Citotoxicidade de curcumina presente em nanoparticulas de quitosana/sultato de condroitina contendo lecitina

Dissertação (mestrado)–Universidade de Brasília, Universidade UnB de Planaltina, Programa de Pós-Graduação em Ciência de Materiais, 2015.

Valorização integrada de resíduos e subprodutos da extração do azeite: extração e caraterização de compostos bioativos do bagaço de azeitona

Dissertação de Mestrado, Tecnologia de Alimentos, Instituto Superior de Engenharia, Universidade do Algarve, 2016

Methotrexate nanoparticle delivery system for treatment of inflammatory bowel disease in pediatric patients

Purpose: To evaluate the efficacy and safety of methotrexate (MTX) nanoparticles in pediatric patients with inflammatory bowel disease (IBD). Methods: In this randomized, open-label clinical study, 28 pediatric patients with moderate to severe IBD were randomly assigned to treatment (MTX nanoparticles,15 mg/week) or control (azathioprine, AZA, 2 mg/kg/day) group. Nanoparticles were synthesized by adding calcium chloride to sodium alginate solution containing MTX, and was further treated with poly-L-lysine aqueous solution. The nanoparticles were evaluated for particle size, zeta potential and drug encapsulation efficacy. Erythrocyte sedimentation rate, C-reactive protein, aspartate aminotransferase, alanine transaminase, and disease activity scores were used to assess IBD remission. Results: Nanoparticle size, zeta potential and encapsulation efficacy were 164.4 ± 6.9 nm, -32.6 ± 3.7 mV, and 97.8 ± 4.2 %, respectively. After 12 weeks of therapy, the mean Pediatric Crohn\'s Disease Activity Index (PCDAI) scores for control and treatment groups were 22.3 ± 2.14 and 16.8 ± 1.87, respectively, while mean Pediatric Ulcerative Colitis Activity (PUCAI) Index scores were 24.3 ± 1.47 and 18.7 ± 1.92, respectively. Eight patients in the treatment and five patients in the control group achieved remission. Biochemical parameters varied significantly between the groups. Conclusion: MTX nanoparticles are safe and more effective than standard first-line IBD therapy. However, further studies are required to determine the suitability of the formulation for therapeutic use.

Síntese e caracterização de nanocompósitos magnéticos empregando polimerização radicalar em meios homogêneo (blk) e heterogêneo (miniemulsão)

Tese (doutorado)—Universidade de Brasília, Instituto de Química, Curso de Pós-Graduação em Química, 2016.

Manufacturing techniques and surface engineering of polymer based nanoparticles for targeted drug delivery to cancer

The evolution of polymer based nanoparticles as a drug delivery carrier via pharmaceutical nano/microencapsulation has greatly promoted the development of nano- and micro-medicine in the past few decades. Poly(lactide-co-glycolide) (PLGA) and chitosan, which are biodegradable and biocompatible polymers, have been approved by both the Food & Drug Administration (FDA) and European Medicine Agency (EMA), making them ideal biomaterials that can be advanced from laboratory development to clinical oral and parental administrations. PLGA and chitosan encapsulated nanoparticles (NPs) have successfully been developed as new oral drug delivery systems with demonstrated high efficacy. This review aims to provide a comprehensive overview of the fabrication of PLGA and chitosan particulate systems using nano/microencapsulation methods, the current progress and the future outlooks of the nanoparticulate drug delivery systems. Especially, we focus on the formulations and nano/micro-encapsulation techniques using top-down techniques. It also addresses how the different phases including the organic and aqueous ones in the emulsion system interact with each other and subsequently influence the properties of the drug delivery system. Besides, surface modification strategies which can effectively engineer intrinsic physicochemical properties are summarised. Finally, future perspectives and potential directions of PLGA and chitosan nano/microencapsulated drug systems are outlined.

Antiparasitic and immunomodulatory potential of oral nanocapsules encapsulated lactoferrin protein against plasmodium berghei

AIM: To analyze the effect of native buffalo lactoferrin (buLf) protein along with its nanoformulation using alginate-enclosed, chitosan-conjugated, calcium phosphate buffalo Lf nanocapsules (AEC-CCo-CP-buLf NCs) against rodent parasite Plasmodium berghei. MATERIALS & METHODS: BALB/c mice were infected with malaria parasite and efficacy of the proteins (buLf and NCs) was evaluated by measuring parasitemia, initialization, role of miRNA in absorption of NCs, parasite load by histopathology and quantitative determination, cytokine levels, bioavailability and immunohistochemistry to localize Lf protein. RESULTS: NCs significantly reduced the parasite load in mice compared with buLf and untreated group. NCs were found to be modulating the disease profile of mice as shown by immunohistochemistry, free radical ion production and higher survival tendency. CONCLUSION: Our study confirms that NCs internalized and changed the expression of miRNAs that further enhanced their uptake in various organs leading to inhibitory effect against the parasite as well as maintenance of the Fe metabolism.

