Copaiba Oil-Based Emulsion as a Natural Chemotherapeutic Agent for the Treatment of Bovine Mastitis: In Vivo Studies.

Copaiba oil-resin (COR) extracted from Copaifera reticulata Ducke has been used as a natural chemotherapeutic agent for a wide range of therapeutic applications. This study presents an emulgel design with a high concentration of COR, designed to prevent and treat mastitis. The COR was stabilized in a gel matrix constituted by carbopol C934P and Pluronic® F127 (ECO formulation) ratios. The permeation study of ECO was accessed by Fourier transform infrared photoacoustic spectroscopy (FTIR-PAS). The results reveal a high capacity of ECO to permeate deep skin layers. Dairy cows with a history of mastitis were used as in vivo models and exposed to ECO treatment. Monitoring of the teat's inflammatory response showed that ECO effectively prevents mastitis. Furthermore, the ECO formulation was able to form a thin film gel on the application side, preventing fly proliferation and significantly reducing the pathogen load. This study reveals a drug that can used as an alternative application for mastitis in human or veterinary clinics.

Thermosensitive gel based on cellulose derivative for topical delivery of propolis in acne treatment.

Thermosensitive bioadhesive formulations can display increased retention time, skin permeation, and improve the topical therapy of many drugs. Acne is an inflammatory process triggered by several factors like the proliferation of the bacteria Propionibacterium acnes. Aiming for a new alternative treatment with a natural source, propolis displays great potential due to its antibiotic, anti-inflammatory, and healing properties. This study describes the development of bioadhesive thermoresponsive platform with cellulose derivatives and poloxamer 407 for propolis skin delivery. Propolis ethanolic extract (PES) was added to the formulations with sodium carboxymethylcellulose (CMC) or hydroxypropyl methylcellulose (HPMC) and poloxamer 407 (Polox). The formulations were characterized as rheology, bioadhesion, and mechanical analysis. The selected formulations were investigated as in vitro propolis release, cytotoxicity, ex vivo skin permeation by Fourier Transform Infrared Photoacoustic Spectroscopy, and the activity against P. acnes. Formulations showed suitable sol-gel transition temperature, shear-thinning behavior, and texture profile. CMC presence decreased the cohesiveness and adhesiveness of formulations. Polox/HPMC/PES system displayed less cytotoxicity, modified propolis release governed by anomalous transport, skin permeation, and activity against P. acnes. These results indicate important advantages in the topical treatment of acne and suggest a potential formulation for clinical evaluation.

Human Nails Permeation of an Antifungal Candidate Hydroalcoholic Extract from the Plant Sapindus saponaria L. Rich in Saponins.

We evaluated a hydroalcoholic extract of Sapindus saponaria L. pericarps (ETHOSS), as a candidate to a topical antifungal medicine for onychomycosis. ETHOSS was produced by extracting the crushed fruits in ethanol. The saponin contents were identified and characterized by electrospray ionization mass spectrometry. We measured the in vitro antifungal activity against three dermatophyte fungi, isolated from onychomycosis: Trichophyton rubrum, T. mentagrophytes, and T. interdigitale, using broth microdilution tests. The minimum fungicide concentration of ETHOSS ranged from 195.31 to 781.25 µg/mL. The cytotoxicity of the crude extract was tested on the HeLa cell line, and its ability to permeate into healthy human nails by photoacoustic spectroscopy and Fourier transformation infrared spectrometer (FTIR) spectroscopy by attenuated total reflection. Besides its strong antifungal activity, ETHOSS showed low cytotoxicity in human cells. It was able to permeate and reach the full thickness of the nail in one hour, without the aid of facilitating vehicles, and remained there for at least 24 h. These results suggest that ETHOSS has great potential for treating onychomycosis.

Emulgels Containing Carbopol 934P and Different Vegetable Oils for Topical Propolis Delivery: Bioadhesion, Drug Release Profile, and Ex Vivo Skin Permeation Studies.

