RESUMO

Photodynamic therapy (PDT) using methylene blue (MB) as a photosensitizer has emerged as an alternative treatment for skin cancers, such as squamous cell carcinoma (SCC). To increase the cutaneous penetration of the drug, some strategies are used, such as the association of nanocarriers and physical methods. Thus, herein we address the development of nanoparticles based on poly-Ɛ-caprolactone (PCL), optimized with the Box-Behnken factorial design, for topical application of MB associated with sonophoresis. The MB-nanoparticles were developed using the double emulsification-solvent evaporation technique and the optimized formulation resulted in an average size of 156.93 ± 8.27 nm, a polydispersion index of 0.11 ± 0.05, encapsulation efficiency of 94.22 ± 2.19% and zeta potential of -10.08 ± 1.12 mV. Morphological evaluation by scanning electron microscopy showed spherical nanoparticles. In vitro release studies show an initial burst compatible with the first-order mathematical model. The nanoparticle showed satisfactory generation of reactive oxygen species. The MTT assay was used to assess cytotoxicity and IC50; values of 79.84; 40.46; 22.37; 9.90 µM were obtained, respectively, for the MB-solution and the MB-nanoparticle without and with light irradiation after 2 h of incubation. Analysis using confocal microscopy showed high cellular uptake for the MB-nanoparticle. With regard to skin penetration, a higher concentration of MB was observed in the epidermis + dermis, corresponding to 9.81, 5.27 µg/cm2 in passive penetration and 24.31 and 23.81 µg/cm2 after sonophoresis, for solution-MB and nanoparticle-MB, respectively. To the best of our knowledge, this is the first report of MB encapsulation in PCL nanoparticles for application in skin cancer using PDT.

RESUMO

The objective of this study was to analyze the effectiveness of phonophoresis with copaiba oil gel, in comparison to therapeutic pulsed ultrasound alone or topical application of copaiba oil gel, on oxidative stress after a traumatic muscle injury. Forty male Wistar rats were divided into five groups: control, muscle injury, therapeutic pulsed ultrasound (TPU), copaiba oil gel (CO) and TPU plus CO. TPU and CO application occurred at 2, 12, 24, 48, 72 and 96 h after injury. The gastrocnemius muscle was injured by mechanical trauma. Malondialdehyde (a lipoperoxidation marker) and superoxide dismutase and catalase (antioxidant enzymes) were assessed 98 h after muscle injury. All were elevated in the muscle injury group. There was a significant difference among treatment groups favoring TPU plus CO for reducing malondialdehyde levels, but all treatments reduced superoxide dismutase and catalase activity, with no between-groups difference. In conclusion, phonophoresis-the application of TPU plus CO-was superior to TPU or CO alone for reducing lipoperoxidation. Phonophoresis, TPU alone and CO were all effective in decreasing antioxidant enzyme activity after a traumatic skeletal muscle injury.

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Polymethylmethacrylate bone cement is a standard material used as antibiotic carrier in the orthopedic surgery. The ultrasonic energy method is capable of triggering biological effects based on both thermal and non-thermal mechanisms. The aim of the current study is to analyze methylene blue dispersion in polymethylmethacrylate beads, in association with the acoustic field generated by non-thermal ultrasound. Forty-nine specimens were used, and each specimen comprised one polymethylmethacrylate bead (0.6-mm diameter) doped with methylene blue and deposited in gelatin sample. Forty test specimens were divided into four groups comprising 10 samples, each, based on different ultrasound intensities (Group 1: 1.0 W/cm2; Group 2: 1.5 W/cm2) and polymethylmethacrylate bead depths (A - 2 cm; B - 3 cm) in gelatin sample. The control group comprised other nine specimens and statistically differed from the other groups. All groups irradiated with ultrasound have shown statistically significant differences in methylene blue dispersion, except for Groups 2A and 2B. Methylene blue dispersion in gelatin among groups was 1A> 1B; 2A> 1A; 2B> 1A; 2A> 1B; and 2B> 1B. Low-intensity ultrasound enabled the highest methylene blue dispersion when polymethylmethacrylate bead was positioned superficial; bead depth associated with high-intensity ultrasound did not influence methylene blue dispersion.

