Phthalocyanine aluminum chloride (Pc) is a clinically viable photosensitizer (PS) to treat skin lesions worsened by microbial infections. However, this molecule presents a high self-aggregation ...tendency in the biological fluid, which is an in vivo direct administration obstacle. This study proposed the use of bioadhesive and thermoresponsive hydrogels comprising triblock-type Pluronic F127 and Carbopol 934P (FCarb) as drug delivery platforms of Pc (FCarbPc)-targeting topical administration. Carbopol 934P was used to increase the F127 hydrogel adhesion on the skin. Rheological analyses showed that the Pc presented a low effect on the hydrogel matrix, changing the gelation temperature from 27.2 ± 0.1 to 28.5 ± 0.9 °C once the Pc concentration increases from zero to 1 mmol L–1. The dermatological platform showed matrix erosion effects with the release of loaded Pc micelles. The permeation studies showed the excellent potential of the FCarb platform, which allowed the partition of the PS into deeper layers of the skin. The applicability of this dermatological platform in photodynamic therapy was evaluated by the generation of reactive species which was demonstrated by chemical photodynamic efficiency assays. The low effect on cell viability and proliferation in the dark was demonstrated by in vitro assays using L929 fibroblasts. The FCarbPc fostered the inhibition of Staphylococcus aureus strain, therefore demonstrating the platform’s potential in the treatment of dermatological infections of microbial nature.
Display omitted
•S. aureus was killed by photodynamic inactivation using chlorophylls (Chls) as photosensitizer.•Photodynamic properties were dependent of the drug delivery system, micelles or ...liposome.•The photodynamic inactivation was related to Chls uptake to bacterial cells and Chls photophysical.•Phorbide derivatives in liposomes are indicated as promising photosensitizers for photodynamic therapy.
Chlorophyll derivatives (Chls), loaded in F-127 polymeric micelles and DPPC liposomes as drug delivery systems (DDS), have been shown to be remarkable photosensitizers for photodynamic inactivation (PDI). Assays of photoinactivation of Staphylococcus aureus bacteria (as biological models) showed that the effectiveness of Chls in these nanocarriers is dependent on photobleaching processes, photosensitizer locations in DDS, singlet oxygen quantum yields, and Chl uptake to bacteria. These are factors related to changes in Chl structure, such as the presence of metals, charge, and the phytyl chain. The photodynamic activity was significantly greater for Chls without the phytyl chain, i.e., phorbides derivatives. Furthermore, the inactivation of S. aureus was increased by the use of liposomes compared to micelles. Therefore, this research details and shows the high significance of the Chl structure and delivery system to enhance the photodynamic activity. It also highlights the chlorophylls (particularly phorbides) in liposomes as promising photosensitizers for PDI.
Hypericin (Hyp) is a potential photosensitizer drug for Photodynamic Therapy (PDT). However, the high lipophilicity of Hyp prevents its preparation in water. To overcome the Hyp solubility problem, ...this study uses the liposomal vesicle of DPPC. Otherwise liposome is also one of the most employed artificial systems that mimetizes cell membranes. Our present focus is the interaction of Hyp into DPPC liposome as biomimetic system. We studied the loading, interaction, and localization of Hyp (2.8 μmol L−1) in DPPC (5.4 mmol L−1) liposomes, as well as the thermodynamic aspects of Hyp-liposomes. The Hyp addition to the DPPC liposome dispersion showed a Encapsulation Efficiency for Hyp = 2.8 μmol L−1 in DPPC = 5.3 mmol L−1 of 74.3% and 89.3% at 30.0 and 50.0 °C, respectively. The encapsulation profile obeys a pseudo first-order kinetic law, with a rate constant of 1.26 × 10−3 s−1 at 30.0 °C. Also the data suggests this reaction is preceded by an extremely rapid step. A study on the binding of Hyp/DPPC liposomes (Kb), performed at several temperatures, showed results of 4.8 and 18.5 × 103 L mol−1 at 293 and 323 K, respectively. Additionally, a decrease was observed in the ΔG of the Hyp/DPPC interaction (−20.6 and − 26.4 kL mol−1 at 293 and 323 K, respectively). The resulting ΔH > 0 with ΔS < 0 shows that the entropy is driven the process. Studies of Hyp location in the liposome at 298 K revealed the existence of two different Hyp populations with a Stern-Volmer constant (Ksv) of 4.65 and 1.87 L mol−1 using iodide as an aquo-suppressor at concentration ranged from 0 to 0.025 mol L−1 and from 0.025 to 0.150 mol L−1, respectively. Furthermore, studies of Fluorescence Resonance Energy Transfer, using DPH as a donor and Hyp as an acceptor, revealed that Hyp is allocated in different binding sites of the liposome. This is dependent on temperature. Thermal studies revealed that the Hyp/DPPC formulation presented reasonable stability. Size and morphological investigations showed that Hyp incorporation increases the average size of DPPC liposomes from 116 to 154 nm. The study demonstrated the ability of the Hyp-DPPC liposome as an interesting system for drug delivery system that can be applied to PDT.
