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This study aimed to develop microemulsions (MEs) containing α-bisabolol for the topical treatment of cutaneous leishmaniasis (CL). Initially, pseudoternary phase diagrams were developed using α-bisabolol as the oil phase, Eumulgin® CO 40 as the surfactant, Polymol® HE as the co-surfactant, and distilled water as the aqueous phase. Two transparent liquid systems (TLS) containing 5% of α-bisabolol were selected and characterized (F5E25 and F5EP25). Next, skin permeation and retention assays were performed using Franz cells. The interaction of the formulation with the stratum corneum (SC) was evaluated using the FTIR technique. The cytotoxicity was evaluated in murine peritoneal macrophages. Finally, the antileishmanial activity of microemulsions was determined in promastigotes and amastigotes of L. amazonensis (strain MHOM/BR/77/LTB 0016). As a result, the selected formulations showed isotropy, nanometric size (below 25 nm), Newtonian behavior and pH ranging from 6.5 to 6.9. The MEs achieved a 2.5-fold increase in the flux and skin-permeated amount of α-bisabolol. ATR-FTIR results showed that microemulsions promoted fluidization and extraction of lipids and proteins of the stratum corneum, increasing the diffusion coefficient and partition coefficient of the drug in the skin. Additionally, F5E25 and F5EP25 showed higher activity against promastigotes (IC50 13.27 and 18.29, respectively) compared to unencapsulated α-bisabolol (IC50 53.8). Furthermore, F5E25 and F5EP25 also showed antileishmanial activity against intracellular amastigotes of L. amazonensis, with IC50 50 times lower than free α-bisabolol and high selectivity index (up to 15). Therefore, the systems obtained are favorable to topical administration, with significant antileishmanial activity against L. amazonensis promastigotes and amastigotes, being a promising system for future in vivo trials.
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Emulsões , Macrófagos Peritoneais , Sesquiterpenos Monocíclicos , Sesquiterpenos , Pele , Animais , Sesquiterpenos Monocíclicos/farmacologia , Sesquiterpenos Monocíclicos/química , Emulsões/química , Camundongos , Sesquiterpenos/farmacologia , Sesquiterpenos/química , Pele/parasitologia , Macrófagos Peritoneais/efeitos dos fármacos , Macrófagos Peritoneais/parasitologia , Leishmaniose Cutânea/tratamento farmacológico , Leishmaniose Cutânea/parasitologia , Espectroscopia de Infravermelho com Transformada de Fourier , Absorção Cutânea/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Feminino , Leishmania/efeitos dos fármacos , Tensoativos/farmacologia , Tensoativos/química , Antiprotozoários/farmacologia , Antiprotozoários/químicaRESUMO
D-limonene, derived from citrus essential oils, holds significant therapeutic potential but faces challenges due to its high volatility, especially in pharmaceutical formulations. This study investigates microemulsions as a promising delivery system for volatile compounds, emphasizing their thermal protection for D-limonene. The formulation development was guided by a pseudo-ternary phase diagram and involved assays with different surfactants. Microemulsions were achieved solely with Labrasol® (Gattefossé Brasil, São Paulo, Brazil), encompassing concentrations of 7.1% to 30.8% D-limonene, 28.6% to 57.1% Labrasol®, and 20.0% to 64.3% water. All formulations were homogeneous, transparent, and presented low viscosity, with adequate D-limonene content, indicating that the production is feasible at room temperature. While the formulations demonstrated robust physical stability under mechanical stress, they exhibited destabilization at temperatures exceeding 50 °C. In terms of oxidative stability, pure D-limonene exhibited an induction period of 4.88 min, whereas microemulsions extended this period by four to eight times. Notably, the induction period of the microemulsions remained practically unchanged pre and post-heating (70 °C), suggesting the formulation's ability to enhance the D-limonene thermal stability. This highlights the value of oxidative stability analysis as a quicker tool than conventional oxidative tests, while affirming microemulsions as a viable encapsulation strategy for D-limonene protection against elevated temperatures.
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Microemulsions are important for soil and sediment remediation technology. The characteristics of the surfactants that make up these microemulsions include low sorption into soil or sediments, low surface and interfacial tension, the ability to penetrate tiny pores, and good solubilization of contaminants. This review revealed that microemulsions formulated with nonionic and anionic surfactants have higher recovery efficiencies for hydrophobic contaminants than cationic ones, as evidenced by the surveyed studies reporting effective remediation of soils and sediments using on microemulsions. These microemulsified systems have been found to remove petroleum and its derivatives from soil or sediments at percentages ranging from 40 to 100%. As such, this review can aid with the choice of surfactants used in microemulsions for remediation, such as those with plant-based components, which are promising solutions for the remediation of contaminated soils due to their contaminant extraction efficiency and biodegradability.