O cimento ósseo de polimetilmetacrilato é considerado um material padrão como carreador de antibiótico em cirurgias ortopédicas. A energia ultrassônica é um método capaz de gerar efeitos biológicos por mecanismos térmicos e não térmicos. Este estudo teve como objetivo analisar a dispersão de azul de metileno em pérolas de polimetilmetacrilato combinada com a exposição em campo acústico gerado por ultrassom não térmico. Foram utilizados 49 corpos-de-prova, cada um composto por uma pérola de polimetilmetacrilato (0,6 mm de diâmetro) dopada com azul de metileno e depositada em amostra de gelatina. Quarenta espécimes foram divididos em quatro grupos de 10 amostras com base nas intensidades de ultrassom (Grupo 1: 1,0 W/cm2; Grupo 2: 1,5 W/cm2) e profundidade (A - 2 cm; B - 3 cm) dos grânulos de polimetilmetacrilato na amostra de gelatina. Os outros nove espécimes constituíram o grupo controle. O grupo controle diferiu estatisticamente dos outros grupos. Todos os grupos irradiados com ultrassom apresentaram diferenças significativas, exceto os Grupos 2A e 2B. A dispersão de azul de metileno na gelatina entre os grupos foi: 1A> 1B; 2A> 1A; 2B> 1A; 2A> 1B; 2B> 1B. Ultrassom de baixa intensidade permitiu maior dispersão de azul de metileno com polimetilmetacrilato posicionado mais superficialmente, e não ocorreu influência da profundidade da pérola com ultrassom de alta intensidade.

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RESUMO

O cimento ósseo de polimetilmetacrilato é considerado um material padrão como carreador de antibiótico em cirurgias ortopédicas. A energia ultrassônica é um método capaz de gerar efeitos biológicos por mecanismos térmicos e não térmicos. Este estudo teve como objetivo analisar a dispersão de azul de metileno em pérolas de polimetilmetacrilato combinada com a exposição em campo acústico gerado por ultrassom não térmico. Foram utilizados 49 corpos-de-prova, cada um composto por uma pérola de polimetilmetacrilato (0,6 mm de diâmetro) dopada com azul de metileno e depositada em amostra de gelatina. Quarenta espécimes foram divididos em quatro grupos de 10 amostras com base nas intensidades de ultrassom (Grupo 1: 1,0 W/cm2; Grupo 2: 1,5 W/cm2) e profundidade (A - 2 cm; B - 3 cm) dos grânulos de polimetilmetacrilato na amostra de gelatina. Os outros nove espécimes constituíram o grupo controle. O grupo controle diferiu estatisticamente dos outros grupos. Todos os grupos irradiados com ultrassom apresentaram diferenças significativas, exceto os Grupos 2A e 2B. A dispersão de azul de metileno na gelatina entre os grupos foi: 1A> 1B; 2A> 1A; 2B> 1A; 2A> 1B; 2B> 1B. Ultrassom de baixa intensidade permitiu maior dispersão de azul de metileno com polimetilmetacrilato posicionado mais superficialmente, e não ocorreu influência da profundidade da pérola com ultrassom de alta intensidade.

Polymethylmethacrylate bone cement is a standard material used as antibiotic carrier in the orthopedic surgery. The ultrasonic energy method is capable of triggering biological effects based on both thermal and non-thermal mechanisms. The aim of the current study is to analyze methylene blue dispersion in polymethylmethacrylate beads, in association with the acoustic field generated by non-thermal ultrasound. Forty-nine specimens were used, and each specimen comprised one polymethylmethacrylate bead (0.6-mm diameter) doped with methylene blue and deposited in gelatin sample. Forty test specimens were divided into four groups comprising 10 samples, each, based on different ultrasound intensities (Group 1: 1.0 W/cm2; Group 2: 1.5 W/cm2) and polymethylmethacrylate bead depths (A - 2 cm; B - 3 cm) in gelatin sample. The control group comprised other nine specimens and statistically differed from the other groups. All groups irradiated with ultrasound have shown statistically significant differences in methylene blue dispersion, except for Groups 2A and 2B. Methylene blue dispersion in gelatin among groups was 1A> 1B; 2A> 1A; 2B> 1A; 2A> 1B; and 2B> 1B. Low-intensity ultrasound enabled the highest methylene blue dispersion when polymethylmethacrylate bead was positioned superficial; bead depth associated with high-intensity ultrasound did not influence methylene blue dispersion.