Display omitted
•Hyp/DPPC showed a pseudo first-order kinetic law.•Binding showed high Kb.•Location showed two Hyp populations.
Our study investigated the innate immune response to Toxoplasma gondii infection by assessing microglial phenotypic changes and sickness behavior as inflammatory response markers post-ocular ...tachyzoite instillation. Disease progression in Swiss albino mice was compared with the previously documented outcomes in BALB/c mice using an identical ocular route and parasite burden (2 × 105 tachyzoites), with saline as the control. Contrary to expectations, the Swiss albino mice displayed rapid, lethal disease progression, marked by pronounced sickness behaviors and mortality within 11–12 days post-infection, while the survivors exhibited no apparent signs of infection. Comparative analysis revealed the T. gondii-infected BALB/c mice exhibited reduced avoidance of feline odors, while the infected Swiss albino mice showed enhanced avoidance responses. There was an important increase in microglial cells in the dentate gyrus molecular layer of the infected Swiss albino mice compared to the BALB/c mice and their respective controls. Hierarchical cluster and discriminant analyses identified three microglial morphological clusters, differentially affected by T. gondii infection across strains. The BALB/c mice exhibited increased microglial branching and complexity, while the Swiss albino mice showed reduced shrunken microglial arbors, diminishing their morphological complexity. These findings highlight strain-specific differences in disease progression and inflammatory regulation, indicating lineage-specific mechanisms in inflammatory responses, tolerance, and resistance. Understanding these elements is critical in devising control measures for toxoplasmosis.
Safranine-O (Sf) is a photosensitizer (PS) displaying a remarkable potential for photodynamic therapy (PDT). In this work, we have used the combination of Sf with F127 Pluronic and Carbopol (C934P) ...to obtain a stimuli-responsive hydrogel (SR-Sf). This thermoresponsive-photoactive nanostructured system was prepared by two different methods: direct addition (DA) and solid dispersion (SD). Both SR-Sf have had their physical and chemical properties evaluated for veterinary applications, especially considering their ability to be used as a commercial product, aiming at the prophylactic or therapeutic treatment of breast gland infections. In general, the rheological and mechanical properties, as well as the sol–gel transition temperature, indicated suitable properties for using them as a topical system in veterinary (and human) applications. The ex vivo release studies showed a satisfactory permeation profile of the SR-Sf hydrogel, reaching the full length of the overall skin toward the dermis within 30 min of application (989 μm). The in vitro studies showed photodynamic inactivation using Sf-F127 with a significant reduction in isolated colonies. The in vivo case report with dairy goat demonstrated that the SR-Sf hydrogel veterinary use platform emerged as an innovative approach for the treatment of local infections without generating antibiotic residues in the milk produced.
