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Clinicopathological features and chemotherapy can influence the quality of life (QOL), women with ovarian cancer. This study aimed to evaluate the physical and functional well-being, and ovarian cancer-specific effects scores reported from QOL questionnaire among women with ovarian cancer at the time of in their initial diagnosis and access the scores trajectory of women receiving neoadjuvant and adjuvant chemotherapy. This prospective study used cross-sectional analysis at baseline and longitudinal analysis from baseline to 12-month post-chemotherapy. QOL was evaluated at the baseline, at sixth cycle and 12-month post-chemotherapy using FACT-O questionnaire. Clinicopathological features and chemotherapy regime were evaluated and tested for associations with QOL measures. Of the 38 women enrolled in this study, 27 (80.1%) completed the questionnaire for 12 months. The multivariate linear regression results suggest, at the baseline, women with advance stage and presence of post-surgery residual disease showed lower scores in physical and functional well-being, ovarian cancer-specific effects, and FACT-O TOI domains (p

The effect of nanoencapsulation on the in vitro photoprotection and antioxidant properties of blueberry (Vaccinium myrtillus) extract, before and after their dispersion into an oil-in-water emulsion and its final stability under stress conditions. Besides its skin healing activity, chitosan was chosen as wall material due to its natural origin, and possibility of obtention from shrimp residues. Chitosan/tripolyphosphate (TPP) nanoparticles loaded with blueberry extract were produced and characterized. Three different semi-solid oil-in-water emulsions, using Ecocert certified materials, were developed containing, respectively, (i) 5% (wt/wt) of extract-free nanoparticles, (ii) 5% (wt/wt) of extract-loaded nanoparticles, (iii) 2% (wt/wt) of free extract. Sun protection factor (SPF), antioxidant activity and stability under stress conditions were evaluated. The concentration of rutin was determined by High Performance Liquid Chromatography (HPLC). The loading of blueberry extract into nanoparticles kept their physicochemical properties, as well as SPF and antioxidant activity, over the course of the stability study. Extract-loaded nanoparticles were dispersed in a semi-solid oil-in-water emulsion and were shown to protect the extract from oxidation, suggesting that formulation containing 5% (wt/wt) of extract-free nanoparticles could presented lower difference between initial and final SPF and antioxidant activity values after 90 days of analysis. The developed formulation is proposed as a greener potential formulation to be used as photoprotector, especially if associated with physical sun filters. The role of blueberry flavonoids and the synergistic effect of nanoparticles against skin aging are here discussed., This research was funded by FAPESP (grant number 2015/25533–7, 2017/14757–7, 2017/05275–9) and in part by CAPES (Finance Code 001). This study was financed by CNPq (301436/2017–7) granted to PGM, and by the Portuguese Science and Technology Foundation (FCT / MCT) and from European Funds (PRODER/COMPETE) under the project reference UIDB/04469/2020 (strategic fund), co-financed by FEDER, under the Partnership Agreement PT2020, granted to EBS., info:eu-repo/semantics/publishedVersion

Journal pre-proofs, Curcumin (CUR) is a phenolic compound present in some herbs, including Curcuma longa Linn. (turmeric rhizome), with a high bioactive capacity and characteristic yellow color. It is mainly used as a spice, although it has been found that CUR has interesting pharmaceutical properties, acting as a natural antioxidant, anti-inflammatory, antimicrobial, and antitumoral agent. Nonetheless, CUR is a hydrophobic compound with low water solubility, poor chemical stability, and fast metabolism, limiting its use as a pharmacological compound. Smart drug delivery systems (DDS) have been used to overcome its low bioavailability and improve its stability. The current work overviews the literature from the past 10 years on the encapsulation of CUR in nanostructured systems, such as micelles, liposomes, niosomes, nanoemulsions, hydrogels, and nanocomplexes, emphasizing its use and ability in cancer therapy. The studies highlighted in this review have shown that these nanoformulations achieved higher solubility, improved tumor cytotoxicity, prolonged CUR release, and reduced side effects, among other interesting advantages., This study was funded by the Coordination for Higher Level Graduate Improvements (CAPES/Brazil, finance code 001), National Council for Scientific and Technological Development (CNPq/Brazil, PIBIC process #123483/2020-4), State of São Paulo Research Foundation (FAPESP/Brazil, processes #2017/10789-1, #2018/10799-0, #2018/06475-4, #2018/07707-6, #2019/08549-8, and #2020/03727-2). This work was also supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UIDB/04469/2020 unit and the project AgriFood XXI (NORTE-01-0145-FEDER-000041) funded by the European Regional Development Fund under the scope of Norte2020 - Programa Operacional Regional do Norte. Our Figures were created with BioRender, info:eu-repo/semantics/publishedVersion

To evaluate adherence to oral hormone therapy (HT) and which factors impact in incomplete adherence and quality of life. This was a cross-sectional study. Setting: Women’s Hospital Prof. Dr. Jose Aristodemo Pinotti. Participants: women with breast cancer under treatment with oral HT. Main outcome measures: interview and performed an adherence questionnaire (Morisky–Green) and two questionnaires of quality of life (EORTC-QLQ30/BR23). The interviews were done once in a 5-month period. Fifty-eight women were interviewed: 42 under treatment with tamoxifen (TX) and 16 under treatment with aromatase inhibitor (AI). Twenty-six women (44%) showed high adherence to the treatment, 31 (54%) medium adherence, and 1 (2%) low adherence. Statistical analysis showed a relation between incomplete adherence and systemic therapy side effects as well as higher stages of disease, with no difference between the two drugs. When treatments were compared, this study showed treatment with AI presented less breast symptoms and better role functioning. Quality of life score was high, compared to the reference value. A low percentage of women with breast cancer were highly adherent to HT treatment. Low/medium adherence was associated with higher stages of disease and systemic side effects. Quality of life had high scores, with better role function and less breast symptoms in women being treated with an AI.

