Local administration of curcumin-loaded nanoparticles enhances periodontal repair in vivo.

The aim was to assess the influence of local application of curcumin-loaded nanoparticles on an experimental model of periodontal repair. Periodontitis was induced by ligatures on both lower first molars of rats. After 15 days, ligatures were removed ("treatment") and animals were randomly allocated to three experimental groups (n = 8/group): (i) 0.05 mg/ml curcumin-loaded nanoparticles, (ii) empty nanoparticles (vehicle control), and (iii) sterile saline (negative control). Experimental treatments were administered locally on days 0, 3, 5, 7, 9, and 11 after ligature removal. Animals were euthanized at 7 and 14 days. Bone repair was assessed by microcomputer tomography (µCT). Histological sections were stained with hematoxylin/eosin (H/E), Picrosirius Red, and Masson's trichrome. Expression of Runx-2 was studied by immunohistochemistry. Gene expression of Itgam, Arg1, and Inos was assessed by RT-qPCR. At 7 days, there was increased gene expression of Itgam and Arg1 and of the relative expression of Arg1/Inos in curcumin-treated animals, but no difference in any other outcomes. At 14 days, curcumin-loaded nanoparticles significantly increased bone repair and collagen content, as well as the number of osteocytes, percentage of extracellular matrix, and expression of Runx2. The results demonstrate that local administration of curcumin-loaded nanoparticles enhanced tissue repair in an experimental model of periodontal repair. Nanoparticle-encapsulated curcumin enhances early post-treatment repair of periodontal tissues.

Tissue Engineering and Photodynamic Therapy: A New Frontier of Science for Clinical Application -An Up-To-Date Review.

Tissue engineering (TE) connects principles of life sciences and engineering to develop biomaterials as alternatives to biological systems and substitutes that can improve and restore tissue function. The principle of TE is the incorporation of cells through a 3D matrix support (scaffold) or using scaffold-free organoid cultures to reproduce the 3D structure. In addition, 3D models developed can be used for different purposes, from studies mimicking healthy tissues and organs as well as to simulate and study different pathologies. Photodynamic therapy (PDT) is a non-invasive therapeutic modality when compared to conventional therapies. Therefore, PDT has great acceptance among patients and proves to be quite efficient due to its selectivity, versatility and therapeutic simplicity. The PDT mechanism consists of the use of three components: a molecule with higher molar extinction coefficient at UV-visible spectra denominated photosensitizer (PS), a monochromatic light source (LASER or LED) and molecular oxygen present in the microenvironment. The association of these components leads to a series of photoreactions and production of ultra-reactive singlet oxygen and reactive oxygen species (ROS). These species in contact with the pathogenic cell, leads to its target death based on necrotic and apoptosis ways. The initial objective of PDT is the production of high concentrations of ROS in order to provoke cellular damage by necrosis or apoptosis. However, recent studies have shown that by decreasing the energy density and consequently reducing the production of ROS, it enabled a specific cell response to photostimulation, tissues and/or organs. Thus, in the present review we highlight the main 3D models involved in TE and PS most used in PDT, as well as the applications, future perspectives and limitations that accompany the techniques aimed at clinical use.

Magnetic and Highly Luminescent Heterostructures of Gd3+/ZnO Conjugated to GCIS/ZnS Quantum Dots for Multimodal Imaging.

