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1.
J Neurochem ; 168(8): 1655-1683, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38923542

RESUMO

Parkinson's disease (PD) is the second most common neurodegenerative disorder. The primary pathological features of PD include the presence of α-synuclein aggregates and Lewy bodies, mitochondrial dysfunction, oxidative stress, and neuroinflammation. Recently, omega-3 fatty acids (ω-3 PUFAs) have been under investigation as a preventive and/or therapeutic strategy for PD, primarily owing to their antioxidant and anti-inflammatory properties. Therefore, the objective of this study was to conduct a systematic review of the literature, focusing on studies that assessed the effects of ω-3 PUFAs in rodent models mimicking human PD. The search was performed using the terms "Parkinson's disease," "fish oil," "omega 3," "docosahexaenoic acid," and "eicosapentaenoic acid" across databases PUBMED, Web of Science, Science Direct, Scielo, and Google Scholar. Following analysis based on predefined inclusion and exclusion criteria, 39 studies were included. Considering behavioral parameters, pathological markers of the disease, quantification of ω-3 PUFAs in the brain, as well as anti-inflammatory, antioxidant, and anti-apoptotic effects, it can be observed that ω-3 PUFAs exhibit a potential neuroprotective effect in PD. In summary, this systematic review presents significant scientific evidence regarding the effects and mechanisms underlying the neuroprotective properties of ω-3 PUFAs, offering valuable insights for the development of future clinical investigations.


Assuntos
Ácidos Graxos Ômega-3 , Doença de Parkinson , Animais , Ácidos Graxos Ômega-3/farmacologia , Ácidos Graxos Ômega-3/uso terapêutico , Doença de Parkinson/metabolismo , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/patologia , Humanos , Modelos Animais de Doenças
2.
J Biol Chem ; 298(7): 101975, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35489470

RESUMO

Around the world, many couples have turned to in vitro fertilization as a viable solution to fertility issues. Low-density lipoprotein (LDL) is a protein best known for transporting fat molecules throughout the body, but it has also been shown to protect sperm cells during cryopreservation due to its micellar structure. In the present study, we aimed to evaluate different protocols for the preparation of nanoparticles from egg yolk plasma (EYP) containing LDL to improve the viability of cryopreserved canine semen. EYP was subjected to three distinct treatments: ultrasonification in an ultrasound bath at 40 kHz for 30 min (LDL-B); ultrasonification via an ultrasound probe at 50% amplitude for 30 min (LDL-P); and high-pressure homogenization at 10,000 PSI for six cycles (LDL-H). Sperm quality was assessed after thawing using computer-assisted sperm analysis and flow cytometry. The results revealed that compared to the EYP control, the LDL-P formulation presented significantly higher efficiency (p < 0.05) in maintaining total and progressive sperm motility, sperm membrane integrity and fluidity, and levels of intracellular reactive oxygen species. The LDL-P nanoparticles had an average size of approximately 250 nm, a PDI value of 0.3, and -1.15 mV of zeta potential, which are very important because it is an indicator of the stability of a colloidal dispersion. Therefore, we conclude that ultrasonication of EYP using a probe is an efficient method for the preparation of LDL nanoparticles that would enhance the cryoprotection of semen during freezing.


Assuntos
Crioprotetores , Gema de Ovo , Lipoproteínas LDL , Nanopartículas , Preservação do Sêmen , Animais , Crioprotetores/análise , Cães , Gema de Ovo/química , Lipoproteínas LDL/química , Masculino , Sêmen , Preservação do Sêmen/métodos , Preservação do Sêmen/veterinária , Motilidade dos Espermatozoides , Espermatozoides
3.
Int J Environ Health Res ; 32(1): 168-180, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32200653

RESUMO

Bioactive compounds, synthesized by photosynthetic microorganisms, have drawn the attention of the pharmaceutical field. This study aimed at evaluating synthesis and in vitro antioxidant capacity of phenolic compounds produced by a microalgae species P. boryanum, which was grown in six different culture media (standard BG11, modified BG11/MBG11, standard WC, modified WC, WC*2 and basal). The highest concentrations of biomass (1.75 ± 0.01 g.L-1) and phenolic content (3.18 ± 0.00 mg.g-1) were obtained when P. boryanum was grown in MBG11 and phenolic acids were identified: gallic, protocatechuic, chlorogenic, hydroxybenzoic and vanillic ones. All extracts exhibited scavenger activity in the ABTS assay and inhibited peroxidase. However, phenolic compounds from P. boryanum grown in BG11 and MBG11 had the most potent scavenger activity in the DPPH assay. In sum, P. boryanum can be a new source of free phenolic compounds with potential antioxidant activity when grown in MBG11, since it yields high amounts of biomass and phenolic compounds.


