Functional hybrid nanoemulsions for sumatriptan intranasal delivery

In recent years, advanced nanohybrid materials processed as pharmaceuticals have proved to be very advantageous. Triptans, such as the commercially available intranasal sumatriptan (SMT), are drugs employed in the treatment of painful migraine symptoms. However, SMT effectiveness by the intranasal route is limited by its high hydrophilicity and poor mucoadhesion. Therefore, we designed hybrid nanoemulsions (NE) composed of copaiba oil as the organic component plus biopolymers (xanthan, pectin, alginate) solubilized in the continuous aqueous phase, aiming at the intranasal release of SMT (2% w/v). Firstly, drug-biopolymer complexes were optimized in order to decrease the hydrophilicity of SMT. The resultant complexes were further encapsulated in copaiba oil-based nanoparticles, forming NE formulations. Characterization by FTIR-ATR, DSC, and TEM techniques exposed details of the molecular arrangement of the hybrid systems. Long-term stability of the hybrid NE at 25°C was confirmed over a year, regarding size (~ 120 nm), polydispersity (~ 0.2), zeta potential (~ −25 mV), and nanoparticle concentration (~ 2.1014 particles/mL). SMT encapsulation efficiency in the formulations ranged between 41–69%, extending the in vitro release time of SMT from 5 h (free drug) to more than 24 h. The alginate-based NE was selected as the most desirable system and its in vivo nanotoxicity was evaluated in a zebrafish model. Hybrid NE treatment did not affect spontaneous movement or induce morphological changes in zebrafish larvae, and there was no evidence of mortality or cardiotoxicity after 48 h of treatment. With these results, we propose alginate-based nanoemulsions as a potential treatment for migraine pain.Fil: Ribeiro, Lígia N. M.. Universidade Estadual de Campinas; BrasilFil: Rodrigues da Silva, Gustavo H.. Universidade Estadual de Campinas; BrasilFil: Couto, Verônica M.. Universidade Estadual de Campinas; BrasilFil: Castro, Simone R.. Universidade Estadual de Campinas; BrasilFil: Breitkreitz, Márcia C.. Universidade Estadual de Campinas; BrasilFil: Martinez, Carolina Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; Argentina. Universidad Nacional de Quilmes; ArgentinaFil: Igartúa, Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes; ArgentinaFil: Prieto, Maria Jimena. Universidad Nacional de Quilmes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; ArgentinaFil: de Paula, Eneida. Universidade Estadual de Campinas; Brasi

Uncovering the Cyanobacterial Chemical Diversity: The Search for Novel Anticancer Compounds

This article belongs to the Proceedings of The 7th Iberian Congress on Cyanotoxins/3rd Iberoamerican Congress on Cyanotoxins[Abstract] Cancer has a tremendous negative socio-economic impact on our society. Thus, the discovery of new and more effective anticancer drugs is of utmost importance. To address this societal challenge, the main goal of the CYANCAN project was the discovery of anticancer compounds from cyanobacteria. These photosynthetic bacteria are considered among the most promising groups capable of producing metabolites with pharmaceutical applications. A valuable and underexplored natural resource that can underpin the discovery of promising compounds can be found in the Blue Biotechnology and Ecotoxicology Culture Collection (LEGE-CC) at CIIMAR (Interdisciplinary Centre of Marine and Environmental Research), comprising more than 700 different cyanobacterial strains. Herein, we present the recent advances implemented for finding robust anticancer lead compounds from LEGE-CC cyanobacteria. For this purpose, we developed a natural product library. Sixty cyanobacterial strains, representative of LEGE-CC biodiversity, were chromatographed to yield 480 fractions that were tested for their cytotoxic activity against 2D and 3D models of human colon carcinoma (HCT 116). The conjugation of monolayer assays and 3D cancer spheroids led to the selection of 11 active fractions, of which the chemical space was studied using an untargeted metabolomics approach. The putative annotation and identification of several compounds led to the selection of two marine strains for compound isolation: Leptothoe sp. and Lusitaniella coriacea. The isolation of the compounds was guided through bioactivity assays and mass spectrometry. These molecules were purified from the crudes by employing several chromatography methods, and the chemical structures were determined by means of NMR (nuclear magnetic resonance) and MS/MS (tandem mass spectrometry) experiments. Thus, a novel macrolide-type compound was isolated from Leptothoe sp., which presented a highly cytotoxic activity against our cancer cell models. Its effects on cancer vascularization and metastasis were studied using the zebrafish model. Moreover, from L. coriacea, five unprecedented salicyl-capped thiazol(in)e NRPs-PKs (nonribosomal peptides-polyketides) compounds were isolated. These compounds showed the potential to act as reversers of P-glycoprotein efflux activity.CIIMAR strategic funds UIDB/04423/2020 and UIDP/04423/2020; CYANCAN PTDC/MED-QUI/30944/2017, co-financed by NORTE 2020, Portugal 2020, and the European Union through the ERDF. EMERTOX: EU Horizon 2020 R&I programme under the Marie Skłodowska-Curie grant agreement No 778,069. Ribeiro, T: FCT grant SFRH/BD/139131/2018. Castelo-Branco, R: FCT grant SFRH/BD/136367/2018Centro Interdisciplinar de Investigação Marinha e Ambiental (Porto); UIDB/04423/2020Portugal. Fundação para a Ciência e a Tecnologia; PTDC/MED-QUI/30944/2017Portugal. Fundação para a Ciência e a Tecnologia; SFRH/BD/139131/2018Portugal. Fundação para a Ciência e a Tecnologia; SFRH/BD/136367/201