Topical administration can enable a more efficient therapy based on the improved bioavailability and patient compliance. Wounds and infections can lead to modifications of skin physiology and body protective function. Propolis (PRP) is utilized for skin protection and treatment. However, PRP extracts do not show suitable rheological characteristics and can cause irritation, pain, ulceration, and healing difficulties when they are administered on the harmed skin. Emulgels composed of Carbopol 934P (C934P) and different vegetable oils have been proposed for propolis extract release and may be a good strategy for topical delivery. The aim of this study was to investigate the bioadhesive properties, PRP release profile, skin permeation, and retention, by Franz's diffusion cell and photoacoustic spectroscopy (PS), of these emulgels. Formulations were composed of C934P and passion fruit oil (PF), sweet almond oil (SA), or andiroba oil (AO). PRP or by-product extracts were added to the systems, drug release profile was investigated, and porcine ear skin was utilized for analyses of bioadhesive properties, skin permeation, and retention. All formulations displayed similar bioadhesive force (0.05-0.07 N); PRP release was modified (prolonged), dependent on formulation composition, and mainly governed by diffusion. PS and analysis using diffusion cell showed that the systems could provide dermal permeation and retention, which was more effective for formulations containing AO. Considering the importance of propolis for many skin therapies, the emulgels containing AO for PRP delivery are worthy of biological studies and further clinical evaluation.

Mucoadhesive emulgel systems containing curcumin for oral squamous cell carcinoma treatment: From pre-formulation to cytotoxicity in tissue-engineering oral mucosa.

Current oral squamous cell carcinoma chemotherapies demonstrate off-target toxicity, which could be reduced by local delivery. Curcumin acts via many cellular targets to give anti-cancer properties; however the bioavailability is hindered by its physicochemical characteristics. The incorporation of curcumin into emulgel systems could be a promising approach for its solubilization and delivery. The aim of this work was to develop emulgel systems containing curcumin for the treatment of oral cancer. The emulgels containing curcumin were prepared with poloxamer 407, acrylic acid derivatives, oil phase (sesame oil or isopropyl myristate). The more stable system was evaluated for mechanical and rheological properties, as well as, the in vitro drug release profile, permeation and cytotoxic potential to oral mucosa models. The flow-throw system evidenced that the formulations could keep 5 min over porcine oral mucosa. Emulgel showed pseudoplastic behavior and a gelation temperature of 33 °C, which ensure their higher consistency. In addition, 70% of the incorporated curcumin was released within 24 h in an in vitro drug release study and could permeate porcine oral mucosa. Monolayers cultures and tissue-engineered models showed the selectivity of the drug and systems for tumor cells. The physicochemical properties, subsequent release and permeation of curcumin to selectivity kill cancer cells could be improved by the incorporation into emulgel systems.

Stem bark extract of Poincianella pluviosa incorporated in polymer film: Evaluation of wound healing and anti-staphylococcal activities.

Poincianella pluviosa has already been described as capable of healing skin wounds. In an attempt to prolong contact of the drug with the wound, it was proposed in this study to evaluate wound healing using a crude extract (CE) of P. pluviosa incorporated in carboxymethylcellulose polymer films. The chromatographic profile of the semipurified fraction of P. pluviosa was evaluated by ultra-high performance liquid chromatography (UHPLC), confirming the compounds gallic acid, geraniin, and ellagic acid. The films were evaluated for their physical and mechanical properties, water vapor permeability, moisture absorption capacity, and FTIR spectroscopy. For in vivo experiments, wounds were made on the back of rats and treated daily for 4, 7, 10, or 14 days with film containing CE or control film. At the end of each period, skin permeation analysis and histological analysis were made using re-epithelialisation, cell proliferation, and collagen formation. Statistical significance was determined by GraphPad Prism using t test and Mann-Whitney test. Anti-staphylococcal activity was evaluated with standard strains of Staphylococcus aureus, methicillin-resistant, and coagulase negative. It was demonstrated that the presence of CE in the films increased the capacity to absorb water and decreased resistance and permeability. The CE of the film permeated the skin, reaching the dermis and was able to influence re-epithelisation, cell proliferation, and collagen formation. Satisfactory results were observed against S. aureus strains, particularly coagulase negative. Films with CE of P. pluviosa can be an alternative in the wound healing, protecting against opportunistic infections and giving comfort to the patient.

Enhanced Cutaneous Wound Healing In Vivo by Standardized Crude Extract of Poincianella pluviosa.

