Natural rubber latex-based biomaterials for drug delivery and regenerative medicine: Trends and directions.

Natural Rubber Latex (NRL) has shown to be a promising biomaterial for use as a drug delivery system to release various bioactive compounds. It is cost-effective, easy to handle, biocompatible, and exhibits pro-angiogenic and pro-healing properties for both soft and hard tissues. NRL releases compounds following burst and sustained release kinetics, exhibiting first-order release kinetics. Moreover, its pore density can be adjusted for tailored kinetics profiles. In addition, biotechnological applications of NRL in amblyopia, smart mattresses, and neovaginoplasty have demonstrated success. This comprehensive review explores NRL's diverse applications in biotechnology and biomedicine, addressing challenges in translating research into clinical practice. Organized into eight sections, the review emphasizes NRL's potential in wound healing, drug delivery, and metallic nanoparticle synthesis. It also addresses the challenges in enhancing NRL's physical properties and discusses its interactions with the human immune system. Furthermore, examines NRL's potential in creating wearable medical devices and biosensors for neurological disorders. To fully explore NRL's potential in addressing important medical conditions, we emphasize throughout this review the importance of interdisciplinary research and collaboration. In conclusion, this review advances our understanding of NRL's role in biomedical and biotechnological applications, offering insights into its diverse applications and promising opportunities for future development.

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.

Development of Biotechnological Photosensitizers for Photodynamic Therapy: Cancer Research and Treatment-From Benchtop to Clinical Practice.

Photodynamic therapy (PDT) is a noninvasive therapeutic approach that has been applied in studies for the treatment of various diseases. In this context, PDT has been suggested as a new therapy or adjuvant therapy to traditional cancer therapy. The mode of action of PDT consists of the generation of singlet oxygen (¹O2) and reactive oxygen species (ROS) through the administration of a compound called photosensitizer (PS), a light source, and molecular oxygen (3O2). This combination generates controlled photochemical reactions (photodynamic mechanisms) that produce ROS, such as singlet oxygen (¹O2), which can induce apoptosis and/or cell death induced by necrosis, degeneration of the tumor vasculature, stimulation of the antitumor immune response, and induction of inflammatory reactions in the illuminated region. However, the traditional compounds used in PDT limit its application. In this context, compounds of biotechnological origin with photosensitizing activity in association with nanotechnology are being used in PDT, aiming at its application in several types of cancer but with less toxicity toward neighboring tissues and better absorption of light for more aggressive types of cancer. In this review, we present studies involving innovatively developed PS that aimed to improve the efficiency of PDT in cancer treatment. Specifically, we focused on the clinical translation and application of PS of natural origin on cancer.

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.

Local application of curcumin-loaded nanoparticles as an adjunct to scaling and root planing in periodontitis: Randomized, placebo-controlled, double-blind split-mouth clinical trial.

OBJECTIVE: Assess a single local application of curcumin-loaded nanoparticles as an adjunct to scaling and root planing (SRP) in nonsurgical periodontal treatment (NPT). MATERIALS AND METHODS: Twenty healthy subjects with periodontitis received SRP+PLGA/PLA nanoparticles loaded with 50 µg of curcumin (N-Curc) or SRP+empty nanoparticles. Probing pocket depth (PPD), clinical attachment level (CAL), and bleeding on probing (BOP) were monitored at baseline, 30, 90, and 180 days. IL-1α, IL-6, TNFα, and IL-10 in the gingival crevicular fluid (GCF) were assessed by ELISA, and counts of 40 bacterial species were determined by DNA hybridization at baseline, 3, 7, and 15 days post-therapy. RESULTS: PPD, CAL, and BOP were similarly and significantly improved in both experimental groups. There was no difference in GCF cytokine levels between experimental groups, although IL-6 was decreased at 3 days only in the N-Curc group. NPT reduced counts of red complex bacterial species in both groups. Veillonella Parvula counts increased significantly only in N-Curc group at 7 days, whereas Aggregatibacter actinomycetemcomitans counts increased significantly only in the control group from day 3 to day 15. CONCLUSION: We conclude that a single local administration of nanoencapsulated curcumin in periodontally diseased sites had no additive benefits to NPT. CLINICAL RELEVANCE: Our results showed that a single local application of curcumin-loaded nanoparticles associated with nonsurgical periodontal therapy did not improve clinical outcomes. Hence, our findings do not support the use of curcumin as an adjunct to nonsurgical periodontal therapy.