Assuntos
Antioxidantes , Clorofíceas/química , Fenóis , Biomassa , Fenóis/análise , Extratos Vegetais
4.
Drug Chem Toxicol ; 44(6): 585-594, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31476915

RESUMO

Lipid nanocarriers (LNs), for example nanoemulsions (NE), are an emerging tool for drug delivery due to their ability to incorporate drugs, protect the drug from degradation, improve bioavailability, and control release. Although LNs are widely studied and applied, especially in the pharmaceutical field, knowledge about their toxicity is scarce. Moreover, the majority of studies focus on their efficiency rather than safety. Thus, the aim of this study was to evaluate the possible toxic effects of NE in vivo. Male Wistar rats (2 months old, 250 g) were treated once daily for 21 days with NE via oral or intraperitoneal delivery at 200, 400 or 800 mg lipid/kg body weight. At the end of the experiment, biochemical, hematological, oxidative stress, and genotoxicity parameters were analyzed. Our results showed that treatment with NE did not modify organ weight or biochemical parameters when compared to controls. The highest NE dose (800 mg/kg) via intraperitoneal injection caused changes in hematological parameters, namely increased plasma proteins, platelets, total leukocytes, and neutrophils, findings that suggest an inflammatory reaction. Further, the same dose evoked lipid peroxidation in the liver. Taken together, the results from this study suggest that NEs can be considered safe for oral administration, but high doses via the parenteral route can cause toxic effects. This study contributes to knowledge about NE toxicity and provides important data about their safe use in the pharmaceutical field.


Assuntos
Sistemas de Liberação de Medicamentos , Preparações Farmacêuticas , Administração Oral , Animais , Lipídeos , Masculino , Ratos , Ratos Wistar
5.
Pharm Res ; 33(4): 983-93, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26687116

RESUMO

PURPOSE: This study evaluates the advantage of the quercetin encapsulation in nanosized emulsion (QU-NE) administered orally in rats in order to demonstrate its anti-oedematous and antioxidant effects as well as its toxicity. METHODS: The nanocarriers were prepared using the hot solvent diffusion with the phase inversion temperature methods. The nanocarriers physicochemical properties were then investigated. The anti-edematous activity was tested using paw edema in rats. In addition, NF-kB expression in subcutaneous tissue of the paws was accessed by immunohistochemistry while the lipid peroxidation was analyzed in the liver by malondialdehyde reaction with thiobarbituric acid. Hematological, renal and hepatic toxicity as well as the genetic damage were also evaluated. RESULTS: The results demonstrated that QU-NE exhibited pronounced anti-oedematous property comparable to drug diclofenac. This effect was associated with NF-κB pathway inhibition. The lipid peroxidation was also only reduced in rats treated with QU-NE. Besides this, no genetic damage, hematological, renal or hepatic toxicities were observed after administration of QU-NE. CONCLUSIONS: These results suggest that quercetin nanosized emulsion exhibits anti-oedematous and antioxidant properties and does not demonstrate toxic effects. This indicates that it has a potential application in the treatment of inflammatory diseases.


Assuntos
Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/uso terapêutico , Portadores de Fármacos/química , Emulsões/química , Lipídeos/química , Quercetina/administração & dosagem , Quercetina/uso terapêutico , Animais , Anti-Inflamatórios/farmacocinética , Anti-Inflamatórios/toxicidade , Antioxidantes/administração & dosagem , Antioxidantes/farmacocinética , Antioxidantes/uso terapêutico , Antioxidantes/toxicidade , Células CACO-2 , Edema/tratamento farmacológico , Edema/patologia , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Masculino , NF-kappa B/análise , NF-kappa B/antagonistas & inibidores , Quercetina/farmacocinética , Quercetina/toxicidade , Ratos , Ratos Wistar
6.
J Nanosci Nanotechnol ; 16(1): 1050-9, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27398568