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Petróleo , Poluentes do Solo , Tensoativos/química , Solo , Poluentes do Solo/análise , Poluição AmbientalRESUMO
Lecithins are a phospholipid-rich mixture recovered from the degumming process of crude vegetable oils. Since the nineteenth century, this by-product of oil processing has been used as a food and pharmaceutical ingredient. Lecithins' popularity as an ingredient in the pharmaceutical and food industries arises from their particular properties, such as their hydrophilic-lipophilic balance, critical micellar concentration, and assembly properties. However, there is limited knowledge of the use of lecithins to formulate pharmaceutical- and food-grade microemulsions. Unlike conventional emulsions, microemulsions are thermodynamically stable systems that offer long-term stability. Besides, microemulsions show nano-sized droplets, transparency, ease of preparation and scale-up, and do not require expensive equipment. This review aims to provide a comprehensive overview of lecithins, their properties, and their use in formulating microemulsions, a promising method to incorporate, protect, and deliver bioactive compounds in pharmaceutical and food products. PRACTICAL APPLICATIONS: Lecithins are a phospholipid-rich mixture recovered from the degumming process of crude vegetable oils. Since the nineteenth century, this by-product of oil processing has been used as a food ingredient. Lecithin phospholipids are commonly used as emulsifier agents in the food and pharmaceutical industries because of their particular properties. However, there is limited knowledge of the use of lecithins to formulate pharmaceutical- or food-grade microemulsions. Unlike conventional emulsions, microemulsions are stable systems that offer long-term stability, nano-sized droplets, transparency, ease of preparation and scale-up, and do not require expensive equipment. This review aims to provide a comprehensive overview of lecithins, their properties, and their use in formulating microemulsions, a promising method to incorporate, protect, and deliver bioactive compounds such as vitamins, flavors, antioxidants, nutrients, colors, antimicrobials, and polyphenols.
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Lecitinas , Óleos de Plantas , Emulsões , Tamanho da Partícula , FosfolipídeosRESUMO
Nifedipine is a potent anti-hypertensive, which is poorly orally bioavailable on account of first-pass metabolism, short half-life, and low water solubility. This study aimed to develop a microemulsified system with low surfactant concentration and to evaluate the influence of microemulsion (ME) phase behavior on skin permeation of nifedipine, as drug model. Thereafter, MEs were obtained using PPG-5-CETETH-20, oleic acid, and phosphate buffer at pH 5.0. The selected MEs were isotropic, with droplet diameters less than 10 nm, polydispersity index < 0.25, and pH between 5.0 and 5.2. MEs presented low viscosity and Newtonian behavior. SAXS results confirmed bicontinuous and oil-in-water (o/w) MEs formation. The presence of the drug promoted only very slight modifications in the ME structure. The MEs presented ability to deliver nifedipine via the transdermal route when in comparison with the control. Nevertheless, the skin permeated and retained amounts from the o/w and bicontinuous formulations did not differ significantly. The ATR-FTIR demonstrated that both formulations promoted fluidization and disorganization of lipids and increased the drug diffusion and partition coefficients in the skin. In conclusion, PPG-5-CETETH-20 MEs obtained proved to be effective skin permeation enhancers, acting by rising the coefficients of partition and diffusion of the nifedipine in the skin.
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Nifedipino , Pele , Administração Cutânea , Emulsões/química , Nifedipino/metabolismo , Espalhamento a Baixo Ângulo , Pele/metabolismo , Tensoativos/química , Água/química , Difração de Raios XRESUMO
The impetus for the expanding interest in ionic liquids (ILs) is their favorable properties and important applications. Ionic liquid-based surfactants (ILBSs) carry long-chain hydrophobic tails. Two or more molecules of ILBSs can be joined by covalent bonds leading, e.g., to gemini compounds (GILBSs). This review article focuses on aspects of the chemistry and applications of ILBSs and GILBSs, especially in the last ten years. Data on their adsorption at the interface and micelle formation are relevant for the applications of these surfactants. Therefore, we collected data for 152 ILBSs and 11 biamphiphilic compounds. The head ions of ILBSs are usually heterocyclic (imidazolium, pyridinium, pyrrolidinium, etc.). Most of these head-ions are also present in the reported 53 GILBSs. Where possible, we correlate the adsorption/micellar properties of the surfactants with their molecular structures, in particular, the number of carbon atoms present in the hydrocarbon "tail". The use of ILBSs as templates for the fabrication of mesoporous nanoparticles enables better control of particle porosity and size, hence increasing their usefulness. ILs and ILBSs form thermodynamically stable water/oil and oil/water microemulsions. These were employed as templates for (radical) polymerization reactions, where the monomer is the "oil" component. The formed polymer nanoparticles can be further stabilized against aggregation by using a functionalized ILBS that is co-polymerized with the monomers. In addition to updating the literature on the subject, we hope that this review highlights the versatility and hence the potential applications of these classes of surfactants in several fields, including synthesis, catalysis, polymers, decontamination, and drug delivery.