Photodynamic inactivation of Candida albicans and Candida tropicalis with aluminum phthalocyanine chloride nanoemulsion.

The in vitro susceptibilities of Candida albicans and Candida tropicalis to Antimicrobial Photodynamic Treatment with aluminum phthalocyanine chloride in nanoemulsion (ClAlPc/NE) were investigated. PS concentration- and fluence-dependent cell survival after APDT were compared before and after unbound extracellular PS had been washed out. The PS uptake and its subcellular localization were also determined. Exposure to light in the absence of the PS and treatment with the PS in the absence of light did not kill the fungi. APDT with ClAlPc/NE resulted in a reduction of five orders of magnitude in viability for C. albicans and between four and five orders of magnitude for C. tropicalis. Washing the cells to remove unbound PS before light exposure did not impair fungal inactivation, suggesting that cell photosensitization was mainly carried out by cell bound ClAlPc. The degree of ClAlPc uptake was dependent on its concentration. Internalization of ClAlPc by C. albicans and C. tropicalis was confirmed by confocal fluorescence microscopy that showed the PS does not penetrate the nucleus and instead accumulates in specific regions of the cytoplasm. Our results show that incorporating the water-insoluble ClAlPc into a nanoemulsion leads to an efficient formulation capable of photoinactivating both Candida species.

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.

Experimental study of the neurotoxic effects of photodynamic therapy on the spinal cord / Estudo experimental dos efeitos neurotóxicos da terapia fotodinâmica na medula espinhal / Estudio experimental de los efectos neurotóxicos de la terapia fotodinámica en la médula espinal

ABSTRACT Objective To evaluate the effects of photodynamic therapy (PDT) on the dura mater using the photosensitizers aluminum chloride phthalocyanine and methylene blue in in vivo assays. Methods Fifty-six male Wistar rats were divided into two groups; one submitted to PDT and the other submitted to the photosensitizers without their photoactivation (control). The photosensitizers were applied to the dura mater after laminectomy at the T10 level. The methods used for assessment were the Basso, Beattie and Bresnahan (BBB) functional evaluation scale and study of the dura mater by light microscopy. Results No changes in motor activity were observed in the animals submitted to PDT compared to control. Histological and pathological evaluation did not show any differences between the group exposed to activated photosensitizers and the control group with regard to the inflammatory process and tissue necrosis. Conclusion The joint use of PDT with the photosensitizing pharmaceuticals aluminum chloride phthalocyanine and methylene blue did not induce any clinical neurotoxic effects or histological changes in the dura mater of the animals studied. Level de evidence V; Expert Opnion.

RESUMO Objetivo Avaliar os efeitos da terapia fotodinâmica (PDT) na dura-máter usando os fotossensibilizadores cloreto de alumínio ftalocianina e azul de metileno em ensaios in vivo. Métodos Cinquenta e seis ratos Wistar machos divididos em dois grupos; um submetido à PDT e o outro submetido aos fotossensibilizadores sem a fotoativação (controle). Os fotossensibilizadores foram aplicados sobre a dura-máter depois de laminectomia no nível T10. Os métodos de avaliação usados foram a escala de avaliação funcional de Basso, Beattie e Bresnahan (BBB) e o estudo da dura-máter por microscopia óptica. Resultados Não foram observadas alterações da atividade motora dos animais submetidos à PDT com relação ao grupo controle. A avaliação histológica e histopatológica não mostrou diferenças entre o grupo exposto aos fotossensibilizadores ativados e o grupo controle, com relação ao processo inflamatório e à necrose tecidual. Conclusões O uso conjunto de PDT e os fármacos fotossensibilizantes cloreto de alumínio ftalocianina e azul de metileno não induziu efeitos neurotóxicos clínicos e/ou alterações histológicas sobre a dura-máter dos animais estudados. Nível de evidência V; Opinião de Especialista.

