochemical properties, photodegradation, encapsulation efficiency and release of curcumin from nanoparticles. CUR-NP was compared with free CUR in 10% dimethyl sulfoxide (DMSO) as a photosensitizer for aPDT against planktonic and biofilms (mono-, dual- and triple-species) cultures of Streptococcus mutans, Candida albicans and Methicillin-Resistant Staphylococcus aureus. The cytotoxicity effect of formulations was evaluated on keratinocytes. Data were analysed by parametric (ANOVA) and non-parametric (Kruskal-Wallis) tests (α = 0.05). CUR-NP showed alteration in the physicochemical properties along time, photodegradation similar to free curcumin, encapsulation efficiency up to 67%, and 96% of release after 48h. After aPDT planktonic cultures showed reductions from 0.78 log10 to complete eradication, while biofilms showed no antimicrobial effect or reductions up to 4.44 log10. Anionic CUR-NP showed reduced photoinactivation of biofilms. Cationic CUR-NP showed microbicidal effect even in absence of light. Anionic formulations showed no cytotoxic effect compared with free CUR and cationic CUR-NP and NP. The synthesized formulations improved the water solubility of CUR, showed higher antimicrobial photodynamic effect for planktonic cultures than for biofilms, and the encapsulation of CUR in anionic NP reduced the cytotoxicity of 10% DMSO used for free CUR

Data_Sheet_1_Photo-responsive polymeric micelles for the light-triggered release of curcumin targeting antimicrobial activity.docx

Nanocarriers have been successfully used to solubilize, deliver, and increase the bioavailability of curcumin (CUR), but slow CUR release rates hinder its use as a topical photosensitizer in antimicrobial photodynamic therapy. A photo-responsive polymer (PRP) was designed for the light-triggered release of CUR with an effective light activation-dependent antimicrobial response. The characterization of the PRP was compared with non-responsive micelles comprising Pluronics™ P123 and F127. According to the findings, the PRP formed photo-responsive micelles in the nanometric scale (−4 M−1, 5.8 × 10−4 M−1, and 7.2 × 10−6 M−1 for PRP, F127, P123, respectively, at 25°C) and higher entrapment efficiency of CUR (88.7, 77.2, and 72.3% for PRP, F127, and P123 micelles, respectively) than the pluronics evaluated. The PRP provided enhanced protection of CUR compared to P123 micelles, as demonstrated in fluorescence quenching studies. The light-triggered release of CUR from PRP occurred with UV light irradiation (at 355 nm and 25 mW cm−2) and a cumulative release of 88.34% of CUR within 1 h compared to 80% from pluronics after 36 h. In vitro studies showed that CUR-loaded PRP was non-toxic to mammal cell, showed inactivation of the pathogenic microorganisms Candida albicans, Pseudomonas aeruginosa, and methicillin-resistant Staphylococcus aureus, and decreased biofilm biomass when associated with blue light (455  nm, 33.84 J/cm2). The findings show that the CUR-loaded PRP micelle is a viable option for antimicrobial activity.</p

Values of log₁₀(CFU/mL) of mono-species biofilm treated with free CUR.

<p>(A) <i>C</i>. <i>albicans</i>, (B) <i>S</i>. <i>mutans</i> and (C) MRSA. Bars charts show mean and standard deviation (error bars). The same letters show no statistical difference. C-L-: Control group without PS nor light. C-L+: Biofilm treated only with light (43.2 J/cm²). C+L-: Biofilm treated only with Cur at 1200 μM. C+L+: Biofilm submitted to aPDT with Cur at 1200 μM and 43.2 J/cm².</p

Photostability (values of absorbance) after different irradiation times observed for free CUR, anionic and cationic CUR-NP.

<p>Photostability (values of absorbance) after different irradiation times observed for free CUR, anionic and cationic CUR-NP.</p

CLSM images showing uptake of free CUR (C and D), anionic CUR-NP (E and F), and cationic CUR-NP (G and H) by the triple-species biofilm.

<p><b>Controls (A and B) were stained with SYTO-9</b>. <b>Samples were washed thrice with PBS (B, D, F, and H) or not washed at all (A, C, E, and G)</b>. Magnification: 20 μm. Blue arrows: coccus; red arrows: yeasts; white arrows: hyphaes.</p

Mean values of log₁₀(CFU/mL) of planktonic cultures.

<p>(A) <i>S</i>. <i>mutans</i>, (B) <i>C</i>. <i>albicans</i> and (C) MRSA. Error bars: standard deviation. The same letters show no statistical difference. C-L-: control group without PS nor light. C-L+: Planktonic culture treated with light only (43.2 J/cm²). C+L- free: Planktonic culture treated with free Cur only at 130 μM. C+L+ free: Planktonic culture submitted to aPDT with free Cur at 130 μM and 43.2 J/cm². N Anionic: Planktonic culture treated with anionic NP without CUR. C+L- Anionic: Planktonic cultures treated only with anionic CUR-NP at 130 μM. C+L+ Anionic: Planktonic culture submitted to aPDT with anionic CUR-NP at 130 μM and 43.2 J/cm². N Cationic: Planktonic culture treated with cationic NP without CUR. C+L- Cationic: Planktonic culture treated only with cationic CUR-NP at 130 μM. C+L+ Cationic: Planktonic culture submitted to aPDT with cationic CUR-NP at 130 μM and 43.2 J/cm².</p

Absorption spectrum of free CUR, anionic CUR-NP, and cationic CUR-NP.

<p>Absorption spectrum of free CUR, anionic CUR-NP, and cationic CUR-NP.</p