RESUMO

Polymer nanofibers are nanomaterials that can be used as scaffolds in tissue engineering. The objective of this study was to develop, characterize and evaluate the in vitro degradation of a biomaterial consisting of nanofibers produced from biodegradable and biocompatible polymers with potential applications as a scaffold for tissue regeneration and containing Spirulina sp. LEB 18 biomass as the bioactive compound. The polymers used were poly(hydroxybutyrate-co-hydroxyvalerate) and polycaprolactone. The polymeric solutions exhibited sufficiently high viscosity to produce uniform nanofibers with diameters between 335 and 617 nm. The applied conditions were as follows: a voltage of 25 kV, a distance from the capillary to the collector of 120 mm, a capillary diameter of 0.80 mm, and 12% polycaprolactone and a blend of 5% polycaprolactone and 10% poly(hydroxybutyrate-co-hydroxyvalerate). The biomass was incorporated into the nanofibers at a concentration of 3%, and the incorporation was confirmed using confocal microscopy. The nanofibers were characterized using differential scanning calorimetry and thermogravimetric analysis, which showed that the addition of biomass did not alter the thermal properties of the biomaterial. The addition of biomass improved the tensile strength and elongation of the scaffolds compared with those produced with polymers alone. A biodegradation assay showed enzymatic action toward the biomaterial, simulating the behavior of natural tissue. Based on the analysis, it was concluded that the scaffolds that were produced have the potential to be applied in the field of tissue regeneration as biomaterials with pharmacological properties.


Assuntos
Biomassa , Nanofibras/economia , Poliésteres/química , Spirulina/química , Catálise , Alicerces Teciduais/química
7.
J Nanosci Nanotechnol ; 16(2): 1275-81, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27433577

RESUMO

Quercetin is a natural compound that has several biological activities including anticancer activity. However, the use of this drug has been limited mostly because of its poor water solubility and low bioavailability. Therefore, the development of quercetin-loaded nanocarrier systems may be considered a promising advance to exploit its therapeutic properties in clinical setting including cancer treatment. This study evaluates the effect of orally administered nanosized emulsion containing quercetin (QU-NE) on the cytotoxicity activity against B16-F10 cells in vitro, and on subcutaneous melanoma in mice inoculated with B16-F1O cells. In vivo experiments, also evaluate the co-administration of quercetin with cisplatin in order to predict synergic effects and the renal and hepatic toxicity. The nanocarriers were prepared through the hot solvent diffusion associated with the phase inversion temperature methods. In vitro study showed reduction of cell viability in a concentration-depend manner for free quercetin and QU-NE. In vivo study, quercetin either as a free drug or colloidal dispersion was administrated at a dose of 5 mg kg(-1) twice a week for 17 days via oral route. Cisplatin was administrated at dose of 1 mg kg(-1) once a week intraperitoneally. Free quercetin and QU-NE reduced tumor growth, however, the reduction observed for QU-NE (P < 0.001 vs. control) was significantly higher than free quercetin (P < 0.05 vs. control). The association of both drugs did not show synergic effect. Besides, no renal or hepatic toxicities were observed after administration of free quercetin and QU-NE. These results suggest that an improvement in the oral bioavailability of quercetin occurred when this compound was dissolved in the oily phase of a nanosized emulsion, indicating that it might have a potential application in the treatment of melanoma.


Assuntos
Antineoplásicos , Portadores de Fármacos , Melanoma/tratamento farmacológico , Nanopartículas/química , Quercetina , Administração Oral , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Cisplatino/química , Cisplatino/farmacologia , Portadores de Fármacos/química , Portadores de Fármacos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Emulsões , Masculino , Melanoma/metabolismo , Melanoma/patologia , Camundongos , Quercetina/química , Quercetina/farmacologia
8.
Drug Dev Ind Pharm ; 42(7): 1165-73, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26571009