Wound healing is a complex process that involves several biological events, and a delay in this process may cause economic and social problems for the patient. The search continues for new alternative treatments to aid healing, including the use of herbal medicines. Members of the genus Caesalpinia are used in traditional medicine to treat wounds. The related species Poincianella pluviosa (DC.) L.P. Queiroz increases the cell viability of keratinocytes and fibroblasts and stimulates the proliferation of keratinocytes in vitro. The crude extract (CE) from bark of P. pluviosa was evaluated in the wound-healing process in vivo, to validate the traditional use and the in vitro activity. Standardized CE was incorporated into a gel and applied on cutaneous wounds (TCEG) and compared with the formulation without CE (Control) for 4, 7, 10, or 14 days of treatment. The effects of the CE on wound re-epithelialization; cell proliferation; permeation, using photoacoustic spectroscopy (PAS); and proteins, including vascular endothelial growth factor (VEGF), superoxide dismutase 2 (SOD-2) and cyclooxygenase 2 (COX-2) were evaluated. The TCEG stimulated the migration of keratinocytes at day 4 and proliferation on the following days, with a high concentration of cells in metaphase at 7 days. Type I collagen formed more rapidly in the TCEG. PAS showed that the CE had permeated through the skin. TCEG stimulated VEGF at day 4 and SOD-2 and COX-2 at day 7. The results suggest that the CE promoted the regulation of proteins and helped to accelerate the processes involved in healing, promoting early angiogenesis. This led to an increase in the re-epithelialized surface, with significant mitotic activity. Maturation of collagen fibers was also enhanced, which may affect the resistance of the extracellular matrix. PAS indicated a correlation between the rate of diffusion and biological events during the healing process. The CE from P. pluviosa appears promising as an aid in healing.

Development and characterization of multiple emulsions for controlled release of Trichilia catigua (Catuaba) extract.

Considering the antioxidant activity of the Trichilia catigua extract (TCE), the aim of the current study was to develop and characterize W/O/W multiple emulsions containing different vegetable oils as a platform to deliver a TCE. The extract displayed antioxidant activity (IC50) of 4.59 µg/mL and total phenol content (TPC) of 50.84%. Formulations were prepared by the phase-inversion emulsification method and analyzed for morphological appearance, pH, conductivity, droplet size and distribution, content of active, rheological properties, in vitro release, skin permeation, and stability. Formulations prepared with canola oil were selected and displayed regular morphology, mean diameter 2.77 µm (without TCE), 3.07 µm with 0.5% and 3.23 µm with 1.0% TCE. Rheometry (flow) showed pseudoplastic behavior with minimal thixotropy for both systems. TCE could be released from emulsions containing 1.0% and 0.5% TCE in a controlled manner for 16 and 23 h, respectively. The emulsions allowed good retention of TCE in the skin (stratum corneum, epidermis, and dermis). In a 180-d assessment of accelerated chemical stability, TPC was more reduced for the emulsions at 40 °C; other parameters remained stable. Multiple emulsions containing TCE were developed, exhibited good characteristics, and may be considered for future investigations as anti-aging formulations for the skin.

Employing photoacoustic spectroscopy in the evaluation of the skin permeation profile of emulsion containing antioxidant phenolic-rich extract of Melochia arenosa.

CONTEXT: Oxidative stress is an important factor modulating skin alterations. Melochia arenosa Benth. (Malvaceae) is a Brazilian plant with antimicrobial activity and antioxidant potential. OBJECTIVE: The objective of this study is to develop a topical formulation containing antioxidant phenolic-rich extract of M. arenosa and to evaluate its skin permeation profile. MATERIALS AND METHODS: Response surface methodology was used to maximize the total phenolic (TP) content of the extract and its antioxidant activity was evaluated by 2,2-diphenyl-1-picryl-hydrazyl (DPPH), 2,2'-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and respiratory burst methods. An emulsion containing 1% optimized extract (OE) was developed and employed photoacoustic spectroscopy (PAS) for the determination of its skin permeation profile. The morphology of the skin was studied in histological sections stained with hematoxylin-eosin. RESULTS AND DISCUSSION: The optimum conditions predicted for the major extractive efficiency of the phenolics with 100% ethanol led extraction time 101 h and plant:solvent proportion 1:13.5 (w/v). OE presented TP = 724.6 ± 8.2 mg GAE/g extract and scavenging capacity of DPPH (IC50 value = 11.43 ± 0.14 µg/mL) and ABTS radicals (IC50 value = 35.42 ± 0.48 µg/mL). The production of ROS by neutrophils after stimulation with phorbol miristate acetate was lower when the OE was present in the reaction medium, endorsing its high antioxidant capacity. The data obtained by PAS indicated that the OE present in the emulsion has permeated and was distributed in the whole skin. No histopathological alterations were observed in the histological analysis. CONCLUSION: The formulation developed is a promising tool for skin care and could prevent the damage caused by oxidative stress.