The traditional use of essential oils in aromatherapy has offered numerous health benefits. However, few scientific studies have been conducted with these oils to confirm their therapeutic efficacy. ...(+)-Limonene is a chemical constituent of various bioactive essential oils. The present study reports on the anxiolytic-like effects of (+)-limonene in an elevated maze model of anxiety in mice. At concentrations of 0.5% and 1.0%, (+)-limonene, administered to mice by inhalation, significantly modified all the parameters evaluated in the elevated plus maze test. The pharmacological effect of inhaled (+)-limonene (1%) was not blocked by flumazenil. Analysis of (+)-limonene using gas chromatography–mass spectrometry (GC–MS) showed its volatility to be high. These data suggest possible connections between the volatility of (+)-limonene and its anxiolytic-like effect on the parameters evaluated in the elevated plus maze test. The data indicate that (+)-limonene could be used in aromatherapy as an antianxiety agent.
Display omitted
► Inhaled limonene ► Increases open entries and open duration in elevated plus-maze. ► Anxiolytic properties in mice
Therapy efficiency is ruled by a single agent, which can be enhanced using an adjuvant, increasing cell inhibition in a synergetic aspect. Taking this into account, the photosensitizers Pheophorbide ...and Zinc-Pheophorbide, and their physical chemical and photodynamic properties, were evaluated with Lapachol and β-lapachone drugs. They were incorporated into triblock copolymers P123 and F127 as biocompatible nanocarriers. Spectrophotometric studies showed photosensitizer monomerization in the combined formulation, a fundamental aspect for optimal photodynamic results. The apparent pKa studies of Lapachol incorporated in copolymeric micelles indicated small variations when compared to the data in a homogeneous medium (water/ethanol). This demonstrated the composition of 76% and 56% for deprotonated forms of Lapachol at the physiological pH, after administration of the formulated systems in F127 and P123, respectively. This preferential location is in the poly (ethylene oxide) interfacial bulk of the Pluronic®. The characterization of the photophysical properties of the combined systems showed an expressed decrease of fluorescence quantum yield of the PS in the β-lapachone based systems. This was attributed to greater suppression by collisions with water molecules due to variations in the accommodation region of the photosensitizer after simultaneous encapsulation. The combined system showed a decrease of singlet oxygen quantum yield due to high local micellar microviscosity and low molecular oxygen concentration. However, a five-fold increase in singlet oxygen lifetime was noted in systems within the nanostructured microenvironment, which enhances the range of photosensitizer action. The combined system showed marked thermal stability when subjected to refrigeration, which was below the critical micellar temperature for nanocarriers. This was true after subsequent reheating as well. In addition, the formulations were stored for prolonged periods in the lyophilized state that demonstrated the maintenance of the monomeric state of the photosensitizers. This is a desirable effect for photodynamic applications. The majority of the combined systems incorporated into the nanostructured microenvironment showed temporal stability for more than 96 h in an aqueous solution.
Photosensitizers (PS) and Naphthoquinones (Napht) are incorporated into nanocarriers. The mechanism of the PS action associated with Naphthoquinones, responsible for the formation of singlet oxygen and reactive oxygen species, will allow for treatment optimization and an increase in the rate of cell death. Display omitted
•The studies showed the monomerization of Pheophorbide and Zinc-Pheophorbide photosensitizers, even after the simultaneous incorporation of Lapachol and β-lapachone naphthoquinones in micellar nanostructured carrier systems.•Studies of apparent pKa of lapachol and self aggregation effects allowed for significant spectral variations after incorporation into the micellar nanostructured system, either single or in combination with photosensitizers.•Changes in the microenvironment of the photosensitizer after simultaneous incorporation led to a reduction in the fluorescence quantum yield of the photosensitizers combined with β-lapachone.•The combined system showed a five-fold increase in the lifetime of the singlet oxygen produced by Pheophorbide and Zinc-Pheophorbide, which increases the radius of action due to diffusion of singlet oxygen.