RESUMEN Objetivo Evaluar los efectos de la terapia fotodinámica (PDT) en la duramadre utilizando los fotosensibilizadores de ftalocianina de aluminio clorada y azul de metileno en ensayos in vivo. Métodos Cincuenta y seis ratas Wistar machos se dividieron en 2 grupos; uno fue sometido a PDT y el otro sometido a fotosensibilizadores sin fotoactivación (control). Los fotosensibilizadores se aplicaron a la duramadre después de la laminectomía en el nivel T10. Los métodos de evaluación utilizados fueron la escala de evaluación funcional de Basso, Beattie y Bresnahan (BBB) y el estudio de la duramadre mediante microscopía óptica. Resultados No hubo cambios en la actividad motora de los animales sometidos a PDT en relación con el grupo de control. La evaluación histológica e histopatológica no mostró diferencias entre el grupo expuesto a fotosensibilizadores activados y el grupo de control con respecto al proceso inflamatorio y la necrosis tisular. Conclusiones El uso conjunto de PDT con las sustancias fotosensibilizadores ftalocianina de aluminio clorada y azul de metileno no indujo efectos neurotóxicos clínicos o cambios histológicos en la duramadre de los animales estudiados. Nivel de evidencia V; Opinión del Especialista.

Effect of curcumin-nanoemulsion associated with photodynamic therapy in breast adenocarcinoma cell line.

Curcumin, a natural compound has several antineoplastic activities and is a promising natural photosensitizer used in photodynamic therapy. However, its low solubility in physiological medium limit the clinical use of curcumin. This study aimed to analyze the action of curcumin-nanoemulsion, a new and well-designed Drug Delivery System (DDS+) molecule, used as a photosensitizing agent in photodynamic therapy in an in vitro breast cancer model, MCF-7 cells. The empty nanoemulsion fulfils all necessary requirements to be an excellent DDS. Furthermore, the use of curcumin-nanoemulsion in photodynamic therapy resulted in a high phototoxic effect after activation at 440 nm, decreasing to <10% viable tumor cells after two irradiations and increasing the reactive oxygen species (ROS) production. The use of curcumin-nanoemulsion associated with photodynamic therapy resulted in an increase in the levels of caspase 3/7 activity for the studied MCF-7 cell model, indicating that this therapy triggers a cascade of events that lead to cell death, such as cellular apoptosis. In conclusion, curcumin-nanoemulsion proved to be efficient as a photosensitizing agent, had phototoxic effects, significantly decreased the proliferation of MCF-7 cells and stimulating the ROS production in combination with photodynamic therapy, so, this formulation has a great potential for use in treatment of breast cancer.

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.

Acetylated cashew gum-based nanoparticles for transdermal delivery of diclofenac diethyl amine.

Nanoprecipitation and dialysis methods were employed to obtain nanoparticles (NPs) of acetylated cashew gum (ACG). NPs synthesized by dialysis showed greater average size compared to those synthesized by nanoprecipitation, but they presented improved stability and yield. NPs were loaded with diclofenac diethylamine and the efficiency of the drug incorporation was over 60% for both methods, for an ACG:NP a weight ratio of 10:1. The cytotoxicity assay demonstrated that the NPs had no significant effect on the cell viability, verifying their biocompatibility. The release profile for the diclofenac diethylamine associated with the ACG-NPs showed a more controlled release compared to the free drug and a Fickian diffusion mechanism was observed. Transdermal permeation reached 90% penetration of the drug.

Evaluation of the efficacy of systemic miltefosine associated with photodynamic therapy with liposomal chloroaluminium phthalocyanine in the treatment of cutaneous leishmaniasis caused by Leishmania (L.) amazonensis in C57BL/6 mice.