Stryphnodendron adstringens: Clarifying Wound Healing in Streptozotocin-Induced Diabetic Rats.

Diabetes mellitus is a serious public health problem in which a major complication is impaired wound healing. Among the strategies developed to foster tissue repair is the use of medicinal plants. The bark of Stryphnodendron adstringens, which is popularly used as an aid in wound healing, has a documented effect on wound repair in normal rats. This study evaluated the healing action of the crude extract of S. adstringens in diabetic rats, and its chemical content. Compounds present in the crude extract were characterized by mass spectrometry. In diabetic rats (streptozotocin 35 mg/kg), two wounds made in the skin were treated daily for 4, 7, 10, and 14 days with gel containing 1 % crude extract or with base gel. Histological analyses involved the measurement of the length and thickness of the re-epithelialized surface, quantification of the number of cells in mitosis, and types I and III collagen fibers. Also, cutaneous permeation by photoacoustic spectroscopy, and the expression of cyclooxygenase-2 and vascular endothelial growth factor by Western blot were assessed. The crude extract fingerprint showed masses indicating proanthocyanidins. The crude extract mainly stimulated cell migration and proliferation of keratinocytes at the beginning of the treatment in addition to stimulating the replacement of type III collagen fibers by type I collagen fibers at 10 and 14 days. The photoacoustic spectroscopy technique showed that the gel containing 1 % of crude extract permeated through the skin to the dermis, where the crude extract was found. Vascular endothelial growth factor was stimulated after 7 days of treatment with the crude extract and cyclooxygenase-2 at 4, 7, and 10 days. The crude extract of S. adstringens acted in tissue repair in wounds in diabetic rats by stimulating the production of collagen fibers at the wound site. The crude extract favored the formation of a more organized extracellular matrix and filled the entire extent of the wound, and also fostered the upregulation of cyclooxygenase-2 and vascular endothelial growth factor, which are essential to this process. These crude extract actions in diabetic wounds are probably due to the presence of proanthocyanidins.

Desenvolvendo o paradigma da integralidade no cuidado à saúde no PETSaúde/UEM: relato de experiência: atuação de maneira articulada no cuidado integral à saúde da comunidade / Developing the paradigm of Comprehensiveness in health care in PETSaúde/UEM: experience report: acting in a manner articulated in the integrated community health care

O curso de Odontologia da UEM iniciou sua participação no Projeto PET-Saúde a partir da Portaria Interministerial N.º 3, de 7 de maio de 2009. Atualmente, o programa conta com cinco grupos tutoriais, incluindo seis cursos do Centro de Ciências da Saúde (CCS) e um do Departamento de Psicologia. O objetivo deste trabalho é relatar a experiência do grupo tutorial vinculado à UBS Mandacaru, em Maringá ­ PR, que no ano de 2013 trabalhou com o tema "Fortalecimento da Rede Mãe Paranaense no município de Maringá-PR". A dinâmica de trabalho foi dividida em: Abordagem do tema por meio de oficinas sobre o PETSaúde e a Rede Mãe Paranaense e a realização de palestras e oficinas sobre aleitamento materno. Foi realizada uma pesquisa ajustada à realidade local, além de visitas à UBS e a participação no grupo de apoio às gestantes. A aprendizagem ativa com análise crítica do serviço foi exercida por meio da participação no Conselho Municipal e Local de Saúde. As atividades mostraram que o trabalho individual não supre as necessidades da população, mas sim, um trabalho em equipe. Uma equipe multiprofissional que atue de maneira articulada ao cuidado integral à saúde dos indivíduos. O PET-Saúde possibilita ao aluno aprender a direcionar as ações baseadas na autonomia e corresponsabilidade, bem como adquirir liderança para levar adiante o compromisso com o bem-estar da população (AU).