RESUMO

The flavonoid quercetin (QU) is a naturally occurring compound with several biological activities. However, the oral bioavailability of this compound is very low due to the high pre-systemic metabolism in the colon and liver and its low water solubility. In this context, the development of QU-loaded nanocarriers (NEs) is a promising approach to improve the drug oral bioavailability. This study investigates the variation of the concentration of 12-hydroxystearic acid-polyethylene glycol copolymer, lecithin and castor oil (CO) as to increase the amount of QU encapsulated while maintaining physicochemical characteristics described in previous studies. To better understand the ability to load and release the drug, we investigated the molecular interactions between QU and NE. Lipid-based NEs were prepared using CO as oily phase and PEG 660-stearate and lecithin as surfactants. Hot solvent diffusion and phase inversion temperature were methods employed to produce NEs. The QU-NEs were investigated for physicochemical characteristics and in vitro drug release. Molecular interactions between QU and the NEs were monitored through the complementary infrared (Fourier transform infrared) and NMR. The results revealed that it was possible to incorporate higher amounts of QU in a lipid-based NE with a reduced size (20 nm). The system developed allow a sustained release of QU probably due to the shell formed by the surfactants around the NE and the flavonoid ordering effect in the emulsion hydrophobic regions, which may reduce the system permeability.


Assuntos
Óleo de Rícino/química , Portadores de Fármacos/química , Lecitinas/química , Nanopartículas/química , Polietilenoglicóis/química , Quercetina/administração & dosagem , Ácidos Esteáricos/química , Composição de Medicamentos , Interações Medicamentosas , Liberação Controlada de Fármacos , Espectroscopia de Ressonância Magnética , Microscopia Eletrônica de Transmissão , Tamanho da Partícula , Quercetina/química , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier , Propriedades de Superfície
9.
Eur J Pharm Sci ; 197: 106766, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38615970

RESUMO

One of the most frequent causes of respiratory infections are viruses. Viruses reaching the airways can be absorbed by the human body through the respiratory mucosa and mainly infect lung cells. Several viral infections are not yet curable, such as coronavirus-2 (SARS-CoV-2). Furthermore, the side effect of synthetic antiviral drugs and reduced efficacy against resistant variants have reinforced the search for alternative and effective treatment options, such as plant-derived antiviral molecules. Curcumin (CUR) and quercetin (QUE) are two natural compounds that have been widely studied for their health benefits, such as antiviral and anti-inflammatory activity. However, poor oral bioavailability limits the clinical applications of these natural compounds. In this work, nanoemulsions (NE) co-encapsulating CUR and QUE designed for nasal administration were developed as promising prophylactic and therapeutic treatments for viral respiratory infections. The NEs were prepared by high-pressure homogenization combined with the phase inversion temperature technique and evaluated for their physical and chemical characteristics. In vitro assays were performed to evaluate the nanoemulsion retention into the porcine nasal mucosa. In addition, the CUR and QUE-loaded NE antiviral activity was tested against a murine ß-COV, namely MHV-3. The results evidenced that CUR and QUE loaded NE had a particle size of 400 nm and retention in the porcine nasal mucosa. The antiviral activity of the NEs showed a percentage of inhibition of around 99 %, indicating that the developed NEs has interesting properties as a therapeutic and prophylactic treatment against viral respiratory infections.


Assuntos
Administração Intranasal , Antivirais , Curcumina , Emulsões , Quercetina , Curcumina/administração & dosagem , Curcumina/farmacologia , Curcumina/química , Quercetina/administração & dosagem , Quercetina/farmacologia , Quercetina/química , Animais , Antivirais/administração & dosagem , Antivirais/farmacologia , Antivirais/química , Camundongos , Nanopartículas/administração & dosagem , Nanopartículas/química , Suínos , Infecções Respiratórias/tratamento farmacológico , Infecções Respiratórias/virologia , Infecções Respiratórias/prevenção & controle , Mucosa Nasal/metabolismo , Mucosa Nasal/efeitos dos fármacos , Mucosa Nasal/virologia , SARS-CoV-2/efeitos dos fármacos , Tratamento Farmacológico da COVID-19 , Humanos
10.
Biomedicines ; 11(12)2023 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-38137569