PURPOSE. Topical therapy of local disease (e.g. skin) is advantageous over oral therapy since there is less systemic drug distribution (so fewer side-effects), no first-pass effect, etc. However, patient compliance with topical therapy can be poor as it may require many applications a day and can last months. Here we propose a topical controlled release formulation with thermoresponsive gelation at body temperature and improved adhesiveness, making it easier to remain in contact with the body. METHODS. The formulation contains two excipients, poloxamer 407 (P407) and casein. Casein can modify the properties of the hydrogel through molecular entanglement. In addition, tissue reaction and drug release profile were evaluated. RESULTS. Changes in casein concentration affected adhesive strength, viscosity, mechanical properties and drug release, presumably by hydrophobic interactions between casein and P407. Two different concentrations of P407 were tested with two different concentrations of casein. Formulations containing 5% and 10% casein released 80% of model drug in 48h, while formulations without casein released the same fraction in around 24h hours. Formulations with 10% casein had almost twice the adhesive strength of those without casein. CONCLUSIONS. Addition of casein modified the mechanical properties and drug release rate of the hydrogel. There was no inflammation or injury after brief exposure in vivo.

The objective of the present study is to observe the frequency and severity of urinary symptoms in women with breast cancer (BC) being treated with oral hormone therapy, associating them to drug adherence. The participants were interviewed once from June to October 2016. The evaluation of urinary symptoms was performed by two questionnaires: International Consultation on Incontinence Questionnaire - Short Form (ICIQ-SF) and International Consultation on Incontinence Questionnaire Overactive Bladder Module (ICIQ-OAB). Adherence was evaluated by the Morisky-Green method. Statistical analysis was performed by the Mann-Whitney test, linear regression, and Spearman correlation. Fifty-eight women were interviewed: 42 treated with tamoxifen and 16 with aromatase inhibitor. Twenty-seven women (46.5%) presented urinary incontinence symptoms and 15 (25.8%) presented stress urinary incontinence (SUI). Fourteen (24.1%) women had symptoms of overactive bladder (OAB). There was no statistical difference in symptoms between both treatments and duration of treatments. Higher scores in the ICIQ-SF questionnaire were associated with low/medium adherence and advanced age. Higher scores in the ICIQ-OAB questionnaire were associated with low/medium adherence. The present study showed a high prevalence of urinary symptoms, such as urinary incontinence and OAB, associated with low/medium adherence and older age in women with BC being treated with oral hormone therapy. Health professionals should be alert to these symptoms since it could influence life quality and adherence to treatment. O objetivo do presente estudo foi observar a frequência e a gravidade dos sintomas urinários em mulheres com câncer de mama em uso de terapia hormonal oral, associando estes com a adesão ao tratamento. MéTODOS: As pacientes foram entrevistadas uma única vez, entre junho e outubro de 2016. A avaliação dos sintomas urinários foi realizada por dois questionários: International Consultation on Incontinence Questionnaire - Short Form (ICIQ-SF, na sigla em inglês) e o Questionário Sobre Bexiga Hiperativa (ICIQ-OAB, na sigla em inglês). A adesão foi avaliada pelo método Morisky-Green. A análise estatística foi realizada pelo teste de Mann-Whitney, regressão linear e correlação de Spearman. Foram entrevistadas 58 mulheres: 42 tratadas com tamoxifeno e 16 com inibidor de aromatase. Vinte e sete mulheres (46,5%) apresentaram sintomas de incontinência urinária (IU) e 15 (25,8%) apresentaram incontinência urinária por estresse (IUS). Quatorze (24,1%) das mulheres tinham sintomas de bexiga hiperativa. Não houve diferença estatística nos sintomas entre os tratamentos e a duração dos tratamentos. Os escores mais elevados no questionário ICIQ-SF estiveram associados à baixa/média adesão e à idade avançada. Os escores mais elevados no questionário da ICIQ-OAB foram associados à baixa/média adesão. CONCLUSãO: O presente estudo mostrou alta prevalência de sintomas urinários, como IU e bexiga hiperativa, associadas à baixa/média adesão e à idade mais avançada em mulheres com câncer de mama em tratamento com hormonioterapia oral. Os profissionais de saúde devem estar atentos a esses sintomas, pois eles podem influenciar a qualidade de vida e a adesão ao tratamento.

