Spray-dried structured lipid carriers for the loading of Rosmarinus officinalis: new nutraceutical and food preservative

Rosemary, an aromatic herb with significant antioxidative activity, is frequently used as food preservative and a source of nutraceuticals. Its antioxidant effect is mainly related to the presence of phenolic compounds, molecules considerably unstable and prone to irreversible physicochemical changes when exposed to external agents. We here proposed the loading of rosemary into structured lipid systems to improve its physicochemical properties. Four formulations were prepared using the same amount of rosemary lyophilized extract. The lipid phase was composed of stearic acid and oleic acid, and the aqueous phase, a varying combination of drying carriers (whey protein concentrate or gum Arabic) and surfactant (Poloxamer 188). The formulations were sonicated, spray-dried, and the obtained powders were characterized regarding the density (0.18 g/mL to 0.26 g/mL), particle size distribution (7 µm and 52 µm), and water solubility (29% to 48%). The antioxidant activity was determined by applying ABTS+ radical-scavenging assay and the results expressed per gram of lyophilized extract (150.6 mol Trolox/g to 376.4 mol Trolox/g), with a significantly lower/higher result seen for formulations containing gum Arabic and a higher concentration of Poloxamer. The prepared systems may have potential applications as preservative in foodstuff and as nutraceutical.This research has been sponsored by CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior) through the financial support (88887.368385/2019-00) granted to I.B., by the São Paulo ResearchFoundation (FAPESP) through the financial support (Grant N. 2018/26069-0 and 2011/10333-1) granted to W.P.O.and by the Portuguese Science and Technology Foundation (FCT) through the projects M-ERA-NET/0004/2015 (PAIRED) and UIDB/04469/2020 (strategic fund) granted to E.B.S.info:eu-repo/semantics/publishedVersio

Factors affecting the retention efficiency and physicochemical properties of spray dried lipid nanoparticles loaded with lippia sidoides essential oil

Essential oils (EOs) are widely used in various industrial sectors but can present several instability problems when exposed to environmental factors. Encapsulation technologies are effective solutions to improve EOs properties and stability. Currently, the encapsulation in lipid nanoparticles has received significant attention, due to the several recognized advantages over conventional systems. The study aimed to investigate the influence of the lipid matrix composition and spray-drying process on the physicochemical properties of the lipid-based nanoparticles loaded with Lippia sidoides EO and their retention efficiency for the oil. The obtained spray-dried products were characterized by determination of flow properties (Carr Index: from 25.0% to 47.93%, and Hausner ratio: from 1.25 to 1.38), moisture (from 3.78% to 5.20%), water activity (<0.5), and powder morphology. Zeta potential, mean particle size and polydispersity index, of the redispersed dried product, fell between 25.9 mV and 30.9 mV, 525.3 nm and 1143 nm, and 0.425 and 0.652, respectively; showing slight differences with the results obtained prior to spray-drying (from 16.4 mV to 31.6 mV; 147 nm to 1531 nm; and 0.459 to 0.729). Thymol retention in the dried products was significantly lower than the values determined for the liquid formulations and was affected by the drying of nanoparticles.I.B. acknowledges CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior) for the financial support (88887.368385/2019-00). E.B.S. acknowledges the Portuguese Science and Technology Foundation (FCT) for the funded projects M-ERA-NET/0004/2015 (PAIRED) and UIDB/04469/2020 (strategic fund). WPO acknowledges the São Paulo Research Foundation (FAPESP) for the financial support (Grant N. 2018/26069-0 and 2011/10333-1).info:eu-repo/semantics/publishedVersio

Spouted bed dried Rosmarinus officinalis extract: a novel approach for physicochemical properties and antioxidant activity