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The use of nanotechnology for administering drugs is a recent development that presents promising results. Therapeutic Pulsed Ultrasound (TPU) is one such therapeutic option and is widely used for treating soft tissue lesions. Thus, the objective of this study was to investigate the therapeutic effect of phonophoresis using diclofenac (DC) linked to gold nanoparticles (GNPs) in the skeletal muscle of rats used as a model of traumatic muscular injury. Wistar rats were divided into eight groups (N = 10): Sham, Muscle injury (MI), MI + TPU, MI + DC, MI + GNPs, MI + TPU + DC, MI + TPU + GNPs, and MI + TPU + DC-GNPs. The traumatic injury was performed in the gastrocnemius with a single direct traumatic impact via an injuring press. The animals received daily treatment for 5 consecutive days with TPU and gel with DC and/or GNPs. Two hours after the last treatment session, animals were euthanized and the gastrocnemius muscle surgically removed for histological and biochemical analysis. The groups exposed to some therapies (MI + TPU + DC, MI + TPU + GNPs and MI + TPU + DC-GNPs) showed reduced levels of pro-inflammatory cytokines, whereas an increase in anti-inflammatory cytokine levels was observed in the group exposed to all therapies combined (MI + TPU + DC-GNPs). Reactive species production and protein damage resulting from oxidative damage was lower for the group exposed to all tested therapies had lower production. Lower protein damage was also observed in the TPU + GNPs group. The group that underwent all tested therapies combined showed a significant increase in antioxidants compared to the MI group. During histological analysis, the MI group showed large amounts of cell infiltration and centralized nuclei, whereas the MI + TPU + DC-GNPs group showed structural improvements. Pain levels in the MI + TPU + DC-GNPs group were lower than those of the MI group. We believe that the association of TPU with DC linked to GNPs decreases the inflammation caused by traumatic muscle injury and accelerates tissue repair.

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Aim: This study was performed to assess the effect of the phonophoretic application of a nanoemulsion incorporating glucosamine and chondroitin sulfate (NANO-CG) associated with kinesiotherapy on the reduction of pain and stiffness in knee chondropathy. Materials & methods: NANO-CG was tested in vitro and in vivo prior to being applied in a randomized and controlled clinical trial. Results: Cell viability and hen's egg test-chorionallantonic membrane tests indicated the NANO-CG is safe for topical application. Permeation tests showed NANO-CG enhances drug permeation through the skin. There was no statistical significance between treated groups in this preliminary study, however, pain reduction and complete recovery of articular cartilage were observed in some patients treated with NANO-CG. Conclusion: We demonstrate that NANO-CG may be a promising candidate for the therapy of knee chondropathy.

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A copaíba (Copaifera reticulata Ducke), planta medicinal bastante usada nas regiões Norte e Nordeste do Brasil, tem difícil permeação cutânea na forma in natura, e esta permeabilidade é aumentada através do uso de nanoformulações e ainda a fonoforese, ultrassom de baixa frequência que aumenta a permeabilidade cutânea de substâncias. Sendo assim, foi analisado e comparado o efeito do óleo-resina de copaíba, in natura e de sua nanoemulsão em gel (nanogel) associado à fonoforese, na reparação muscular em ratos Wistar. Pelo método inversão de fases, formulou-se a nanoemulsão de copaíba. Esta foi incorporada ao hidrogel Carbopol® (20% nanoemulsão, 80% Carbopol®). Os animais (n = 24, machos) foram divididos em seis grupos e posteriormente foram submetidos à lesão traumática do músculo gastrocnêmio. A reparação muscular foi analisada por meio de dosagem plasmática de Aspartato Aminotransferase (AST) e Creatina Quinase (CK). Os resultados apontaram que os tratamentos de aplicação tópica do óleo-resina, de sua associação à fonoforese e desta ao nanogel foram eficazes no experimento quanto à reparação da musculatura esquelética.

Copaifera reticulata Ducke is a medicinal plants greatly employed in northern and northeastern Brazil. However, skin penetration is difficult when it is applied in natura. However, permeability increases through nanoformulations and phonophoresis and low frequency ultrasound that increases skin permeability of compounds. The effect of oil-resin of copaiba, in natura and in gel (nano-emulsion), associated to phonophoresis, was analyzed and compared for muscle repair in Wistar rats. Copaiba nano-emulsion was formulated by phase inversion. It was incorporated to hydrogel Carbopol® (20% nano-emulsion, 80% Carbopol®). Male animals (n=24) were divided into six groups and later underwent traumatic lesion of the gastrocnemius muscle. Muscle repair was analyzed by plasmatic dosage of aspartate aminotransferase (AST) and kinase creatine (CK). Results show that topic treatments with oil-resin, associated with phonophoresis and nanogel were efficient in the assay for the repair of skeleton muscles.