RESUMO

Curcumin is a highly promising substance for treating burns, owing to its anti-inflammatory, antioxidant, antimicrobial, and wound-healing properties. However, its therapeutic use is restricted due to its hydrophobic nature and low bioavailability. This study was conducted to address these limitations; it developed and tested two types of lipid nanocarriers, namely nanoemulsions (NE-CUR) and nanostructured lipid carriers (NLC-CUR) loaded with curcumin, and aimed to identify the most suitable nanocarrier for skin burn treatment. The study evaluated various parameters, including physicochemical characteristics, stability, encapsulation efficiency, release, skin permeation, retention, cell viability, and antimicrobial activity. The results showed that both nanocarriers showed adequate size (~200 nm), polydispersity index (~0.25), and zeta potential (~>-20 mV). They also showed good encapsulation efficiency (>90%) and remained stable for 120 days at different temperatures. In the release test, NE-CUR and NCL-CUR released 57.14% and 51.64% of curcumin, respectively, in 72 h. NE-CUR demonstrated better cutaneous permeation/retention in intact or scalded skin epidermis and dermis than NLC-CUR. The cell viability test showed no toxicity after treatment with NE-CUR and NLC-CUR up to 125 µg/mL. Regarding microbial activity assays, free curcumin has activity against P. aeruginosa, reducing bacterial growth by 75% in 3 h. NE-CUR inhibited bacterial growth by 65% after 24 h, and the association with gentamicin had favorable results, while NLC-CUR showed a lower inhibition. The results demonstrated that NE-CUR is probably the most promising nanocarrier for treating burns.

11.
Pharmaceutics ; 14(1)2022 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-35057089

RESUMO

The nose-to-brain delivery of neuroprotective natural compounds is an appealing approach for the treatment of neurodegenerative diseases. Nanoemulsions containing curcumin (CUR) and quercetin (QU) were prepared by high-pressure homogenization and characterized physicochemically and structurally. A negative (CQ_NE-), a positive (CQ_NE+), and a gel (CQ_NEgel) formulation were developed. The mean particle size of the CQ_NE- and CQ_NE+ was below 120 nm, while this increased to 240 nm for the CQ_NEgel. The formulations showed high encapsulation efficiency and protected the CUR/QU from biological/chemical degradation. Electron paramagnetic resonance spectroscopy showed that the CUR/QU were located at the interface of the oil phase in the proximity of the surfactant layer. The cytotoxicity studies showed that the formulations containing CUR/QU protected human nasal cells from the toxicity evidenced for blank NEs. No permeation across an in vitro model nasal epithelium was evidenced for CUR/QU, probably due to their poor water-solubility and instability in physiological buffers. However, the nasal cells' drug uptake showed that the total amount of CUR/QU in the cells was related to the NE characteristics (CQ_NE- > CQ_NE+ > CQ_NEgel). The method used allowed the obtainment of nanocarriers of an appropriate size for nasal administration. The treatment of the cells showed the protection of cellular viability, holding promise as an anti-inflammatory treatment able to prevent neurodegenerative diseases.

12.
Pharmaceutics ; 14(12)2022 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-36559219

RESUMO

Achyrocline satureioides (Lam.) DC extract-loaded nanoemulsions have demonstrated potential for wound healing, with promising effects on keratinocyte proliferation. We carried out the first in vivo investigation of the wound healing activity of a hydrogel containing A. satureioides extract-loaded nanoemulsions. We prepared hydrogels by adding the gelling agent (Carbopol® Ultrez) to extract-loaded nanoemulsions (~250 nm in diameter) obtained by spontaneous emulsification. The final flavonoid content in formulation was close to 1 mg/mL, as estimated by ultra-fast liquid chromatography. Permeation/retention studies using porcine ear skin showed that flavonoids reached deeper layers of pig ear skin when it was damaged (up to 3.2 µg/cm² in the dermis), but did not reach the Franz-type diffusion cell receptor fluid. For healing activity, we performed a dorsal wound model using Wistar rats, evaluating the lesion size, anti-inflammatory markers, oxidative damage, and histology. We found that extract-loaded formulations promoted wound healing by increasing angiogenesis by ~20%, reducing inflammation (tumor necrosis factor α) by ~35%, decreasing lipid damage, and improving the re-epithelialization process in lesions. In addition, there was an increase in the number of blood vessels and hair follicles for wounds treated with the formulation compared with the controls. Our findings indicate that the proposed formulation could be promising in the search for better quality healing and tissue reconstruction.