In this study, a conical-cylindrical spouted bed dryer with Teflon® beads as spouting material was used for producing powdered rosemary (Rosmarinus officinalis L.) extract. The influence of the inlet drying gas temperature (Tgi) and the percentage ratio between the feed rate of concentrated liquid extract by the maximum evaporation capacity of the spouted bed (Ws/Wmax) on selected physicochemical properties of the finished products were investigated. Antioxidant properties of the concentrated liquid extract and dried extracts were also evaluated by the 2.2-diphenyl-1-picrylhydrazyl radical scavenging (DPPH) and lipid peroxidation induced by Fe2+/citrate (LPO) methods; and compared with the values obtained for a lyophilized extract (used as a control). Colloidal silicon dioxide (Tixosil® 333) and maltodextrin (DE 14) at a 2:1 ratio was added to the concentrated extract before drying (4.4% w/w) to improve the drying performance. The drying variables Ws/Wmax and Tgi have statistically significant influence on total polyphenols and total flavonoid contents of the dried powders. The concentrated extract (on dry basisbeing absolute solid content) showed superior antioxidant activity (AA) compared to both the spouted bed dried and the lyophilized extracts; exhibiting IC50 values of 0.96 ± 0.02, 2.16 ± 0.04 and 3.79 ± 0.05 µg mL1 (DPPH method) and 0.22 ± 0.01, 1.31± 0.01 and 2.54 ± 0.02 µg mL1 (LPO method), respectively. These results of AA are comparable to values obtained for quercetin, a flavonoid compound often used as a reference standard due to its potent antioxidant activity; with IC50 of 1.17 µg mL1 (DPPH) and 0.22 µg mL1 (LPO). However, the dried rosemary extracts are about 13.5 times more concentrated than the initial concentrated extract (dry weight), with a concentration of total flavonoids and polyphenols compounds ranging from 4.3 to 12.3 and from 1.2 to 4.7 times higher than the concentrated extract values (wet basis). The AA per dry product mass was thus significantly higher than the values measured for concentrated extractive solution, irrespective of some losses of AA apparently due to the drying process.Foundation of Research Support of the São Paulo State (FAPESP) for the funded projects 2011/10333-1, 2012/03427-2 and 2018/26069-0 and for the National Council for Scientific and Technological Development (CNPq) for the financial support. E.B.S. acknowledges the Portuguese Science and Technology Foundation (FCT) for the funded projects M-ERA-NET/0004/2015 (PAIRED) and UIDB/04469/2020 (strategic fund)info:eu-repo/semantics/publishedVersio

Natural ergot alkaloids in ocular pharmacotherapy: known molecules for novel nanoparticle-based delivery systems

Several pharmacological properties are attributed to ergot alkaloids as a result of their antibacterial, antiproliferative, and antioxidant effects. Although known for their biomedical applications (e.g., for the treatment of glaucoma), most ergot alkaloids exhibit high toxicological risk and may even be lethal to humans and animals. Their pharmacological profile results from the structural similarity between lysergic acid-derived compounds and noradrenalin, dopamine, and serotonin neurotransmitters. To reduce their toxicological risk, while increasing their bioavailability, improved delivery systems were proposed. This review discusses the safety aspects of using ergot alkaloids in ocular pharmacology and proposes the development of lipid and polymeric nanoparticles for the topical administration of these drugs to enhance their therapeutic efficacy for the treatment of glaucoma.This work was supported by CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior) granted to I.B. (88887.368385/2019-00), by the Portuguese Science and Technology Foundation (FCT) and co-financed by FEDER, under the Partnership Agreement PT2020, granted to E.B.S. (UIDB/04469/2020 strategic fund), by the Nutraceutica come supporto nutrizionale nel paziente oncologico, project granted to A.S. (CUP: B83D18000140007), and by Foundation of Research Support of the São Paulo State (FAPESP) for the funded projects 2011/10333-1, 2012/03427-2, and 2018/26069-0 and for the National Council for Scientific and Technological Development (CNPq) granted to W.P.O.info:eu-repo/semantics/publishedVersio

Technological development and drying of lipid systems containing essential oil of Lippia sidoides