BACKGROUND: The shortage of drugs is a concern and has become the object of studies to discover effective alternatives for cutaneous leishmaniasis (CL) treatment. A topical formulation has been sought due to its low toxicity. Development of alternative therapies, such as multimodal ones, is important in confronting drug resistance. This study aims to compare the in vivo efficacy of topical photodynamic therapy (PDT) using liposomal chloroaluminium phthalocyanine (AlClPC) in the treatment of CL, isolated and associated with systemic therapy with miltefosine. METHODS: Five groups were adopted, each one with six isogenic adult female mice C57BL/6: (1) Negative Control-non-infected and non-treated; (2) Positive Control (PBS)-infected and non-treated; (3) Miltefosine-infected and treated with oral miltefosine 200 mg/kg/day; (4) Infected and treated with PDT with topical AlClPC (500 µL) on alternate days; (5) Oral Miltefosine 200 mg/kg/day and PDT with topical AlClPC (500 µL) on alternate days. Therapeutic schemes lasted 20 days. Infection was confirmed by culture in Nove-McNeal-Nicolle medium (NNN) of lymph collected from the animal paw, and animals were evaluated by paw measurement and parasitological criteria. RESULTS: Miltefosine associated with PDT with AlClPC promoted a significant reduction in parasite number and viability when compared to the other infected groups, also returning the paw diameter to a size similar to the negative control group after 20 days of treatment. CONCLUSIONS: Association of miltefosine with PDT mediated by topical AlClPC represents hopes for CL treatment, an increasing dermatological disease in some countries.

Genotoxicity assessment of reactive and disperse textile dyes using human dermal equivalent (3D cell culture system).

Thousands of dyes are marketed daily for different purposes, including textile dyeing. However, there are several studies reporting attributing to dyes deleterious human effects such as DNA damage. Humans may be exposed to toxic dyes through either ingestion of contaminated waters or dermal contact with colored garments. With respect to dermal exposure, human skin equivalents are promising tools to assess in vitro genotoxicity of dermally applied chemicals using a three-dimensional (3D) model to mimic tissue behavior. This study investigated the sensitivity of an in-house human dermal equivalent (DE) for detecting genotoxicity of textile dyes. Two azo (reactive green 19 [RG19] and disperse red 1[DR1]) dyes and one anthraquinone (reactive blue 2 [RB2]) dye were analyzed. RG19 was genotoxic for DE in a dose-responsive manner, whereas RB2 and DR1 were nongenotoxic under the conditions tested. These findings are not in agreement with previous genotoxicological assessment of these dyes carried out using two-dimensional (2D) cell cultures, which showed that DR1 was genotoxic in human hepatoma cells (HepG2) and RG19 was nongenotoxic for normal human dermal fibroblasts (NHDF). These discrepant results probably may be due to differences between metabolic activities of each cell type (organ-specific genotoxicity, HepG2 and fibroblasts) and the test setup systems used in each study (fibroblasts cultured at 2D and three-dimensional [3D] culture systems). Genotoxicological assessment of textile dyes in context of organ-specific genotoxicity and using in vitro models that more closely resemble in vivo tissue architecture and physiology may provide more reliable estimates of genotoxic potential of these chemicals.

Effects of Photodynamic Process (PDP) in Implant Osseointegration: A Histologic and Histometric Study in Dogs.