13.
Pharmaceutics ; 14(10)2022 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-36297456

RESUMO

Despite a considerable number of new antibiotics under going clinical trials, treatment of intracellular pathogens still represents a major pharmaceutical challenge. The use of lipid nanocarriers provides several advantages such as protection from compound degradation, increased bioavailability, and controlled and targeted drug release. Wheat germ agglutinin (WGA) is known to have its receptors on the alveolar epithelium and increase phagocytosis. The present study aimed to produce nanostructured lipid carriers with novel glycosylated amphiphilic employed to attach WGA on the surface of the nanocarriers to improve intracellular drug delivery. High-pressure homogenization was employed to prepare the lipid nanocarriers. In vitro, high-content analysis and flow cytometry assay was employed to study the increased uptake by macrophages when the nanocarriers were grafted with WGA. A lipid nanocarrier with surface-functionalized WGA protein (~200 nm, PDI > 0.3) was successfully produced and characterized. The system was loaded with a lipophilic model compound (quercetin; QU), demonstrating the ability to encapsulate a high amount of compound and release it in a controlled manner. The nanocarrier surface functionalization with the WGA protein increased the phagocytosis by macrophages. The system proposed here has characteristics to be further explored to treat intracellular pathogens.

14.
Nanomaterials (Basel) ; 12(7)2022 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-35407191

RESUMO

Curcumin (CUR) and quercetin (QU) are potential compounds for treatment of brain diseases such as neurodegenerative diseases (ND) because of their anti-inflammatory and antioxidant properties. However, low water solubility and poor bioavailability hinder their clinical use. In this context, nanotechnology arises as a strategy to overcome biopharmaceutical issues. In this work, we develop, characterize, compare, and optimize three different omega-3 (ω-3) fatty acids nanoemulsions (NEs) loaded with CUR and QU (negative, cationic, gelling) prepared by two different methods for administration by intranasal route (IN). The results showed that formulations prepared with the two proposed methods exhibited good stability and were able to incorporate a similar amount of CUR and QU. On the other side, differences in size, zeta potential, in vitro release kinetics, and permeation/retention test were observed. Considering the two preparation methods tested, high-pressure homogenization (HPH) shows advantages, and the CQ NE- obtained demonstrated potential for sustained release. Toxicity studies demonstrated that the formulations were not toxic for Caenorhabditis elegans. The developed ω-3 fatty acid NEs have shown a range of interesting properties for the treatment of brain diseases, since they have the potential to increase the nose-to-brain permeation of CUR and QU, enabling enhanced treatments efficiency.

15.
Pharmaceutics ; 13(8)2021 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-34452202

RESUMO

Achyrocline satureioides (Lam.) DC Asteraceae extracts (ASEs) have been investigated for the treatment of various skin disorders. This study reports the effects of ASE-loaded nanoemulsions (NEASE) on the cellular viability, death by necrosis, and migration of immortalized human keratinocytes (HaCaT cell line), as well as the irritant potential through the hen's egg chorioallantoic membrane test (HET-CAM). NEASE exhibited a polydispersity index above 0.12, with a droplet size of 300 nm, ζ-potential of -40 mV, and content of flavonoids close to 1 mg/mL. No cytotoxicity of the ASE was observed on HaCaT by MTT assay (up to 10 µg/mL). A significant increase of HaCaT viability was observed to NEASE (up to 5 µg/mL of flavonoids), compared to treatment with the ASE. The necrosis death evaluation demonstrated that only NEASE did not lead to cell death at all the tested concentrations. The scratch assay demonstrated that NEASE was able to increase the cell migration at low flavonoid concentrations. Finally, the HET-CAM test proved the non-irritative potential of NEASE. Overall, the results indicate the potential of the proposed formulations for topical use in wound healing, in view of their promising effects on proliferation and migration in keratinocytes, combined with an indication of the absence of cytotoxicity and non-irritating potential.