Óleos essenciais (OEs) constituem misturas complexas de várias moléculas voláteis hidrofóbicas produzidas pelo metabolismo secundário de plantas. Eles são empregados em diversos setores industriais, como por exemplo, o farmacêutico, alimentício, cosmético, agricultura e pecuária, em virtude de suas comprovadas ações bactericida, virucida, fungicida, antiparasitária, inseticida, analgésica, sedativa, anti-inflamatória, espasmolitica e anestésica local. Também têm sido utilizados na proteção de alimentos (como antioxidantes e conservantes), e incorporados em embalagens ativas. Os OEs podem apresentar problemas de instabilidade quando expostos ao calor, umidade, oxigênio e luminosidade. A reduzida solubilidade em água e sua elevada volatilidade são outras limitações para seu uso. A microencapsulação e nanoencapsulação dos OEs são estratégias viáveis e eficientes à proteção e modulação da liberação dos compostos bioativos, promovendo o aumento da estabilidade físico-química, proteção contra fatores ambientais, redução da volatilidade, aumento da solubilidade, biodisponibilidade, atividade biológica, redução da toxicidade, entre outros. A encapsulação em carreadores lipídicos micro e nanoestruturados tem recebido significativa atenção nos setores farmacêutico e alimentício, em face de várias vantagens, como baixa toxicidade, facilidade de escalonamento, baixo custo de produção e capacidade de encapsular compostos hidrofílicos e lipofílicos. Este trabalho teve como objetivo estudar a formação e secagem de sistemas lipídicos micro e/ou nanoestruturados contendo óleo essencial de Lippia sidoides, empregando diferentes processos tecnológicos e avaliar a influência destes nas propriedades apresentadas pelo produto líquido e seco obtido (propriedades físico-químicas, estabilidade, atividade antimicrobiana e retenção do timol, composto ativo majoritário no OE). Os resultados mostraram que a composição das formulações, as condições e o processo de secagem tiveram efeitos significativos nas propriedades físico-químicas e na estabilidade do produto, além de influenciarem também a retenção de timol. Este trabalho permitiu obter informações relevantes sobre os processos de secagem das formulações lipídicas por spray drying e liofilização e também sobre as características apresentadas pelos pós obtidosEssential oils (EOs) are complex mixtures of various volatile molecules (hydrophobic) produced by the plants secondary metabolism. Essential oils have high importance in various industrial sectors, such as pharmaceutical, food, cosmetic, health, agriculture and livestock; mainly due to its proved biological activity as bactericidal, virucidal, fungicidal, antiparasitic, insecticidal, analgesic, sedative, anti-inflammatory, spasmolytic and local anesthetic activities. Essential oils have also been used in food protection (as antioxidants and preservatives), and embedded in active food packaging. It is also characteristic of EOs present problems of instability when exposed to heat, moisture, oxygen and light. The reduced water solubility and high volatility are another limitation for the use of EOs. The micro and nanoencapsulation technologies of EOs arises as a viable and effective solution, increasing the product physicochemical stability, furnishing protection against environmental factors, reducing volatility, modulate the release, increasing bioavailability, reducing toxicity, among others. Encapsulation in lipid carriers has received significant attention in the pharmaceutical and food sectors, mainly due to the several attributed advantages such as low toxicity, capability to encapsulate hydrophilic and lipophilic compounds, low production costs and easy scale up. The objective of this work was to study the formation and drying of micro and/or nanostructured lipid systems loaded with essential oil of Lippia sidoides using different technological processes and to evaluate their influence on the properties presented by the liquid and dry product obtained (physicochemical properties, stability, antimicrobial activity and retention of thymol, major active compound in EO). The results showed that the composition of the formulations, the conditions and the drying process had significant effects on the physicochemical properties and the stability of the product, besides also influencing the retention of thymol. This work allowed to obtain relevant information on the drying processes of the lipid formulations by spray and freeze drying and also on the characteristics presented by the obtained powder

Nanostructured Lipid Carriers Loaded with Lippia sidoides Essential Oil as a Strategy to Combat the Multidrug-Resistant Candida auris