Consumers are attracted to the latest fashion trends and different looks. This drives the search for novel hair treatments. Some chemicals present in hair treatment products can penetrate the hair shaft. These materials can either nourish or injure the hair cortex. Different techniques have been used to investigate the mechanism of molecule penetration and the conditions under which penetration occurs. This article reviews the techniques applied for this purpose. Various microscopy techniques are used to capture clear and colourful images to determine the diffusion pathways and the exact location of the molecules under study. However, the laborious sample preparation often leads to sample destruction since cross-sectioning is often required. While various other techniques have been successfully used for investigating the penetration methods, most of these require different amounts of work to be put in for sample preparation and instrumentation. Several spectroscopic techniques have been used to study the penetration of the molecules because of the high levels of accuracy and the quick response time of these techniques. Moreover, the samples are not damaged during the investigation.Les consommateurs sont attirés par les dernières tendances et les différents styles de la mode. Cela stimule la recherche pour de nouveaux traitements capillaires. Certains produits chimiques présents dans les produits de soins capillaires peuvent pénétrer la tige du cheveu. Ils peuvent tantôt nourrir, tantôt endommager le cortex pileux. Différentes techniques ont été utilisées pour étudier le mécanisme de pénétration des molécules et les conditions dans lesquelles cette pénétration a lieu. Cet article examine les techniques appliquées à cette fin. Diverses techniques de microscopie sont mises en œuvre pour capturer des images claires et colorées afin de déterminer les voies de diffusion et la localisation exacte des molécules à l’étude. Cependant, la préparation laborieuse des échantillons conduit fréquemment à la destruction des échantillons, car une coupe transversale est souvent exigée. Si plusieurs autres techniques ont été utilisées avec succès pour étudier les méthodes de pénétration, la plupart d’entre elles nécessitent différents niveaux d’activité à mettre en œuvre pour la préparation des échantillons et l’instrumentation. Plusieurs techniques spectroscopiques ont été utilisées pour étudier la pénétration des molécules en raison de leurs niveaux élevés de précision et de leur délai de réponse rapide. De plus, les échantillons ne sont pas endommagés pendant l’investigation.

Cachexia, a severe multifactorial condition that is underestimated and unrecognized in patients, is characterized by continuous muscle mass loss that leads to progressive functional impairment, while nutritional support cannot completely reverse this clinical condition. There is a strong need for more effective and targeted therapies for cachexia patients. There is a need for drugs that act on cachexia as a distinct and treatable condition to prevent or reverse excess catabolism and inflammation. Due to ghrelin properties, it has been studied in the cachexia and other treatments in a growing number of works. However, in the body, exogenous ghrelin is subject to very rapid degradation. In this context, the intranasal release of ghrelin-loaded liposomes to cross the blood-brain barrier and the release of the drug into the central nervous system may be a promising alternative to improve its bioavailability. The administration of nose-to-brain liposomes for the management of cachexia was addressed only in a limited number of published works. This review focuses on the discussion of the pathophysiology of cachexia, synthesis and physiological effects of ghrelin and the potential treatment of the diseased using ghrelin-loaded liposomes through the nose-to-brain route., Funded by PROSUP/Coordination of Superior Level Staff Improvement (CAPES), University of Sorocaba (UNISO), São Paulo Research Foundation (FAPESP/2014/50928-2), Brazil, granted to MVC, and by the Portuguese Science and Technology Foundation (FCT/MCT) and from European Funds (PRODER/COMPETE), co-financed by FEDER, under the Partnership Agreement PT2020 granted to EBS (UIDB/04469/2020 (strategic fund), info:eu-repo/semantics/publishedVersion

Topical application is an important administration route for drugs requiring local action on the skin, thereby avoiding their systemic absorption and adverse side effects. Rosmarinus officinalis L. (syn. Salvia rosmarinus Spenn.), popularly known as rosemary, is an aromatic plant with needle-like leaves belonging to the Lamiaceae family. Rosemary has therapeutic properties and has been used in the folk medicine, pharmaceutical, and cosmetics industries, mainly for its antioxidant and anti-inflammatory properties, which are attributed to the presence of carnosol/carnosic and ursolic acids. The therapeutic use of rosemary has been explored for the treatment of inflammatory diseases; however, other uses have been studied, such as wound healing and skin cancer and mycoses treatments, among others. Besides it therapeutic uses, rosemary has potential applications in cosmetic formulations and in the treatment of pathological and non-pathological conditions, such as cellulite, alopecia, ultraviolet damage, and aging. This review aims to critically discuss the topical applications of rosemary found in the literature while also offering relevant information for the development of topical formulations of its bioactive compounds., This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brasil (CAPES)—Finance Code 001. Eliana B. Souto acknowledges the financial support received from Portuguese Science and Technology Foundation (FCT/MCT) and from European Funds (PRODER/COMPETE) forunder the projects reference M-ERA-NET/0004/2015-PAIRED and and UIDB/04469/2020 (strategic fund), co-financed by FEDER, under the Partnership Agreement PT2020., info:eu-repo/semantics/publishedVersion

Nature has been a source of medicinal treatments for thousands of years, with the use of plants as prototypes for drug development and for the extraction of active compounds. Skin injuries occur regularly in everyday life, and the human skin has the ability to promote repair spontaneously under healthy conditions. However, some intrinsic and external factors may interfere with skins' natural ability, leading to nonhealing lesions and chronic wounds, which directly affect health and quality of life. Thus, attention should be given to this health problem, using an appropriated management when necessary. In this scenario, phytotherapy may be an option for cutaneous wound treatment, although further high-quality studies are needed to firmly establish the clinical efficacy of plants. This article reviews traditionally used natural actives for wound healing, highlighting their characteristics and mode of action.