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Poorly soluble active pharmaceutical ingredients (APIs) create major problems in drug dosage form formulation resulting in significant delays in drug pharmaceutical screening, impairing the drug dosage form production. Aiming to minimize the use of excipients for increasing drug apparent solubility and, as a result, its bioavailability, exploration of innovative approaches is an earnest need. Microemulsion is an alternative drug delivery system that emerged as a valuable tool to achieve safe formulations for insoluble compounds and to improve their biopharmaceutical properties and pharmacokinetics. This review aims to present the state of the art of microemulsion systems, bringing an overview about their origin and how they can be properly produced and thoroughly characterized by different approaches. Furthermore, comments on regulatory issues regarding stability assessment and toxicity evaluation are discussed. The review concludes with a current opinion on microemulsion systems. The overall objective of this work was to describe all the potentialities of microemulsion systems as a drug carrier for therapeutic purposes, highlighting the unique features of this nanotechnological platform. Display Image.
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Sistemas de Liberação de Medicamentos , Excipientes , Disponibilidade Biológica , Sistemas de Liberação de Medicamentos/métodos , Emulsões , Solubilidade , TensoativosRESUMO
Essential oils (EOs) have demonstrated antimicrobial activity against bacteria due to the effects of their major components. The direct application of EOs may present a rapid volatilization of its components and can decrease their effectiveness. Encapsulation by means of emulsification can provide protection to lipid compounds on a microscale. The aim of this study was to characterize microemulsions of cinnamon essential oil (CEO), oregano essential oil (OEO), and rosemary essential oil (REO) prepared by high-frequency ultrasound and evaluate their antimicrobial activities against Escherichia coli and Listeria monocytogenes. The microemulsions (oil-in-water, O/W) of EOs were prepared using high-frequency ultrasound, applying a wave amplitude of 84 µm for 15 min (REO and CEO) or 30 min (OEO). The antimicrobial activity was determined by inoculating 108 CFU/mL of bacteria. Nonsurvival of the bacteria was confirmed by plate count in tryptic soy agar, determining the minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC). The microemulsions exhibited droplet size diameters of 1.98 to 5.46 µm, showing high encapsulation efficiencies (79.91-81.97%) and low separation rates (2.50-6.67%). The MIC and MBC for the microemulsions for both bacteria were 20-75% less than values obtained for the non-encapsulated EOs. This study demonstrates that high-frequency ultrasound is a suitable technique for obtaining stable microemulsions to deliver natural antimicrobials that can be applied to control bacteria of high relevance in food safety.
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INTRODUCTION: There is a clinical need for pharmaceutical dosage forms devised to prolong the acting time of local anesthetic (LA) agents or to reduce their toxicity. Encapsulation of LA in drug delivery systems (DDSs) can provide long-term anesthesia for inpatients (e.g. in immediate postsurgical pain control, avoiding the side effects from systemic analgesia) and diminished systemic toxicity for outpatients (in ambulatory/dentistry procedures). The lipid-based formulations described here, such as liposomes, microemulsions, and lipid nanoparticles, have provided several nanotechnological advances and therapeutic alternatives despite some inherent limitations associated with the fabrication processes, costs, and preclinical evaluation models. AREAS COVERED: A description of the currently promising lipid-based carriers, including liposomes, microemulsions, and nanostructured lipid carriers, followed by a systematic review of the existing lipid-based formulations proposed for LA. Trends in the research of these LA-in-DDS are then exposed, from the point of view of administration route and alternatives for non-traditionally administered LA molecules. EXPERT OPINION: Considering the current state and potential future developments in the field, we discuss the reasons for why dozens of formulations published every year fail to reach clinical trials; only one lipid-based formulation for the delivery of local anesthetic (Exparel®) has been approved so far.
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Anestésicos Locais/administração & dosagem , Sistemas de Liberação de Medicamentos , Lipídeos/química , Anestesia Local/métodos , Animais , Portadores de Fármacos/química , Humanos , Lipossomos , Nanopartículas/administração & dosagem , NanoestruturasRESUMO
In this work, several normal, oil-in-water (o/w) microemulsions (MEs) were prepared using peppermint essential oil, jojoba oil, trans-anethole, and vitamin E as oil phases to test their capacity to load paclitaxel (PTX). Initially, pseudo-ternary partial phase diagrams were constructed in order to find the normal microemulsion region using d-α-tocopherol polyethylene glycol 1000 succinate (TPGS-1000) as surfactant and isobutanol (iso-BuOH) as co-surfactant. Selected ME formulations were loaded with PTX reaching concentrations of 0.6 mg mL-1 for the peppermint oil and trans-anethole MEs, while for the vitamin E and jojoba oil MEs, the maximum concentration was 0.3 mg mL-1. The PTX-loaded MEs were stable according to the results of heating-cooling cycles and mechanical force (centrifugation) test. Particularly, drug release profile for the PTX-loaded peppermint oil ME (MEPP) showed that â¼ 90% of drug was released in the first 48 h. Also, MEPP formulation showed 70% and 90% viability reduction on human cervical cancer (HeLa) cells after 24 and 48 h of exposure, respectively. In addition, HeLa cell apoptosis was confirmed by measuring caspase activity and DNA fragmentation. Results showed that the MEPP sample presented a major pro-apoptotic capability by comparing with the unloaded PTX ME sample.