Elderly widows' experience of sexuality and their perceptions regarding the family's opinion

O objetivo deste trabalho foi descrever a vivência da sexualidade por mulheres idosas viúvas, frequentadoras de um Centro de Convivência do Idoso, e verificar a percepção quanto à opinião dos seus familiares. Tratou-se de uma pesquisa qualitativa e exploratório-descritiva. Os dados foram coletados por meio de entrevistas semiestruturadas e submetidos à análise de conteúdo temática. Emergiram desta as categorias: 1) a vivência da sexualidade sofreu algumas modificações após o estado de viuvez garantindo submissão às normas e regras sociais para o comportamento feminino; 2) as idosas assumem ter optado pela vida sem um novo companheiro; 3) a família apoia o convívio social, mas não existe declaração de apoio para novos relacionamentos amorosos; e 4) houve ressignificação das questões de gênero no tocante às mudanças relativas ao papel social da mulher, depois da viuvez. Concluímos, portanto, que essas mulheres não vivem, de forma plena e livre, sua sexualidade, pois se submetem às normas sociais.The aim of this study was to describe the experience of sexuality of elderly widows attending an Elderly Community Centre and to verify their perceptions regarding their relatives' opinion. This was a qualitative and descriptive-exploratory research. Data were collected through semi-structured interviews and submitted to a thematic content analysis. The following categories emerged: 1) the experience of sexuality was modified after the women became widows, so that the female behavior complies with social norms and rules; 2) the elderly widows assume they have opted for life without a new partner; 3) the family supports social interaction, but there is no statement of support for new loving relationships; and 4) gender issues were redefined in relation to changes in the social role of women after widowhood. We conclude, therefore, that these women do not experience, neither fully nor freely, their sexuality, because they submit to the social norms

Bionanocomposites quitosano-hidróxido doble laminar recubiertos con pectina como sistemas para la liberación controlada de fármacos de acción en el colon

Comunicación oral dada en la XXIII Reunión de la Sociedad Española de Arcillas que tuvo lugar en Toledo (España) del 10 al 12 de septiembre de 2014.Proyectos MAT2012-31759 (CICYT, España) y MP1202 (COST Action, UE)

Alginate/magnetic graphite bionanocomposites for drug delivery applications

Oral presentation given at the Scientific Workshop "Biomedical, Health and Bio-related Applications of Hybrid Materials", held in Barcelona (Spain) on June 8-9th, 2015.Bionanocomposites based on the assembly of biopolymers and inorganic solids offer interesting properties for application in biomedicine as drug delivery systems (DDS),1 especially those based on layered double hydroxides (LDH) that can incorporate a large variety of anionic drugs and be further coated with a protective polymeric matrix to reach a better control of the drug release.2,3 In this study, new magnetic bio-hybrid matrices are developed from the assembly of the polysaccharide alginate and magnetic graphite nanoparticles, incorporating ibuprofen (IBU) intercalated in Mg¿Al LDH as third component.4 The resulting magnetic bionanocomposite DDS was processed as beads or films, and evaluated in in vitro release tests with the aim to elucidate the role of interface interactions between the polysaccharide and both the magnetic graphite and the inorganic brucite-like layers. The magnetic graphite nanoparticles provide a protective effect against water uptake, improving the mechanical properties and slowing down the release rate of the drug. In addition, when ibuprofen was incorporated as the LDH¿IBU intercalation compound, the LDH host solid constitutes an extra physical barrier that improves the control on the release rate of the entrapped drug. These bionanocomposite systems could be also stimulated by means of an external magnetic field enhancing the release rate of ibuprofen, which would allow to modulate the dose of released drug when required