The aim of the present study was to carry out stability tests and in vitro sun protection factor (SPF) evaluations of formulations containing free or microencapsulated chemical sun filters to improve their use. To this end, three formulations were developed and subjected to stability studies. The most stable formulation was chosen as a vehicle for free and microencapsulated chemical sun filters, and subjected to further stability studies and in vitro SPF assays. The SPF values were approximately 12 and 11 for formulations containing free and encapsulated sun filters, respectively, and both types were stable under stress. Chemical sun filters can be microencapsulated, which may aid in generating innovative sunscreen formulations.

Introduction In the pregnancy-puerperal cycle, women may develop complications that require admission to the Intensive Care Unit (ICU). Thus, special attention to pharmacotherapy is necessary, particularly to potential drug interactions (PDIs) and to the effect of the drugs on the fetus and newborn. Objective The aim of this study was to determine the profile of PDIs and the potential risk of drugs used during pregnancy and breastfeeding among patients admitted to the ICU. Methods We conducted an observational, cross-sectional and prospective study, including pregnant and breastfeeding women admitted to the ICU at the Women's Hospital of a university in the city of Campinas, Brazil, for one year. Online databases were used to identify and classify the PDIs and the potential risk of the drugs used during pregnancy and breastfeeding. Results We evaluated 305 prescriptions of 58 women, 31 pregnant and 27 breastfeeding, and 284 (91%) prescriptions presented PDIs. A total of 175 different combinations of PDIs were identified in the prescriptions, and adverse effects caused by the simultaneous use of drugs were not actually observed in the clinical practice. A total of 26 (1.4%) PDIs were classified as contraindicated. We identified 15 (13.8%) drugs prescribed with risk D, and 2 (1.8%) with risk X for pregnant women, as well as 4 (4.9%) drugs prescribed with high risk for breastfeeding women. Conclusions This study demonstrates that there is a high incidence of PDIs in prescriptions. Most drugs used by pregnant and breastfeeding women at the ICU did not present serious risks to their fetus and newborns, but sometimes drugs with risk D or X are necessary in the course of the treatment. Introducao No ciclo gravidico-puerperal, as mulheres podem desenvolver complicacoes que necessitam de internacao na Unidade de Terapia Intensiva (UTI). Assim, e necessaria uma atencao especial a farmacoterapia, particularmente as interacoes medicamentosas potenciais (IMPs) e ao risco dos medicamentos para o feto e o recem-nascido. Objetivo Determinar o perfil das IMPs e o risco potencial dos medicamentos utilizados durante a gravidez e a amamentacao entre as mulheres internadas em UTI. Metodos Foi realizado um corte transversal e prospectivo, observacional, incluindo mulheres gravidas e lactantes internadas na UTI do Hospital da Mulher de uma universidade de Campinas durante um ano. Bases de dados online foram usadas para identificar e classificar as IMPs e o potencial risco de uso de medicamentos durante a gravidez e a amamentacao. Resultados Foram avaliadas 305 prescricoes de 58 mulheres, 31 gravidas e 27 lactantes, e 284 (91%) prescricoes apresentaram IMPs, sendo que 175 combinacoes diferentes de IMPs foram identificadas nas prescricoes, e nao foram observados efeitos nocivos pelo uso concomitante dos medicamentos na pratica clinica. Um total de 26 (1,4%) IMPs foram classificadas como contraindicadas. Foram identificados 15 (13,8%) medicamentos prescritos com risco D, e 2 (1,8%) com risco X para mulheres gravidas, e foram identificados 4 (4,9%) medicamentos prescritos como de alto risco para as mulheres que estavam amamentando. Conclusoes Este estudo demonstra que ha uma alta incidencia de IMPs nas prescricoes. A maioria dos medicamentos utilizados por mulheres gravidas e lactantes em UTI nao apresentou serios riscos para o feto e o recem-nascido, mas as vezes sao necessarios medicamentos categorizados como risco D ou X.

This study examines whether women with breast cancer, who are adherent and non-adherent to tamoxifen, differ in their perceptions of information received during treatment. This cross-sectional study included women receiving tamoxifen as adjuvant treatment for breast cancer recruited from a teaching hospital specialised in women’s health in the state of São Paulo (Brazil). Women were interviewed and their records were reviewed for socio demographic data and clinical characteristics. We assessed tamoxifen adherence using the Morisky-Green Test, and the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire – Information module (EORTC QLQ-INFO25) was used to evaluate the information received by the women. The sample contained 31 women (mean age = 55.4; SD = 11.6 years). According to the Morisky-Green Test, 74.2% of the women had suboptimal tamoxifen adherence. The global score for women’s perceptions of information they received about the treatment and disease was 57.0 ±19.1 on a scale of 0 to 100, and no significant differences in scores were observed between adherents and non-adherents. A high prevalence of suboptimal tamoxifen adherence was observed. We found no significant differences between women with breast cancer who were adherent and non-adherent to tamoxifen.