16.
Neurotox Res ; 39(3): 787-799, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33860897

RESUMO

Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor dysfunction. Recent studies have shown that curcumin (CUR) has neuroprotective effects in PD experimental models. However, its efficacy is limited due to low water solubility, bioavailability, and access to the central nervous system. In this study, we compared the effects of new curcumin-loaded nanoemulsions (NC) and free CUR in an experimental model of PD. Adult Swiss mice received NC or CUR (25 and 50 mg/kg) or vehicle orally for 30 days. Starting on the eighth day, they were administered rotenone (1 mg/kg) intraperitoneally until the 30th day. At the end of the treatment, motor assessment was evaluated by open field, pole test, and beam walking tests. Oxidative stress markers and mitochondrial complex I activity were measured in the brain tissue. Both NC and CUR treatment significantly improved motor impairment, reduced lipoperoxidation, modified antioxidant defenses, and prevented inhibition of complex I. However, NC was more effective in preventing motor impairment and inhibition of complex I when compared to CUR in the free form. In conclusion, our results suggest that NC effectively enhances the neuroprotective potential of CUR and is a promising nanomedical application for PD.


Assuntos
Curcumina/administração & dosagem , Emulsões/administração & dosagem , Nanopartículas/administração & dosagem , Fármacos Neuroprotetores/administração & dosagem , Transtornos Parkinsonianos/prevenção & controle , Rotenona/toxicidade , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/química , Curcumina/química , Emulsões/química , Masculino , Camundongos , Nanopartículas/química , Fármacos Neuroprotetores/química , Transtornos Parkinsonianos/induzido quimicamente , Transtornos Parkinsonianos/metabolismo
17.
Curr Drug Deliv ; 18(6): 770-778, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33583376

RESUMO

BACKGROUND: Lipid nanocarriers have been widely tested as drug delivery systems to treat diseases due to their bioavailability, controlled release, and low toxicity. For the pulmonary route, the Food and Drug Administration favors the use of substances generally recognized as safe, as well as biodegradable and biocompatible to minimize the possibility of toxicity. Tuberculosis (TB) remains a public health threat worldwide, mainly due to the long treatment duration and adverse effects. Therefore, new drug delivery systems for treating TB are needed. OBJECTIVE: Physicochemical characterization of different lipid-based nanocarriers was used to optimize carrier properties. Optimized systems were incubated with Mycobacterium tuberculosis to assess whether lipid-based systems act as the energy source for the bacteria, which could be counterproductive to therapy. METHODS: Several excipients and surfactants were evaluated to prepare different types of nanocarriers using high-pressure homogenization. RESULTS: A mixture of trimyristin with castor oil was chosen as the lipid matrix after differential scanning calorimetry analysis. A mixture of egg lecithin and PEG-660 stearate was selected as an optimal surfactant system, as this mixture formed the most stable formulations. Three types of lipid nanocarriers, solid lipid nanoparticles, nanostructured lipid carriers (NLC), and nanoemulsions, were prepared, with the NLC systems showing the most suitable properties for further evaluation. It may provide the advantages of increasing the entrapment efficiency, drug release, and the ability to be lyophilized, producing powder for pulmonary administration as an alternative to entrap poor water-soluble molecules. CONCLUSION: Furthermore, the NLC system can be considered for use as a platform for the treatment of TB through the pulmonary route.


Assuntos
Portadores de Fármacos , Nanopartículas , Tuberculose , Excipientes , Humanos , Lipídeos , Tamanho da Partícula , Tuberculose/tratamento farmacológico
18.
Assay Drug Dev Technol ; 18(7): 298-307, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33054379

RESUMO

Tuberculosis (TB) remains a major global health problem. Conventional treatments fail either because of poor patient compliance with the drug regimen or due to the emergence of multidrug-resistant TB. Thus, not only has the discovery of new compounds and new therapeutic strategies been the focus of many types of research but also new routes of administration. Pulmonary drug delivery possesses many advantages, including the noninvasive route of administration, low metabolic activity, and control environment for systemic absorption, and avoids first-pass metabolism. The use of lipid nanocarriers provides several advantages such as protection of the compound's degradation, increased bioavailability, and controlled drug release. In this study, we review some points related to how the use of lipid nanocarriers can improve TB treatment with inhaled nanomedicines. This review also discusses the current approaches and formulations developed to achieve optimal pulmonary drug delivery systems with nanocarriers targeting alveolar macrophages.