RESUMO

This study aimed to evaluate the effects of high-power therapeutic ultrasound in the treatment of abdominal localized adiposity in an isolated manner, with the use of neutral gel comparing ultrasonic application with 5% lipolytic active caffeine gel (phonophoresis). A total of 90 healthy women aged between 18 and 40 years were randomized and divided into two groups. The volunteers underwent anamnesis evaluation, perimetry, bioimpedance, ultrasound examination, and blood tests (complete lipidogram, creatinine, and vitamin D) before and after the end of the 10-session ultrasound protocol (3 MHz, 2 W/cm2, and 30w). Comparisons between groups and pre-post evaluation were performed by a two-way repeated-measures analysis of variance. Values of p < 0.05 indicated statistical significance. The results demonstrated a significant reduction in both groups, for the perimetry (p < 0.001) and measurements of adipose tissue thickness (p < 0.001). The examinations exhibited a significant alteration only of the complete lipidogram, but without significance (p > 0.05). When comparing the groups, no statistically significant difference was identified in any of the analyzed parameters. The high-power ultrasonic therapy is efficient in reducing localized adiposity, regardless of whether it is applied with neutral gel or 5% caffeine gel.

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The repair process consists of molecular and cellular events that can be accelerated by specific therapies. Considering this, the objective of this study was to evaluate the effects of ibuprofen phonophoresis associated with gold nanoparticles in the animal model of traumatic muscle injury. Was used 80 male wistar rats divided into eight groups: Sham; Muscle injury (MI); MI + therapeutic pulsed ultrasound (TPU); MI + Ibuprofen (IBU); MI + GNPs; MI + TPU+ IBU; MI + TPU + GNPs and MI + TPU + IBU + GNPs. The lesion in the gastrocnemius was performed by a single direct trauma impact on the injured press. The animals were treated with pulsed ultrasound and the gel with gold nanoparticles and/or ibuprofen. The treatment was applied daily for 5 days and the first session was 12 h after the muscle injury. The gastrocnemius muscle was surgically removed for analyzes biochemical, molecular and histological. In the analyzes only the MI + TPU + IBU + GNPs group showed a reduction in TNF-a and IL-1 levels, with a concomitant increase in the levels of anti-inflammatory cytokines. In the analysis of oxidative stress, only the MI + TPU + IBU + GNPs group presented a reversal of the condition when compared to the MI group. In the histological analysis, the MI group presented a large cell infiltrate and a centralized nucleus and only the MI + TPU + IBU + GNPs group showed a structural improvement, also in the pain results the MI + TPU + IBU + GNPs showed a significant difference in comparison to the MI group (p<0.01). We believe that the effects of phonophoresis with anti-inflammatory drugs associated with gold nanoparticles may potentiate the reduction of the inflammatory response and regulate the cellular redox state.

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Objetivou-se comparar a evolução da cicatrização de feridas cirúrgicas com cinco protocolos de tratamento através de análise planimétrica. Grupos de 12 ratos Wistar, foram alocados em cinco estudos experimentais: A- controle negativo; B- ferida cirúrgica, tratada com ultrassom terapêutico (UST) desligado ; C- ferida tratada somente com citrato de sildenafila ; D- ferida tratada com citrato de sildenafila e UST e grupo E-ferida tratada somente com UST. A evolução cicatricial foi acompanhada diariamente e avaliada por imagem fotográfica computadorizada aos sete, 14 e 21 dias. A aplicação do UST pulsado, com doses 1MHZ e 0,4Wcm2 reduziu o tempo de cicatrização epitelial em condições experimentais, favorecendo precocemente a reparação tecidual com efeitos qualitativos superiores ao tratamento com citrato de sildenafila (CS). A mensuração computacional para evolução da cicatrização de ferida dérmica mostrou-se um recurso de fácil aplicação sendo de baixo custo e eficiente para a aplicabilidade na rotina médica veterinária.

This study aimed at comparing the evolution of healing of surgical wounds with five treatment protocols through planimetric measurement. Groups of 12 Wistar rats were allocated in five experimental studies: A ­ negative control; B ­ surgical wound treated with therapeutic ultrasound turned off; C ­ surgical wound treated with sildenafil citrate; D ­ wound treated with sildenafil citrate and therapeutic ultrasound; and group E ­ wound treated only with therapeutic ultrasound. The healing progress was monitored daily and assessed by computed photographic image at seven, 14 and 21 days. It was concluded that the application of pulsated therapeutic ultrasound on surgical wounds at 1 MHz and 0.4Wcm2 doses reduces the epithelial healing time in experimental conditions, favoring the early repair of tissue with qualitative effects superior than the ones found in the treatment with sildenafil citrate (SC). The computational measurement for the evolution of the dermal wound healing proved to be an easy-to-apply resource, with a low cost and great efficiency for the applicability in the veterinary medical routine.

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