In line with environmental concerns, in this study we propose a new protocol to perform the photosynthesis of Hypericin (Hyp) from protohypericin (Protohyp) in aqueous medium. The kinetic parameters ...of the Protohyp-to-Hyp photoconversion were investigated in aqueous nanostructured systems formed by the non-polymeric surfactants SDS, CTAB and TX-100 as well as the P-123, F-127 and P-84 copolymers. In all surfactant systems evaluated it was possible to obtain Hyp from the Protohyp irradiation using a low power light source. The kinetic model of pseudo-first order was used for the theoretical fits of kinetic experimental data. Values of kinetic constants (k) in acetone (6.6 ms−1) and ethanol (7.8 ms−1) were used as references. Highest rate of Protohyp-to-Hyp photoconversion in non-polymeric systems were verified in SDS (k = 21.9 ms−1). As for copolymeric systems, the photoreaction happened more quickly in F-127 (k = 6.7 ms−1). Concomitantly with kinetic studies, investigations were conducted to evaluate the potential of Protohyp in a prodrug strategy aiming for Hyp. The photoconversion process was investigated in situ in a biological environment composed by Caco-2 intestinal colon carcinoma cells incubated with Protohyp (0.5 μmol L−1) formulated in P-123, F-127 and P-84 aqueous copolymeric system. The in vitro assays showed photodynamic activity in all systems evaluated, indicating that Hyp has been formed under suitable conditions to trigger the photosensitization process that results in cell death, without requiring the use of organic solvents.
Display omitted
•The photosynthetic step of the Hypericin preparation was successfully performed in microheterogeneous aqueous systems.•Kinetic rates of Protohyp-to-Hyp photoreaction were evaluated in non-polymeric and copolymeric surfactants.•Charge effects and polymeric structure modulate photoreaction rates in ionic and polymeric surfactant systems, respectively.•Protohyp-to-Hyp photoreaction presented potential to base a prodrug strategy in photodynamic therapy.
To determine the effect of rivers, environmental conditions, and isolation by distance on the distribution of species in Amazonia. Location: Brazilian Amazonia. Time period: Current. Major taxa ...studied: Birds, fishes, bats, ants, termites, butterflies, ferns + lycophytes, gingers and palms. We compiled a unique dataset of biotic and abiotic information from 822 plots spread over the Brazilian Amazon. We evaluated the effects of environment, geographic distance and dispersal barriers (rivers) on assemblage composition of animal and plant taxa using multivariate techniques and distance- and raw-data-based regression approaches. Environmental variables (soil/water), geographic distance, and rivers were associated with the distribution of most taxa. The wide and relatively old Amazon River tended to determine differences in community composition for most biological groups. Despite this association, environment and geographic distance were generally more important than rivers in explaining the changes in species composition. The results from multi-taxa comparisons suggest that variation in community composition in Amazonia reflects both dispersal limitation (isolation by distance or by large rivers) and the adaptation of species to local environmental conditions. Larger and older river barriers influenced the distribution of species. However, in general this effect is weaker than the effects of environmental gradients or geographical distance at broad scales in Amazonia, but the relative importance of each of these processes varies among biological groups.
Abstract Pediculosis mainly affects school-age children worldwide. The aim of this study was to identify and analyze the knowledge of the parents and guardians of children in elementary schools in ...Niterói, Brazil, regarding pediculosis. Questionnaires were applied to 237 guardians of children at five 1-5 grade municipal schools. The responses were analyzed and correlated with positivity to louse infestation, detected by scalp aspiration. 73.8% of the respondents reported that their child had already been infested with lice. 32.9% presented correct responses about transmission. Incorrect responses were attributed to the air/wind, blood type and the fact that lice jump and fly. 40.1% of the respondents erroneously correlated control over the parasitosis with hygiene. A majority of the participants (58.6%) responded that pediculosis is harmful to health, while a small proportion (20.7%) considered it to be a disease. The prevalence of pediculosis was 19.8% among schoolchildren. Female sex, pruritus on the head and indifference regarding infestation were shown to be risk factors for pediculosis. The lack of perception of pediculosis as a disease may lead to naturalization of this parasitosis. Incorrect responses may add difficulty to implementation of preventive and curative approaches, which highlights the importance of dissemination of correct information about pediculosis.
PDF