The aim of this study was to develop a phytocosmetic sunscreen emulsion with antioxidant effect, containing a blend of flavonoid-enriched plant extracts. In vitro sun protection factor, antioxidant activity, skin irritation, photostability, cutaneous permeation, and retention of flavonoids were evaluated. Thermodynamically stable emulsions were obtained and tested for sensorial analysis after loading the blend of extracts. The selected emulsion was stable when stored at low temperatures (5 C), for which after 120 days the concentration of quercetin and rutin were above their limit of quantification, i.e., 2.8 &plusmn, 0.39 &micro, g/mL and 30.39 &plusmn, g/mL, respectively. Spreadability, low rupture strength and adhesiveness were shown to be similar to a conventional topical product. Higher brittleness, pseudo-plastic, and viscoelastic behaviors were also recorded for the developed phytocosmetic sunscreen. The product presented a critical wavelength of 387.0 nm and ultraviolet rays A and B (UVA/UVB) rate of 0.78, confirming that the developed formulation shows capacity for UVA/UVB protection, protecting skin against damages caused by Ultraviolet (UV) radiation. Rutin was shown to permeate the skin barrier and was also quantified in the stratum corneum (3.27 &plusmn, 1.92 &micro, g/mL) by tape stripping and retention test (114.68 &plusmn, 8.70 &micro, g/mL). The developed flavonoid-enriched phytocosmetic was shown to be non-irritant to skin by an in vitro assay. Our results confirm the antioxidant activity, sun protection, and physical properties of the developed phytocosmetic for topical application.

The aim of study was to determine the in vitro sun protection factor (SPF) and the photostability profile of a topical formulation composed of nanoparticles loaded with vegetable extracts and to assess its physicochemical properties. Chitosan/tripolyphosphate (TPP) nanoparticles loaded with flavonoids-enriched vegetable extracts (Ginkgo biloba L., Dimorphandra mollis Benth, Ruta graveolens, and Vitis vinifera L.) were produced and characterized for their morphology, mean particle size, zeta potential, and encapsulation efficiency. A final topical formulation was obtained by dispersing chitosan/TPP nanoparticles in an o/w emulsion. Results showed that nanoparticles dispersion exhibited yellowish color, spherical shape, and uniform appearance. Extract-loaded chitosan/TPP nanoparticles showed a mean particle size of 557.11±3.1 nm, polydispersity index of 0.39±0.27, zeta potential of +11.54±2.1 mV, and encapsulation efficiency of 75.89% of rutin. The recorded texture parameters confirm that the developed formulation is appropriate for skin application. The SPF obtained was 2.3±0.4, with a critical wavelength of 387.0 nm and 0.69 UVA/UVB ratio. The developed formulation exhibited photostability, allowing the release of flavonoids from nanoparticles while retaining rutin into the skin in a higher extension., The authors acknowledge FAPESP (grant number 2015/25533-7 and 2017/14757-7), CAPES, and CNPq agencies for the financial support of this study. The authors also acknowledge the financial support received from the Portuguese Science and Technology Foundation (FCT/MCT) and from the European Funds (PRODER/COMPETE) under the project reference M-ERA-NET/0004/2015-PAIRED, co-financed by FEDER, under the Partnership Agreement PT2020., info:eu-repo/semantics/publishedVersion

The aim of this study was to validate a HPLC method for the assay of flavonoids in extracts obtained from natural sources, i.e., from Dirmophandra mollis Benth, Ginkgo biloba L., Ruta graveolens L., and Vitis vin&iacute, fera L. The potential sun protecting effect, antioxidant activity, and cell viability of the extracts were also determined. Individual extracts (obtained from each individual species) and a mixed extract (containing the four extracts) were analyzed by the validated HPLC method for the identification of flavonoids and quantification of rutin and quercetin. An in vitro cell viability study was carried out using the neutral red method. The in vitro sun protection factor was determined by spectral transmittance and in vitro antioxidant efficacy was evaluated against DPPH, ABTS, and AAPH radicals. The HPLC method used for the identification and quantification of flavonoids in extracts exhibited linearity, precision, accuracy, and robustness. Detection and quantification limits were, respectively, 2.881 &plusmn, 0.9 &mu, g&middot, mL&minus, 1 and 0.864 &plusmn, 1 for quercetin, and 30.09 &plusmn, 1 &mu, 1 and 9.027 &plusmn, 1.1 &mu, 1 for rutin. All extracts did not affect cell viability at the evaluated concentration range and exhibited a sun protection effect and antioxidant activity. Among the evaluated extracts, Ginkgo biloba L. and the mixed extract depicted the most expressive antioxidant activity. The mixed extract exhibited sunscreen protection against ultraviolet A (UVA) and ultraviolet B (UVB) and a critical wavelength of 372.7 &plusmn, 0.1. Our results translate the enhanced flavonoids&rsquo, composition of the mixed extract, which may be a potential alternative over sunscreens and antioxidants in pharmaceutic/cosmetic formulations.

In this paper, hydrogels were prepared by copolymerization of acrylamide (AAm) with PVA and PEG to study the incorporation and release of bromelain. The association of bromelain with polyvinyl alcohol (PVA) or polyethylene glycol (PEG) in a hydrogel for controlled release has potential for burns noninvasive treatment and topical inflammatory occurrences. Total protein concentration and bromelain enzymatic activity was determined by Bradford and azocasein assay methods, respectively. Bro-PVA-co-AAm (bromelain loaded PVA hydrogels) incorporated 42.5 mg and 23.1 U, corresponding to 91.3% and 88.9%, respectively of protein content and enzymatic activity; while PEG hydrogels incorporated 41.4 mg and 16.0 U, corresponding to 88.9% and 53.8%, respectively. PVA and PEG hydrogels released less than 5% of the incorporated protein content after 24 h of study. However, release in terms of enzymatic activity reached 60% (Bro-PVA-co-AAm hydrogel) and 100% (Bro-PEG-co-AAm hydrogel). The joint analysis of hydrogels mechanical properties indicated that bromelain-loaded PVA hydrogels have more structural compatibility to biological conditions, due to a complex molecular architecture, with a lightweight, mucoadhesive, strong and soft constitution. Also, PVA-co-AAm synthesized hydrogels are able to absorb and release bromelain, indicating their potential use in a modified protein release system.