The course of Dentistry UEM began its participation in Project PET-Saúde from the Ministerial Ordinance No. 3 of May 7, 2009. Today the program has 5 tutorial groups , including 5 courses at the Center for Health Sciences ( CCS ) and 1 Department of Psychology . The aim of this study was to report the experience of the tutorial group linked to UBS Mandacaru in Maringá - PR , who worked with the theme "Strengthening Mother Network Paranaense in Maringá - PR ". Dynamics of work was divided into: Addressing the issue through workshops on PET - Saúde and Mother Rede Paranaense and lectures and workshops on breastfeeding. The survey was adjusted to local realities, prioritizing the teaching-service integration with UBS visits and participation in support group for pregnant women. The active learning through critical analysis of services, through participation in the Municipal Local Health Board, was also performed. This project has shown that individual work does not meet the needs of the population, but rather a team effort. A multidisciplinary team that acts in coordination in comprehensive health care to individual. The PET-Saúde allows the student to learn how to drive actions based on autonomy and responsibility as well as acquire leadership to carry forward the commitment to the welfare of the population (AU).

Antifungal activity and nail permeation of nail lacquer containing Piper regnellii (Miq.) C. CD. var. pallescens (C. DC.) Yunck (Piperaceae) leave extracts and derivatives.

The dermatophytes are filamentous fungi that cause cutaneous fungal infections because they use keratin as a nutrient source. For this study the antidermatophyte activity of the extracts and derivates from leaves of Piper regnellii was analyzed. From the dichloromethane extract (EBD) neolignans such as eupomatenoid-3 and eupomatenoid-5 were obtained, and it was submitted to fractionation to remove the green residue, designated as the chloroform fraction (FF). Extracts, chloroform fraction and compounds were tested against Trichophyton rubrum ATCC 28189 to determine the minimum inhibitory concentration (MIC). The chloroform fraction was incorporated to nail lacquer that was analyzed by photoacoustic spectroscopy, in vitro assay and scanning electronic microscopy. For antifungal activity in solid medium the dichloromethane extract and chloroform fraction were used. The compounds eupomatenoid-3 and eupomatenoid-5 were less active than the dichloromethane extract against T. rubrum. EBD and FF showed moderate activity in hyphal growth inhibition in solid medium and EBD did not link to ergosterol. Nail lacquer containing the chloroform fraction showed good penetration through the nail as determined by photoacoustic spectroscopy. From in vitro studies it was observed that nail lacquer concentrations above 20 mg/mL prevented the growth of fungi, but concentrations up to 2.5 inhibited the growth. Scanning electronic microscopy was used to confirm the in vitro nail lacquer activity results. The specie P. regnellii showed great antifungal activity against T. rubrum, and nail lacquer containing its chloroform fraction has great potential to treat onychomycosis caused by these microorganisms.

Percutaneous penetration, melanin activation and toxicity evaluation of a phytotherapic formulation for vitiligo therapeutic.

The aim of this work was to apply photoacoustic spectroscopy for the ex vivo determination of the penetration rate of a phytotherapic formulation for vitiligo therapeutic, with or without salicylic acid as the promoter agent. In addition, the compound toxicity and morphophysiology effects were evaluated for different concentrations of salicylic acid. The experiments were performed as a function of the period of time of treatment in a well-controlled group of rabbits. Toxic effects were not observed with any of the tested products. All formulations containing salicylic acid induced cutaneous reaction which was dose dependent. The histological analysis showed that the use of the medication was associated with an increased comedogenic effect in relation to the control group, regardless of salicylic acid concentration. Inflammatory reactions and acanthosis were observed only in the animals treated with formulations containing higher concentrations of salicylic acid, while none of these effects were detected with the use of the formulation containing 2.5% (wt/vol) of salicylic acid. Photoacoustic depth monitoring showed that both formulations, with or without salicylic acid, propagated through the skin up to the melanocytes region, suggesting that the transport of the active agent may occur through the epithelial structure without the need of using queratinolitic substances, which are known to induce side effects in the animals.