Development of drug-loaded chitosan-vanillin nanoparticles and its cytotoxicity against HT-29 cells

Chitosan as a natural polysaccharide derived from chitin of arthropods like shrimp and crab, attracts much interest due to its inherent properties, especially for application in biomedical materials. Presently, biodegradable and biocompatible chitosan nanoparticles are attractive for drug delivery. However, some physicochemical characteristics of chitosan nanoparticles still need to be further improved in practice. In this work, chitosan nanoparticles were produced by crosslinking chitosan with 3-methoxy-4-hydroxybenzaldehyde (vanillin) through a Schiff reaction. Chitosan nanoparticles were 200-250 nm in diameter with smooth surface and were negatively charged with a zeta potential of - 17.4 mV in neutral solution. Efficient drug loading and drug encapsulation were achieved using 5-fluorouracil as a model of hydrophilic drug. Drug release from the nanoparticles was constant and controllable. The in vitro cytotoxicity against HT-29 cells and cellular uptake of the chitosan nanoparticles were evaluated by methyl thiazolyl tetrazolium method, confocal laser scanning microscope and flow cytometer, respectively. The results indicate that the chitosan nanoparticles crosslinked with vanillin are a promising vehicle for the delivery of anticancer drugs.

Nano-precipitation : preparation and application in the field of pharmacy

Over the last 30 years, nanoparticle-based medicine has received tremendous attention due to its advances with smart therapeutics and less toxicity. Few nanomedicine products have been approved for commercial use in the clinic (such as Doxil®, Ambraxane®…). Nanomedicine research is still at its early stage and the preparation of nanoparticles must be carefully considered. Systems involving further increased supersaturation, either via solvent evaporation, temperature reduction or anti-solvent mixture, were suggested to be capable of inducing nanoprecipitation (NPT). Since this technique is straight-forward, fast and easy to duplicate in practice, it is highly preferred and recommended. In this review, the process of NTP was described and discussed in detail. Factors that affect the encapsulation efficiency, the nanoparticle size, the morphology and the stability of nanoparticles prepared by NTP were described. This process is one of the most preferable processes for preparing solid nano-protein due to their elegant techniques that preserve the bioactivity of proteins. Although the production of nanoparticles by this process has not been applied in the pharmaceutical industry due to the organic solvent issue, the production equipment for large-scale has been marketed.

Microchannel emulsification study on formulation and stability characterization of monodisperse oil-in-water emulsions encapsulating quercetin

The study used microchannel emulsification (MCE) to encapsulate quercetin in food grade oil-in-water (O/W) emulsions. A silicon microchannel plate (Model WMS 1-2) comprised of 10,300 discrete 10 × 104 μm microslots was connected to a circular microhole with an inner diameter of 10 μm. 1% (w/w) Tween 20 was used as optimized emulsifier in Milli-Q water, while 0.4 mg ml-1 quercetin in different oils served as a dispersed phase. The MCE was carried by injecting the dispersed phase at 2 ml h-1. Successful emulsification was conducted below the critical dispersed phase flux, with a Sauter mean diameter of 29 μm and relative span factor below 0.25. The O/W emulsions remained stable in terms of droplet coalescence at 4 and 25 °C for 30 days. The encapsulation efficiency of quercetin in the O/W emulsions was 80% at 4 °C and 70% at 25 °C during the evaluated storage period.

Monodisperse aqueous microspheres encapsulating high concentration of l-ascorbic acid: insights of preparation and stability evaluation from straight-through microchannel emulsification

Stabilization of l-ascorbic acid (⌊-AA) is a challenging task for food and pharmaceutical industries. The study was conducted to prepare monodisperse aqueous microspheres containing enhanced concentrations of ⌊-AA by using microchannel emulsification (MCE). The asymmetric straight-through microchannel (MC) array used here constitutes 11 × 104 μm microslots connected to a 10 μm circular microholes. 5-30% (w/w) ⌊-AA was added to a Milli-Q water solution containing 2% (w/w) sodium alginate and 1% (w/w) magnesium sulfate, while the continuous phase constitutes 5% (w/w) tetraglycerol condensed ricinoleate in water-saturated decane. Monodisperse aqueous microspheres with average diameters (dav) of 18.7-20.7 μm and coefficients of variation (CVs) below 6% were successfully prepared via MCE regardless of the ⌊-AA concentrations applied. The collected microspheres were physically stable in terms of their dav and CV for >10 days of storage at 40°C. The aqueous microspheres exhibited ⌊-AA encapsulation efficiency exceeding 70% during the storage.