The emerging pathogen Candida auris&nbsp;is an emerging fungal pathogen that was associated with nosocomial infectious outbreaks. Its worldwide incidence and the emerging multidrug-resistant strains highlight the urgency for novel and effective antifungal treatment strategies. Lippia sidoides essential oil (LSEO) proved antifungal activity, including anti-Candida. However, it may undergo irreversible changes when in contact with external agents without adequate protection. Herein, we encapsulated LSEO in nanostructured lipid carriers (NLC) through the hot emulsification method followed by sonication. NLC matrix was based on oleic acid and Compritol&reg; 888, or a combination of carnauba wax and beeswax, stabilized by sodium dodecyl sulfate. Eight formulations were produced and characterized by the determination of the particle size (213.1 to 445.5 nm), polydispersity index (around 0.3), and &zeta;-potential (&minus;93.1 to &minus;63.8 mV). The antifungal activity of nanoparticles and LSEO against C. auris and the in vivo toxicity in Galleria mellonella model were also evaluated. Both NLC and LSEO exhibited potent activity against the yeast, with Minimum Inhibitory Concentration between 281 and 563 &micro;g/mL, and did not evidence toxicity in the in vivo model. Therefore, this study confirms the viability of NLCs loaded with LSEO in combating drug-resistant pathogens as a potential new therapeutic strategy for managing of candidemia

Spray-Dried Structured Lipid Carriers for the Loading of Rosmarinus officinalis: New Nutraceutical and Food Preservative

Rosemary, an aromatic herb with significant antioxidative activity, is frequently used as food preservative and a source of nutraceuticals. Its antioxidant effect is mainly related to the presence of phenolic compounds, molecules considerably unstable and prone to irreversible physicochemical changes when exposed to external agents. We here proposed the loading of rosemary into structured lipid systems to improve its physicochemical properties. Four formulations were prepared using the same amount of rosemary lyophilized extract. The lipid phase was composed of stearic acid and oleic acid, and the aqueous phase, a varying combination of drying carriers (whey protein concentrate or gum Arabic) and surfactant (Poloxamer 188). The formulations were sonicated, spray-dried, and the obtained powders were characterized regarding the density (0.18 g/mL to 0.26 g/mL), particle size distribution (7 &micro;m and 52 &micro;m), and water solubility (29% to 48%). The antioxidant activity was determined by applying ABTS&bull;+ radical-scavenging assay and the results expressed per gram of lyophilized extract (150.6 &mu;mol Trolox/g to 376.4 &mu;mol Trolox/g), with a significantly lower/higher result seen for formulations containing gum Arabic and a higher concentration of Poloxamer. The prepared systems may have potential applications as preservative in foodstuff and as nutraceutical

Formação, caracterização e atividade biológica de sistemas lipídicos contendo óleo essencial