Assuntos
Antituberculosos/uso terapêutico , Lipídeos/química , Nanopartículas/química , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Administração por Inalação , Antituberculosos/administração & dosagem , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Humanos , Macrófagos Alveolares/efeitos dos fármacos , Macrófagos Alveolares/metabolismo , Tuberculose Resistente a Múltiplos Medicamentos/metabolismo
19.
Colloids Surf B Biointerfaces ; 196: 111301, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32871442

RESUMO

Soybean isoflavone aglycones have been investigated as potential wound healing compounds for topical application. The aim of this study was to evaluate the wound healing properties of a soybean isoflavone aglycones-rich fraction (IAF) when incorporated into lipid nanoemulsions dispersed in acrylic-acid hydrogels. Formulations exhibited a mean droplet size in the sub 200 nm range, negative ζ-potential (-60 mV), and displayed non-Newtonian pseudoplastic behavior. The addition of a gelling agent decreased the IAF release from formulations and improved the retention of these compounds in intact porcine ear skin when compared with a control propylene glycol solution. No IAF were detected in receptor fluid of Franz-type diffusion cells. However, increasing amounts of IAF were noticed in both skin layers and the receptor fluid when the tissue was partially injured (tape stripping), or when the epidermis was completely removed. In vitro studies showed that IAF elicits an increased proliferation and migration of keratinocytes (HaCaT cell line). Subsequently, the healing effect of the formulations was evaluated in a model of dorsal wounds in rats, by assessing the size of the lesions, histology, inflammatory markers, and antioxidant activity. Overall findings demonstrated the potential of IAF-loaded formulations to promote wound healing by increasing angiogenesis by ∼200 %, reducing the lipid oxidation (TBARS) by ∼52 % and the inflammation (TNFα) by ∼35 %, while increasing re-epithelialization by ∼500 %, visualized by the epithelium thickness.


Assuntos
Hidrogéis , Isoflavonas , Animais , Isoflavonas/farmacologia , Ratos , Pele , Glycine max , Suínos , Cicatrização
20.
Eur J Pharm Sci ; 148: 105318, 2020 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-32205230

RESUMO

ß-caryophyllene is a sesquiterpene present in the oil of many plant species, such as Copaifera sp., which has been shown to possesses potent anti-inflammatory action; however, its healing activity remains under study. The objectives of the present study were to produce a nanoemulsion containing ß-caryophyllene followed by a hydrogel containing nanoemulsified ß-caryophyllene, to evaluate the permeation profile in vitro, and to assess the in vivo healing activity, which is so far unexplored in the literature for pure ß-caryophyllene and in pharmaceutical formulation. The nanoemulsion was obtained through high-pressure homogenization and the hydrogel by direct dispersion with hydroxyethylcellulose. Both formulations were characterized according to droplet size, polydispersity index, volume-weighted mean diameters, particle distribution, droplets diameters tracking, zeta potential, viscosity and bioadhesion behavior. ß-caryophyllene content was determined by gas chromatography coupled with mass spectrometry (GC/MS). Both formulations presented a nanometric droplet size, negative zeta potential, high ß-caryophyllene content, and were stable for 60 days. In agreement with the viscosity results, the hydrogel containing the ß-caryophyllene nanoemulsion showed superior bioadhesiveness than the nanoemulsion. The skin permeation study in Franz cells demonstrated that isolated ß-caryophyllene was unable to cross the stratum corneum and that its nanoemulsification promoted its permeation. On the other hand, in the simulated deeply wounded skin (dermis), no significant differences were observed between the formulations and isolated ß-caryophyllene with respect to the amount of marker retention in the dermis, suggesting saturation of this skin layer. For the study of healing activity, the dorsal wound model was performed with an evaluation of the lesion size, anti-inflammatory markers, and antioxidant activity. The initial closure of the wound was achieved sooner in the group treated with the hydrogel containing the ß-caryophyllene nanoemulsion, indicating its anti-inflammatory effect. The histological analysis indicated that on day 12 day of the lesion, the hydrogel presented similar results to those of the positive control group (Dersani® oil), proving effectiveness in cutaneous tissue repair.


Assuntos
Sesquiterpenos Policíclicos/farmacologia , Cicatrização/efeitos dos fármacos , Animais , Anti-Inflamatórios/metabolismo , Emulsões/farmacologia , Hidrogéis/farmacologia , Inflamação/metabolismo , Interleucina-1/metabolismo , Masculino , Ratos , Ratos Wistar , Pele/patologia , Absorção Cutânea/efeitos dos fármacos , Suínos , Fator de Necrose Tumoral alfa/metabolismo
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