Bromelain has many therapeutic properties including wound healing and blood circulation improvement. However, bromelain is usually unstable and suffers autolysis, which results in a decrease of enzymatic activity and limited applications. Encapsulation of bromelain in nanoparticles can diminish degradation by protease immobilization, which may increase its stability and efficacy. The natural polymer chitosan can be nanostructured and trap the enzyme, maintaining the claims of biocompatibility, biodegradability and natural source of the formulation ingredients. Considering the above, chitosan-bromelain nanoparticles (C-B-NP) were produced by ionic crosslinking and presented spherical shape (electron microscopy) of 100.9 ± 0.5 nm and polydispersity index of 0.222 ± 0.012 (dynamic light scattering). Encapsulation efficiency was calculated as 85.1 ± 1% with regard to enzymatic activity, and C-B-NP presented 4.9 U/mL of enzymatic activity, which corresponds to 104.7% of free bromelain activity, confirming its integrity upon encapsulation. However, C-B-NP were unstable when stored in aqueous suspension, leading to freeze-drying studies of the formulation. Glycine and maltose were used as potential lyoprotectors and the formulation optimized by a factorial design; resultant products presented short resuspension time, slightly altered nanoparticles mean size and increased encapsulation rate compared to the previous liquid form. Maltose was able to better maintain formulation's enzymatic activity over time (90 days), especially when stored under refrigeration. Therefore, freeze-dried C-B-NP can effectively improve bromelain and nanoparticle stability, which allow further in vivo applications as a dried powder for topical administration or as a raw material for other dosage forms.

Sunscreens contain molecules with the ability to absorb and/or reflect UVA (ultraviolet A) and UVB (ultraviolet B) radiation, thereby preventing this radiation from reaching the epidermis or dermis. Their photo stabilities after exposure to UV radiation are well known and described, but there is little data on the stability of these filters after fluorescent indoors light radiation, such as from light emitted by commercial lamps present in homes and offices. Those lamps can expose people to varying levels of UVB, UVA, visible light, and IR (infrared). This study assesses the photostability of four different commercial products containing chemical sun filters after artificial UV and fluorescent irradiation, correlating the UVB and UVA absorption efficiencies of each product against the different types of radiation. The tested products were applied on a plate of polymethylmethacrylate (PMMA) and irradiated by a solar simulator with specific filters for UVA and UVB and a commercial fluorescent light source. According to the results, three formulations did not show photostability, suffering significant changes in their UV absorption spectra, and one of the selected formulations can be considered photostable. This reinforces the importance of conducting stability studies for sunscreen formulations in different conditions, including under artificial (indoor) light exposure.

Permeation of sunscreens agents reduces its effectiveness and safety, leading to systemic circulation and causing unknown adverse effects. In order to maintain the sunscreen efficacy and safety, the filters must stay on the skin surface, with minimum penetration through dermis. Even facing the possibility of filters permeation, the use of sunscreen is important to avoid skin damage as erythema, free-radicals formation, skin ageing and skin cancer, caused by ultraviolet radiation. Aiming potential side effects caused by topical absorption of sunscreens, studies are carried to improve formulation characteristics and stability, reduce skin permeation and evaluate sun protections factor (SPF). Current assays to detect the permeation of sunscreens involve in vivo or in vitro studies, to simulate physiological conditions of use. The aim of this review is to revisit sunscreen skin permeation data over the last decade and the factors that can enhance skin permeation or improve the sunscreen efficacy.

Layered double hydroxides (LDHs), which are two-dimensionally organized structures, are known as anionic clays. LDHs present great properties such as excellent biocompatibility and stability. Besides that, it can harbor several molecules in their interlayer region. The benefits of this technology applied to photoprotective molecules, are presented and discussed. LDHs, when applied to sunscreens, can protect the skin against UVA and UVB radiation. On the other hand, application of some photoprotective molecules has limited use due to reported cases of toxicity and skin irritation. The structure of LDHs have the ability of absorbing ultraviolet rays and promotes a photoprotective effect on its own. Also, they act as stabilizers of photoprotective molecules and prevent direct contact of these molecules with the skin.

Objectives The objectives of this study were to analyze adverse drug events (ADEs) related to admissions to a pediatric emergency unit and to identify the associated risk factors. Methods This was a prospective study. Demographic data and details of medications were collected for each patient admitted. Case studies were performed by clinical pharmacists and the clinical team to discuss whether the admission was due to an ADE and to characterize the ADE. Multivariate logistic regression was used for statistical analysis. Results In total, 1708 pediatric patients were included in this study. Adverse drug events were the cause of hospital admission in 12.3% of the studied population. The majority of patients presenting with an ADE were in the age group of 0 to 5 years (61.6%), had a mean ± SD age of 4.9 ± 3.9 years, were female (51.2%), were Caucasian (72.0%), and had infectious disorders (49.3%). High frequencies of medication errors (68.8%), use of drugs to treat respiratory disorders (27.7%), and ADEs of mild severity (75.3%) were reported. The risk of being admitted to the pediatric emergency unit for any ADE increased in cases of neurological (odds ratio [OR], 4.63; 95% confidence interval [CI], 2.38-8.99), dermatological (OR, 3.16; 95% CI, 1.93-5.18), and respiratory (OR, 3.02; 95% CI, 1.89-4.83) disorders. Conclusions A high frequency of ADE-related admissions to the pediatric emergency unit was observed. The risk of being admitted to the pediatric emergency unit for any ADE increased in cases of neurological, dermatological, and respiratory disorders. Clinical pharmacists play an important role in the identification of ADEs and the education of child caregivers and health care providers concerning pediatric medication.