Essential oils (EOs) have aroused great interest in recent years, mainly due to their wide range of biological activities, such as antifungal, antibacterial, insecticide, antiviral, antioxidant, among others. Its use as an active ingredient brings countless benefits, and maybe the main advantage is related to its ability to fight the resistance often presented by microorganisms against antibiotics and antifungals available on the market. However, the high volatility and sensitivity of these compounds restrict their use, limiting the incorporation into more elaborate products. Microencapsulation and nanoencapsulation of EOs emerge as viable and efficient strategies to protect and modulate the release of their bioactive compounds, promoting increased physical-chemical stability, protection against environmental factors, reduced volatility, increased solubility, bioavailability and biological activity, reduction of toxicity, among other benefits. Lipid systems are an especially promising strategy for EO incorporation, as they are biocompatible, present high loading capacity, low cost, low toxicity, and can encapsulate both lipophilic and hydrophilic substances. Among these systems, the liposomes are biocompatible, biodegradable vesicles with a potential pharmaceutical application; and nanostructured lipid carriers (NLC) are nanoparticles able to carry chemically different molecules, providing an adjustable release profile, which can be produced on a large scale, without the need for organic solvents. The influence of the encapsulation system, lipid components, type of emulsifier, and other excipients must be evaluated to optimize system stability, retention of bioactive compounds, and improve their biological activity. This thesis aimed to investigate the technological routes involved in obtaining micro or nanostructured lipid systems to stabilize and modulate the release of rosemary-pepper (Lippia sidoides) and clove (Syzygium aromaticum) essential oils were investigated, emphasizing the preparation processes, physicochemical properties, stability, and biological activity against multidrugresistant microorganisms of clinical importance. The main formulation and process variables were analyzed, defining optimal processing conditions for liposome-based systems encapsulating essential oil complexed in &beta;-cyclodextrin and for NLCs. Assays of antifungal activity against different microorganisms were performed for NLCs, which proved to be efficient in combating the multidrug-resistant fungus Candida auris, which has spread globally, mainly in hospital environments, with very limited or non-existent treatment options.Óleos essenciais (OEs) têm despertado grande interesse nos últimos anos, principalmente devido a sua ampla gama de atividades biológicas, como antifúngicos, antibacterianos, inseticidas, antivirais, antioxidantes, entre outras. Seu uso como ingrediente ativo traz uma série de benefícios, e talvez a principal vantagem esteja relacionada à sua capacidade de combater a resistência muitas vezes apresentada pelos microrganismos contra os antibióticos e antifúngicos disponíveis no mercado. Contudo, sua alta volatilidade e sensibilidade restringem seu uso e limitam sua incorporação a produtos mais elaborados. A microencapsulação e nanoencapsulação dos OEs surgem como estratégias viáveis e eficientes à proteção e modulação da liberação de seus compostos bioativos, promovendo o aumento da estabilidade físico-química, proteção contra fatores ambientais, redução da volatilidade, aumento da solubilidade, biodisponibilidade e atividade biológica, redução da toxicidade, entre outros benefícios. Os sistemas lipídicos são uma estratégia especialmente promissora para incorporação de OEs, pois são biocompatíveis, apresentam alta capacidade de carga, baixo custo, baixa toxicidade e são capazes de encapsular tanto substâncias lipofílicas quanto hidrofílicas. Dentre esses sistemas, temos os lipossomas, que são vesículas biocompatíveis, biodegradáveis e com potencial aplicação farmacêutica, e os carreadores lipídicos nanoestruturados (NLC), nanopartículas capazes de carregar moléculas quimicamente diferentes e fornecer um perfil de liberação ajustável, podendo ser produzidas em larga escala e sem a necessidade de solventes orgânicos. A influência do sistema de encapsulação, componentes lipídicos, tipo de emulsificante e outros excipientes deve ser avaliada para otimizar a estabilidade do sistema, a retenção de compostos bioativos e melhorar sua atividade biológica. Nesta tese se investigou várias rotas tecnológicas envolvidas na obtenção de sistemas lipídicos micro ou nanoestruturados para estabilizar e modular a liberação dos óleos essenciais alecrim-pimenta (Lippia sidoides) e cravo (Syzygium aromaticum), enfatizando-se processos de preparação, propriedades físico-químicas, estabilidade e atividade biológica frente a microrganismos multirresistentes de importância clínica. As principais variáveis de formulação e de processo foram analisadas, sendo definidas condições ótimas de processamento para sistemas a base de lipossomas encapsulando óleo essencial complexado em &beta;-ciclodextrina e para os NLCs. Ensaios de atividade antifúngica frente a diferentes microrganismos foram realizados para os NLCs, que se mostraram eficientes no combate do fungo multirresistente Candida auris, que tem se disseminado globalmente principalmente em ambientes hospitalares, para o qual as opções de tratamento são muito reduzidas ou inexistentes