BACKGROUND: The combination between photosensitivity substances with laser or light-emitting diode (LED) form the photodynamic therapy basis that consists of photosensitivity drug activated by low-frequency light. This mechanism is used in soft tissue healing process to improve the oxygen tension leading to a fast revascularization. PURPOSE: The objective of this study was to evaluate the effects of photosensitivity drugs activated through LED on osseointegration process. MATERIALS AND METHODS: Eight mongrel dogs underwent implant therapy in four mandibular bone defects using 5.0 mm trephine drill on each side of the mandible. The defects were randomly filled up with (1) Nano emulsion, (2) liposome, (3) blood clot, and (4) autogenous bone. LED with visible and infrared light were applied after 48/72 postoperative hours on four dogs and after 96/120 postoperative hours in the other four dogs. All the animals were euthanized at 15 days after surgery. Ground sections slides were prepared from the experimental site for histomorphometry and histological analysis. RESULTS: No difference was detected in the following parameters: bone-implant contact, bone inside the defect and crest level on LED 48/72. Significant difference was detected inside the defect when filled with autogenous bone (p = .0238) on LED 96/120. When LED 48/72 and LED 96/120 were compared, significant higher bone formation was detected when autogenous bone on bone-implant contact (p = .0043) and bone inside the defect (p = .0008) was used. CONCLUSION: The use of photosensitivity drugs activated by LED demonstrated a tendency to stimulate bone formation, similar to autogenous bone graft on later time point.

Collagen-based silver nanoparticles for biological applications: synthesis and characterization.

BACKGROUND: Type I collagen is an abundant natural polymer with several applications in medicine as matrix to regenerate tissues. Silver nanoparticles is an important nanotechnology material with many utilities in some areas such as medicine, biology and chemistry. The present study focused on the synthesis of silver nanoparticles (AgNPs) stabilized with type I collagen (AgNPcol) to build a nanomaterial with biological utility. Three formulations of AgNPcol were physicochemical characterized, antibacterial activity in vitro and cell viability assays were analyzed. AgNPcol was characterized by means of the following: ultraviolet-visible spectroscopy, dynamic light scattering analysis, Fourier transform infrared spectroscopy, atomic absorption analysis, transmission electron microscopy and of X-ray diffraction analysis. RESULTS: All AgNPcol showed spherical and positive zeta potential. The AgNPcol at a molar ratio of 1:6 showed better characteristics, smaller hydrodynamic diameter (64.34 ± 16.05) and polydispersity index (0.40 ± 0.05), and higher absorbance and silver reduction efficiency (0.645 mM), when compared with the particles prepared in other mixing ratios. Furthermore, these particles showed antimicrobial activity against both Staphylococcus aureus and Escherichia coli and no toxicity to the cells at the examined concentrations. CONCLUSIONS: The resulted particles exhibited favorable characteristics, including the spherical shape, diameter between 64.34 nm and 81.76 nm, positive zeta potential, antibacterial activity, and non-toxicity to the tested cells (OSCC).

Chloroaluminium phthalocyanine polymeric nanoparticles as photosensitisers: photophysical and physicochemical characterisation, release and phototoxicity in vitro.

Nanoparticles of poly(d,l-lactide-co-glycolide), poly(d,l-lactide) and polyethylene glycol-block-poly(d,l-lactide) were developed to encapsulate chloroaluminium phthalocyanine (AlClPc), a new hydrophobic photosensitiser used in photodynamic therapy (PDT). The mean nanoparticle size varied from 115 to 274 nm, and the encapsulation efficiency ranged from 57% to 96% due to drug precipitation induced by different types of polymer. All nanoparticle formulations presented negative zeta potential values (-37 mV to -59 mV), explaining their colloidal stability. The characteristic photophysical parameters were analysed: the absorption spectrum profile, fluorescence quantum yield and transient absorbance decay, with similar values for free and nanoparticles of AlClPc. The time-resolved spectroscopy measurements for AlClPc triplet excited state lifetimes indicate that encapsulation in nanocapsules increases triplet lifetime, which is advantageous for PDT efficiency. A sustained release profile over 168 h was obtained using external sink method. An in vitro phototoxic effect higher than 80% was observed in human fibroblasts at low laser light doses (3 J/cm(2)) with 10 µM of AlClPc. The AlClPc loaded within polymeric nanocapsules presented suitable physical stability, improved photophysical properties, sustained released profile and suitable activity in vitro to be considered a promising formulation for PDT.

Photodynamic inactivation of planktonic cultures and biofilms of Candida albicans mediated by aluminum-chloride-phthalocyanine entrapped in nanoemulsions.