Summary Ovarian clear cell and endometrioid carcinomas (type I) are thought to develop from endometriosis. ARID1A loss of expression is known to be related to the promotion of the endometriosis carcinogenesis. Despite the diverse origins and prognosis of type I and type II carcinomas, surgery followed by platinum-based chemotherapy is the mainstay of treatment for both. Limited knowledge about the expression of targeted therapies' biomarkers prevents the use of such markers as potential guides for tailored treatment. This study aimed to evaluate the expression of ARID1A gene and target therapies biomarkers (VEGF, PD-L1, and PARP-1) in ovarian clear cell and endometrioid carcinomas and endometriosis, and its relationship with prognosis. Forty-six ovarian clear cell and endometrioid carcinomas, and 24 endometriosis foci samples retrieved from the same surgical specimens were studied. ARID1A, VEGF, PD-L1, and PARP-1 immunohistochemistry expression was compared in carcinomas and endometriosis with regard to the clinicopathological features and prognosis. We found that endometriosis was associated with increased rates of diagnosis of cancer in the initial stages (P = .008). Different levels of expression of all biomarkers were detected in clear cell and endometrioid carcinomas and endometriosis. However, only the VEGF expression level showed a significant increase in the carcinoma group when compared with endometriosis (P = .0002). PARP-1 overexpression correlated with worse progression-free survival (P = .03) and overall survival (P = .01). In conclusion, endometriosis and ovarian clear cell and endometrioid carcinomas exhibited ARID1A loss of expression, and VEGF, PD-L1, and PARP-1 expression. PARP-1 overexpression in clear cell and endometrioid carcinomas was associated with early recurrence and worse overall survival.

Background Berries are known for their antioxidant activity due to the presence of flavonoids. Antioxidants' usage guarantees skin protection against free radicals and, flavonoids, especially, can act as sunscreen. The aim of this paper was to evaluate solar protection factor (SPF) and antioxidant activity in vitro of blackberry and raspberry extracts incorporated in topical formulation and study their stability. Results Raspberry presented 29.93 mg of anthocyanins/100 g of fruit and blackberry 65.58 mg of anthocyanins/100 g of fruit. In vitro solar protection factor was 54.57 to blackberry and 37.32 to raspberry. When incorporated in O/W emulsions, final formulations showed light pink color, creamy aspect, and typical fruity odor. Formulations submitted to indirect light and stove showed odor and color alterations. Conclusions Based on the results, formulations containing extracts should be kept under refrigeration in opaque package to ensure stability due to the presence of flavonoids. In addition, blackberry and raspberry extracts are potential natural alternatives to be used as sunscreen and to prevent skin aging.

Background Cisplatin is a high-potency anticancer agent; however, it causes significant adverse drug reactions (ADRs). Potential pharmacokinetic markers must be studied to predict or prevent cisplatin-induced ADRs and achieve better prognosis. This study was designed to investigate the relationship between ADRs and kinetics of cisplatin excretion in the urine of patients undergoing high-dose cisplatin chemotherapy and radiotherapy for head and neck cancer. Methods Outpatients with head and neck cancer received a first cycle of high-dose cisplatin chemotherapy (80–100 mg/m2) concurrent to radiotherapy. ADRs (haematological, renal, and gastrointestinal reactions) were classified based on severity by National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE, version 4, grade 0–4). The kinetics of cisplatin excretion in urine was evaluated by high-performance liquid chromatography over three time periods: 0–12, 12–24, and 24–48 h after the administration of cisplatin. Spearman Correlation test and regression analysis were performed to assess the relationship between ADRs and cisplatin excretion in the urine. Results In total, 59 patients with a mean age of 55.6 ± 9.4 years were analysed; most patients were male (86.4%), white (79.7%), and with pharyngeal tumours in advanced stages (66.1%). The most frequently observed ADRs were anaemia (81.4%), lymphopenia (78%), and nausea (64.4%); mostly grades 1 and 2 of toxicity. The mean cisplatin excretion was 70.3 ± 64.4, 7.3 ± 6.3, and 5 ± 4 μg/mg creatinine at 0–12, 12–24, and 24–48 h, respectively. Statistical analysis showed that the amount of cisplatin excreted did not influence the severity of ADRs. Conclusions The most frequent ADRs were anaemia, lymphopenia, and nausea. Grades 1 and 2 were the severities for most ADRs. The period over which the highest cisplatin excretion observed was 0–12 h after chemotherapy, and cisplatin excretion could not predict toxicity. Graphical abstract