Formulation of monodisperse oil-in-water emulsions loaded with ergocalciferol and cholecalciferol by microchannel emulsification: Insights of production characteristics and stability

Nutritional deficiencies of ergocalciferol (VD2) and cholecalciferol (VD3) cause skeletal deformations. The primary aim of this study was to encapsulate VD2 and VD3 in food-grade oil-in-water (O/W) emulsions by using microchannel emulsification (MCE). Silicon asymmetric straight-through microchannel (MC) array consisting of 10 313 channels, each having an 11 × 104 μm microslot connected to a 10 μm circular microholes. 1% (w/w) sodium cholate or Tween 20 in water was used as the continuous phase, while 0.5% (w/w) of each VD2 and VD3 in different oils served as the dispersed phase. Monodisperse O/W emulsions with Sauter mean diameters of 28 to 32 μm and relative span factor widths below 0.3 were formulated via an asymmetric straight-through MC array under appropriate operating conditions. The monodisperse O/W emulsions stabilised with Tween 20 remained stable for >30 days with encapsulation efficiencies (EEs) of VD2 and VD3 of above 70% at 4 and 25 °C. In contrast, those stabilised with sodium cholate had stability of >30 days with their EEs of over 70% only at 25 °C.

Formulation of monodisperse water-in-oil emulsions encapsulating calcium ascorbate and ascorbic acid 2-glucoside by microchannel emulsification

The aim of this study was to investigate the effects of the emulsifying conditions and emulsifier type on production of water-in-oil (W/O) emulsions encapsulating ascorbic acid derivatives by microchannel (MC) emulsification. The ascorbic acid derivatives added in a dispersed aqueous phase are calcium ascorbate (AA-Ca) and ascorbic acid 2-glucoside (AA-2G). The continuous phase used was decane, soybean oil or their mixture, containing 5% (w/w) tetraglycerin monolaurate condensed ricinoleic acid ester or sorbitan trioleate. A hydrophobized silicon MC array plate (model: MS407) with a channel depth of 7μm was used for MC emulsification. The use of MC emulsification enabled successful encapsulation of AA-Ca and AA-2G in monodisperse W/O emulsion droplets with coefficients of variation (CV) less than 7%. Their average droplet diameter (dav) increased with increasing the continuous-phase viscosity that is similar or higher than the dispersed-phase viscosity. The dav and CV of the resultant monodisperse W/O emulsions were unaffected by the dispersed-phase flow rate below critical values of 1.2-1.6mLh-1 when using decane as the continuous-phase medium.

Des aptamères pour améliorer l’encapsulation et la libération contrôlée des liposomes

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Geospatial Data Indexing Analysis and Visualization via Web Services with Autonomic Resource Management

With the exponential growth of the usage of web-based map services, the web GIS application has become more and more popular. Spatial data index, search, analysis, visualization and the resource management of such services are becoming increasingly important to deliver user-desired Quality of Service. First, spatial indexing is typically time-consuming and is not available to end-users. To address this, we introduce TerraFly sksOpen, an open-sourced an Online Indexing and Querying System for Big Geospatial Data. Integrated with the TerraFly Geospatial database [1-9], sksOpen is an efficient indexing and query engine for processing Top-k Spatial Boolean Queries. Further, we provide ergonomic visualization of query results on interactive maps to facilitate the user’s data analysis. Second, due to the highly complex and dynamic nature of GIS systems, it is quite challenging for the end users to quickly understand and analyze the spatial data, and to efficiently share their own data and analysis results with others. Built on the TerraFly Geo spatial database, TerraFly GeoCloud is an extra layer running upon the TerraFly map and can efficiently support many different visualization functions and spatial data analysis models. Furthermore, users can create unique URLs to visualize and share the analysis results. TerraFly GeoCloud also enables the MapQL technology to customize map visualization using SQL-like statements [10]. Third, map systems often serve dynamic web workloads and involve multiple CPU and I/O intensive tiers, which make it challenging to meet the response time targets of map requests while using the resources efficiently. Virtualization facilitates the deployment of web map services and improves their resource utilization through encapsulation and consolidation. Autonomic resource management allows resources to be automatically provisioned to a map service and its internal tiers on demand. v-TerraFly are techniques to predict the demand of map workloads online and optimize resource allocations, considering both response time and data freshness as the QoS target. The proposed v-TerraFly system is prototyped on TerraFly, a production web map service, and evaluated using real TerraFly workloads. The results show that v-TerraFly can accurately predict the workload demands: 18.91% more accurate; and efficiently allocate resources to meet the QoS target: improves the QoS by 26.19% and saves resource usages by 20.83% compared to traditional peak load-based resource allocation.

Des aptamères pour améliorer l’encapsulation et la libération contrôlée des liposomes

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