In recent years, the use of quantum dots (Qdots) to obtain biological images has attracted attention due to their excellent luminescent properties and the possibility of their association with contrast agents for magnetic resonance imaging (MRI). In this study, Gd3+/ZnO (ZnOGd) were conjugated with Qdots composed of a gadolinium-copper-indium-sulphur core covered with a ZnS shell (GCIS/ZnS Qdots). This conjugation is an innovation that has not yet been described in the literature, and which aims to improve Qdot photoluminescent properties. Structural and morphological Qdots features were obtained by transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) and thermogravimetric analyses (TGA). The photoluminescent properties were examined by emission (PL) and excitation (PLE) spectra. A new ZnOGd and GCIS/ZnS (ZnOGd-GCIS/ZnS) nanomaterial was synthesized with tunable optical properties depending on the ratio between the two native Qdots. A hydrophilic or lipophilic coating, using 3-glycidyloxypropyltrimethoxysilane (GPTMS) or hexadecyltrimethoxysilane (HTMS) on the surface of ZnOGd-GCIS/ZnS Qdots, was carried out before assessing their efficiency as magnetic resonance contrast agents. ZnOGd-GCIS/ZnS had excellent luminescence and MRI properties. The new Qdots developed ZnOGd-GCIS/ZnS, mostly constituted of ZnOGd (75%), which had less cytotoxicity when compared to ZnOGd, as well as greater cellular uptake.

Antiviral activity of curcumin-nanoemulsion associated with photodynamic therapy in vulvar cell lines transducing different variants of HPV-16.

Vulvar intraepithelial neoplasia (VIN) is associated with human papillomavirus (HPV) infection. Curcumin is a natural bioactive compound with antineoplastic properties. The use of nanoparticles containing curcumin could allow a better performance of this compound in therapies. So, VIN biopsies were collected and HPV DNA detection was performed by PCR, positive samples were genotyped by Restriction Fragment Length Polymorphism (RFLP) and HPV-16 variants were determined by sequencing. HPV-16 positive vulva carcinoma cells (A431) were transduced with E-P and E-350G HPV-16 E6 variants. The viability of the transduced cells treated with nanoemulsions was determined by MTT assay. Besides, apoptosis was evaluated by enzymatic activity of Caspase-3/7. The cell viability assay showed that both the empty nanoemulsion (NE-V) and the nanoemulsion of curcumin (NE-CUR) had little effect on cell viability as compared to control cells. Additionally, we observed that cells irradiated in the presence of NE-CUR presented 90% of cell death. The apoptosis assay further revealed a significant increase in the activity of caspases 3 and 7 in A431 cells expressing both HPV-16 E6 variants after treatment with NE-CUR. Finally, we submitted the HPV transduced A431 cells to organotypic cultures and observed that the combination of treatments affected tissue architecture with evident signals of tissue damage. We concluded that nanoemulsions attain good biocompatibility, since no cytotoxicity was observed and NE-CUR associated with photoactivation showed promising results, leading to death only in cells subjected to irradiation. This drug delivery system associated with photodynamic therapy may become promising in the treatment of vulva lesions.

Effect of Curcumin-Nanoemulsion Associated with Photodynamic Therapy in Cervical Carcinoma Cell Lines.

Cervical cancer is the fourth cause of cancer death in women. Curcumin has antineoplastic properties. Furthermore, curcumin may be used as a photosensitizing agent in Photodynamic Therapy. This study aimed to investigate the effects of Photodynamic Therapy in cellular viability using curcumin-nanoemulsion as a photosensitizing drug in cervical carcinoma cell lines. The empty nanoemulsion presented very low cytotoxicity in all cell lines analyzed. Additionally, the incubation with curcumin-nanoemulsion at 20 µM of curcumin showed more than 80% of cell viability for cell lines. Nanoemulsions were shown to be internalized inside cells by fluorescence microscopy and were observed in the intracellular environment for up to 36 hours after incubation with cell lines. In addition, after the Photodynamic Therapy we observed a high phototoxic effect of the curcumin-nanoemulsion with less than 5% of viable cells after irradiation. This was accompanied by an increase in caspase-3/caspase-7 activities after cell treatment with curcumin-nanoemulsion and Photodynamic Therapy, suggesting cell death by apoptosis. We conclude that the curcumin-nanoemulsion formulation behaves as a photosensitizing drug in Photodynamic Therapy and shows potential as an alternative treatment to cervical lesions using an endoscopic diode fiber laser setup for in situ activation or cavity activation using a diffuse fiber delivery system.