Bionanocomposites containing magnetic graphite as potential systems for drug delivery

New magnetic bio-hybrid matrices for potential application in drug delivery are developed from the assembly of the biopolymer alginate and magnetic graphite nanoparticles. Ibuprofen (IBU) intercalated in a Mg-Al layered double hydroxide (LDH) was chosen as a model drug delivery system (DDS) to be incorporated as third component of the magnetic bionanocomposite DDS. For comparative purposes DDS based on the incorporation of pure IBU in the magnetic bio-hybrid matrices were also studied. All the resulting magnetic bionanocomposites were processed as beads and films and characterized by different techniques with the aim to elucidate the role of the magnetic graphite on the systems, as well as that of the inorganic brucite-like layers in the drug-loaded LDH. In this way, the influence of both inorganic components on the mechanical properties, the water uptake ability, and the kinetics of the drug release from these magnetic systems were determined. In addition, the possibility of modulating the levels of IBU release by stimulating the bionanocomposites with an external magnetic field was also evaluated in in vitro assays.This work was supported by the CICYT, Spain (project MAT2012-31759) and the EU COST Action MP1202. L.N.M.R. acknowledges the CAPES (Brazil) for her fellowship. FMAM acknowledges Brazilian agencies FAPESP, CAPES and CNPq for financial support

Articaine in functional NLC show improved anesthesia and anti-inflammatory activity in zebrafish

Anesthetic failure is common in dental inflammation processes, even when modern agents, such as articaine, are used. Nanostructured lipid carriers (NLC) are systems with the potential to improve anesthetic efficacy, in which active excipients can provide desirable properties, such as anti-inflammatory. Coupling factorial design (FD) for in vitro formulation development with in vivo zebrafish tests, six different NLC formulations, composed of synthetic (cetyl palmitate/triglycerides) or natural (avocado butter/olive oil/copaiba oil) lipids were evaluated for loading articaine. The formulations selected by FD were physicochemically characterized, tested for shelf stability and in vitro release kinetics and had their in vivo effect (anti-inflammatory and anesthetic effect) screened in zebrafish. The optimized NLC formulation composed of avocado butter, copaiba oil, Tween 80 and 2% articaine showed adequate physicochemical properties (size = 217.7 ± 0.8 nm, PDI = 0.174 ± 0.004, zeta potential = − 40.2 ± 1.1 mV, %EE = 70.6 ± 1.8) and exhibited anti-inflammatory activity. The anesthetic effect on touch reaction and heart rate of zebrafish was improved to 100 and 60%, respectively, in comparison to free articaine. The combined FD/zebrafish approach was very effective to reveal the best articaine-in-NLC formulation, aiming the control of pain at inflamed tissues10CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP1171199; 2115145217/15174-5; 14/14457-

Mucoadhesive, Thermoreversible Hydrogel, Containing Tetracaine-Loaded Nanostructured Lipid Carriers for Topical, Intranasal Needle-Free Anesthesia

Recent advances have been reported for needle-free local anesthesia in maxillary teeth by administering a nasal spray of tetracaine (TTC) and oxymetazoline, without causing pain, fear, and stress. This work aimed to assess whether a TTC-loaded hybrid system could reduce cytotoxicity, promote sustained permeation, and increase the anesthetic efficacy of TTC for safe, effective, painless, and prolonged analgesia of the maxillary teeth in dental procedures. The hybrid system based on TTC (4%) encapsulated in nanostructured lipid carriers (NLC) and incorporated into a thermoreversible hydrogel of poloxamer 407 (TTCNLC-HG4%) displayed desirable rheological, mechanical, and mucoadhesive properties for topical application in the nasal cavity. Compared to control formulations, the use of TTCNLC-HG4% slowed in vitro permeation of the anesthetic across the nasal mucosa, maintained cytotoxicity against neuroblastoma cells, and provided a three-fold increase in analgesia duration, as observed using the tail-flick test in mice. The results obtained here open up perspectives for future clinical evaluation of the thermoreversible hybrid hydrogel, which contains TTC-loaded NLC, with the aim of creating an effective, topical, intranasal, needle-free anesthesia for use in dentistry