New drug delivery systems, such as nanoemulsions (NE), have been developed to allow the use of hydrophobic drugs on the antimicrobial photodynamic therapy. This study evaluated the photodynamic potential of aluminum-chloride-phthalocyanine (ClAlPc) entrapped in cationic and anionic NE to inactivate Candida albicans planktonic cultures and biofilm compared with free ClAlPc. Fungal suspensions were treated with different delivery systems containing ClAlPc and light emitting diode. For planktonic suspensions, colonies were counted and cell metabolism was evaluated by XTT assay. Flow cytometry evaluated cell membrane damage. For biofilms, the metabolic activity was evaluated by XTT and ClAlPc distribution through biofilms was analyzed by confocal laser scanning microscopy (CLSM). Fungal viability was dependent on the delivery system, superficial charge and light dose. Free ClAlPc caused photokilling of the yeast when combined with 100 J cm(-2). Cationic NE-ClAlPc reduced significantly both colony counts and cell metabolism (P < 0.05). In addition, cationic NE-ClAlPc and free ClAlPc caused significant damage to the cell membrane (P < 0.05). For the biofilms, cationic NE-ClAlPc reduced cell metabolism by 70%. Anionic NE-ClAlPc did not present antifungal activity. CLSM showed different accumulation on biofilms between the delivery systems. Although NE system showed a lower activity for planktonic culture, cationic NE-ClAlPc showed better results for Candida biofilms.

The effect of photosensitizer drugs and light stimulation on osteoblast growth.

OBJECTIVE: A promising new treatment in dentistry involves the photodynamic process, which utilizes a combination of two therapeutic agents, namely a photosensitizer drug and a low dose of visible light. We investigated the in vitro effect of low intensity laser irradiation (visible light irradiation at 670 nm) using doses ranging between 0.5 and 3 J/cm(2), combined with nanoemulsion (NE) of the photosensitizer drug aluminum phthalocyanine chloride (AlClPc), ranging from 0.5 to 5 µmol/L, on the growth and differentiation of osteoblastic cells isolated from rat bone marrow. BACKGROUND DATA: Treatments using laser radiation of low intensity in dentistry are of great interest, especially in bucco-maxillofacial surgery and dental implantology, where this approach is currently employed to stimulate osteogenesis. In the presence of oxygen, the combination of these agents could induce cellular biostimulation, via an efficient noninvasive method. METHODS: We have done the colorimetric MTT assay, collagen content, total protein content, ALP activity and bone-like nodule formation. RESULTS: We observed that an increased number of viable cells was evident upon application of a laser dosage equal to 0.5 J/cm(2) when combined with 0.5 µmol/L of AlClPc/NE, suggesting cellular biostimulation. CONCLUSIONS: It was possible to demonstrate that low intensity laser irradiation can play an important role in promoting biostimulation of osteoblast cell cultures. Therefore, whether biostimulation of osteoblastic cell cultures by photodynamic therapy or the cytotoxic effect of this therapy occurs only depends upon the light dose, and the results can be completely reversed.

Photoinduced nitric oxide and singlet oxygen release from ZnPC liposome vehicle associated with the nitrosyl ruthenium complex: synergistic effects in photodynamic therapy application.

Under continuous photolysis at 675 nm, liposomal zinc phthalocyanine associated with nitrosyl ruthenium complex [Ru(NH.NHq)(tpy)NO](3+) showed the detection and quantification of nitric oxide (NO) and singlet oxygen ((1)O(2)) release. Photophysical and photochemical results demonstrated that the interaction between the nitrosyl ruthenium complex and the photosensitizer can enable an electron transfer process from the photosensitizer to the nitrosyl ruthenium complex which leads to NO release. Synergistic action of both photosensitizers and the nitrosyl ruthenium complex results in the production of reactive oxygen species and reactive nitrogen species, which is a potent oxidizing agent to many biological tissues, in particular neoplastic cells.