Patients in intensive care unit are prescribed large numbers of drugs, highlighting the need to study potential Drug-Drug Interactions in this environment. The aim of this study was to delineate the prevalence and risk of potential drug-drug interactions between medications administered to patients in an ICU. This cross-sectional observational study was conducted during 12 months, in an adult ICU of a teaching hospital. Inclusion criteria were: prescriptions with 2 or more drugs of patients admitted to the ICU for > 24 hours and age of ≥18 years. Potential Drug-Drug Interactions were quantified and classified through MicromedexTM database. The 369 prescriptions included in this study had 205 different drugs, with an average of 13.04 ± 4.26 (mean ± standard deviation) drugs per prescription. Potential Drug-Drug Interactions were identified in 89% of these, with an average of 5.00 ± 5.06 interactions per prescription. Of the 405 different pairs of potentially interacting drugs identified, moderate and major interactions were present in 74% and 67% of prescriptions, respectively. The most prevalent interaction was between dipyrone and enoxaparin (35.8%), though its clinical occurrence was not observed in this study. The number of potential Drug-Drug Interactions showed significant positive correlations with the length of stay in the intensive care unit, and with the number of prescribed drugs. Acknowledging the high potential for Drug-Drug Interactions in the ICU represents an important step toward improving patient safety and best therapy results.

There is a lack of safety data supporting the use of hormone therapy in women who have had breast cancer and who have complained of genitourinary syndrome of menopause (GSM). The objective was to test the efficacy of two non-hormonal therapies for vaginal dryness.This was a randomized trial with 52 women with breast cancer who were being treated with tamoxifen and who complained of vaginal dryness. The volunteers answered two questionnaires to evaluate sexual function (Female Sexual Function Index, FSFI) and a customized GSM questionnaire. The women were randomized into two groups: 25 (48.1%) in the polyacrylic acid group and 27 (51.9%) in the lubricant group, using either one of the treatments for 30 days, and after they were invited to answer the questionnaires again.There was improvement in the FSFI after both treatments. The polyacrylic acid group showed a decrease in sexual dysfunction from 96% to 24% (p 0.0001) and the lubricant group showed a decrease from 88.9% to 55.6% (p = 0.0027).The results of this study showed that both treatments improved sexual function; however, polyacrylic acid was superior to the lubricant in treating sexual dysfunction.

Biotechnology processes are the unique feasible way for the production of some pharmaceutical active principles. Thus, developments in molecular biology, recombinant techniques, separation, and purification methods have a primordial role because of the innovative characteristic and economic impact in obtaining these new drugs through biotechnological approaches. This special issue compiles a series of relevant studies on different biotechnological fields and applications, reporting up-to-date developments on downstream and upstream biopharmaceuticals.

Oncologic inpatients often require multiple drug therapy. They may be at higher risk of experiencing prescribing errors, which pharmacist interventions may help to avoid. This study aimed to evaluate the types of prescribing errors, pharmaceutical interventions and differences in clinical significance, in prescriptions for hospitalised patients with breast and gynaecological cancer. A cross-sectional, prospective study was conducted at the oncology ward of a clinic specialised in breast and gynaecology cancer. A clinical pharmacist analysed prescriptions, identified errors, performed interventions and classified clinical significance. A total of 1,874 prescriptions of 248 patients were evaluated; 11.5% prescriptions were involved at least in one prescribing error, totalising 283 errors. The most common error was unsafe medication due to drug interaction (89[31.4%]). Drugs for the alimentary tract and metabolism, and nervous system were the most involved in errors with statistical association (p = .0246 and p = .0002 respectively). Of the 294 interventions, 73.5% were accepted. The clinical significance of prescribing errors and interventions were classified as significant and very significant respectively. The pharmacist interventions obtained a good acceptance rate and impact significantly, avoiding prescribing errors classified as significant.

Background: Highly active antiretroviral therapy (HAART) is complex and many factors contribute to a patient’s response to initial therapy including adherence, drug effectiveness, and tolerance. Close HAART follow-up is needed, particularly when there are concurrent therapies such as prophylactic antibiotics and medications for the treatment of comorbidities. Objective: To assess the effectiveness of pharmacist intervention in reducing drug related problems in HIV/AIDS outpatients (intervention group) and in improving clinical parameters in the intervention group compared to the control group. Methods: We conducted a prospective controlled intervention study with patients paired by gender and initial T CD4+ lymphocyte (CD4) count. HIV-infected patients of a public outpatient service were enrolled for the study by consecutive and convenience sampling. Patients selected for the study were divided into a control group and an intervention group. Both groups were followed for one year; however, only the intervention group received pharmaceutical care. The primary outcome was the drug related problem (DRP) analysis for the intervention group. Secondary outcomes were CD4 count and viral load evaluation for both groups. Results: There was a total of 143 patients enrolled in this study, with 53 (37.06%) patients in the control group and 90 (62.94%) patients in the intervention group. A total of 202 pharmacist interventions with 193 pharmacist-patient and 9 pharmacist-physician interventions were proposed. After one year of pharmaceutical care, a reduction of 38.43% between the initial and final DRP was found (p=0.0001). The most common DRPs found were related to medication safety. The intervention group showed a mean increase of 84% for the CD4 count in comparison with that observed in the control group. The viral load was not significantly different between the final and initial mean values for both groups. Conclusion: Pharmacist appointments enabled identification, prevention, and solving of drug related problems, especially those related to drug safety. Also, pharmacist interventions improved adherence and increased HAART effectiveness as suggested by the higher elevation in the CD4 count seen in the intervention group in comparison with the control group.