Perfil Metabolômico Em Pacientes Com Anemia Hemolítica Autoimune

Introduction: Autoimmune Hemolytic Anemia (Aiha) Is A Rare Clinical Condition With Hemolysis Mediated By Immunoglobulin Binding On The Surface Of Erythrocytes With Or Without Complement Activation. Metaboloma Is The Sum Of The Genetic Configuration Of An Organism To The External Factors. The Metabolic Profile Involved In Aiha Has Not Yet Been Described And May Be The Key To New Findings About The Mechanism Of Autoimmune Hemolysis. Objectives: To Describe A Profile Of Aiha Related Metabolites, Increased Hemolysis And Risk Of Relapse. Patients And Method: We Analyzed The Plasma From 31 Patients With Primary Aiha Compared To Plasma From 150 Healthy Subjects Using Mass Spectrometry (Kit Absoluteidq P180, Biocrates, Austria). The Statistical Analysis Was Performed By The Software Available At Http://Www.Metaboanalyst.Ca/. Results: Of The 95 Metabolites Found In Patients With Aiha, Four Acylcarnitines, Two Phosphatidylcholines (Pc), Asymmetric Dimethylarginine (Adma) And Three Sphingomyelins Were Increased With GreIntrodução: A Anemia Hemolítica Autoimune (Ahai) É Uma Condição Clínica Rara Com Hemólise Mediada Pela Fixação De Imunoglobulinas Na Superfície Dos Eritrócitos Com Ou Sem Ativação Do Complemento. Metaboloma É A Soma Da Configuração Genética De Um Organismo Com Os Fatores Externos. O Perfil Metabolômico Envolvido Na Ahai Ainda Não Foi Descrito E Pode Ser A Chave De Novas Descobertas Acerca Do Mecanismo De Hemólise Autoimune. Objetivos: Descrever Um Perfil De Metabólitos Relacionados À Ahai, Maior Hemólise E Risco De Recaída. Casuística E Método: Analisamos O Plasma De 31 Pacientes Com Ahai Primária Comparados Ao Plasma De 150 Indivíduos Saudáveis Utilizando A Espectrometria De Massa (Kit Absoluteidq P180, Biocrates, Áustria). A Análise Estatística Foi Realizada Pelo Software Disponível No Site Http://Www.Metaboanalyst.Ca/. Resultados: Dos 95 Metabólitos Encontrados Nos Pacientes Com Ahai, Quatro Acilcarnitinas, Duas Fosfatidilcolinas (Pc), Dimetilarginina Assimétrica (Adma) E Três Esfingomielinas Estavam AumenDados abertos - Sucupira - Teses e dissertações (2018

Cyclodextrins-in-liposomes: a promising delivery system for Lippia sidoides and Syzygium aromaticum essential oils

Biological activity of essential oils (EOs) has been extensively reported; however, their low aqueous solubility, high photosensitivity, and volatility compromise a broad industrial use of these compounds. To overcome these limitations, we proposed a nanoencapsulation approach to protect EOs, that aims to increase their stability and modulate their release profile. In this study, drug-in-cyclodextrin-in-liposomes encapsulating two essential oils (Lippia sidoides and Syzygium aromaticum) and their respective major compounds (thymol and eugenol) were produced by ethanol injection and freeze-dried to form proliposomes and further physicochemically characterized. Liposomes showed high physical stability over one month of storage at 4 °C, with slight changes in the mean size, polydispersity index (PDI), and zeta potential. Reconstituted proliposomes showed a mean size between 350 and 3300 nm, PDI from 0.29 to 0.41, and zeta potential between −22 and −26 mV. Differential scanning calorimetry and X-ray diffraction of proliposomes revealed a less-ordered crystalline structure, leading to high retention of the major bioactive compounds (between 73% and 93% for eugenol, and 74% and 84% for thymol). This work highlights the advantages of using drug-in-cyclodextrin-in-liposomes as delivery systems to retain volatile compounds, increasing their physicochemical stability and their promising potential to be utilized as carriers in products in the pharmaceutical, food, and cosmetic industries.Authors received funding from The State of São Paulo Research Foundation (FAPESP) for sponsorship of the project No. 2018/26069-0; from the Coordination of Superior Level Staff Improvement (CAPES) for the fellowship of the first author. The authors also acknowledge the Portuguese Science and Technology Foundation, Ministry of Science and Education (FCT/MEC) for national funds co-financed by FEDER, under the Partnership Agreement PT2020 for the granted project UIDB/04469/2020 (strategic fund).info:eu-repo/semantics/publishedVersio