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Milk-clotting enzyme (MCE) is the essential active agents in dairy processing. The traditional MCE is mainly obtained from animal sources, in which calf rennet is the most widely used in cheese industry. Traditional MCE substitute is becoming necessary due to its limited production and increased cheese consumption. A novel traditional MCE substitute was produced from Bacillus velezensis DB219 in this study. The DB219 MCE exhibited a notable specific activity of 6,110 Soxhlet units/mg and 3.16-fold purification yield with 28.87% recovery through ammonium sulfate fractionation and DEAE-Sepharose Fast Flow. The purified DB219 MCE was a metalloprotease with a molecular weight of 36 kDa. The DB219 MCE was weak acid resistance and stable at pH 6.0 to 10.0 and temperature <45°C. The highest milk-clotting activity was observed in substrate at pH 5.5 added with 20 to 30 mM CaCl2. The Michaelis constant and maximal velocity for casein were 0.31 g/L and 14.22 µmol/min. The DB219 MCE preferred to hydrolyze ß-casein instead of α-casein. The DB219 MCE hydrolyzed α-casein, ß-casein, and κ-casein to generate significantly different peptides in comparison with calf rennet and ES6023 MCE (fungal MCE) through SDS-PAGE and reversed-phase HPLC analysis. The DB219 MCE mainly cleaved Thr124-Ile125 and Ser104-Phe105 bonds in κ-casein and had unique casein cleavage sites and peptide composition through LC-MS/MS analysis. The DB219 MCE was potential to be a new milk coagulant and enriched kinds of traditional MCE substitute.
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Queijo , Leite , Animais , Leite/química , Caseínas/química , Cromatografia Líquida/veterinária , Espectrometria de Massas em Tandem/veterinária , Metaloproteases , Peptídeos/análise , Queijo/análiseRESUMO
Caffeine, which shares consubstantial structural similarity with purine adenosine, has been demonstrated as a nonselective adenosine receptor antagonist for eliciting most of the biological functions at physiologically relevant dosages. Accumulating evidence supports caffeine's beneficial effects against different disorders, such as total cardiovascular diseases and type 2 diabetes. Conversely, paradoxical effects are also linked to caffeine ingestion in humans including hypertension-hypotension and tachycardia-bradycardia. These observations suggest the association of caffeine action with its ingested concentration and/or concurrent interaction with preferential molecular targets to direct explicit events in the human body. Thus, a coherent analysis of the functional targets of caffeine, relevant to normal physiology, and disease pathophysiology, is required to understand the pharmacology of caffeine. This review provides a broad overview of the experimentally validated targets of caffeine, particularly those of therapeutic interest, and the impacts of caffeine on organ-specific physiology and pathophysiology. Overall, the available empirical and epidemiological evidence supports the dose-dependent functional activities of caffeine and advocates for further studies to get insights into the caffeine-induced changes under specific conditions, such as asthma, DNA repair, and cancer, in view of its therapeutic applications.
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Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Hipertensão , Humanos , Cafeína/farmacologia , Cafeína/química , Hipertensão/tratamento farmacológicoRESUMO
CONTEXT: Curcumin (Cur) has a short duration of action which limits its therapeutic efficacy. Carbonic acid 17-(1,5-dimethyl-hexyl)-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl ester 4-[7-(4-hydroxy-3-methoxy-phenyl)-3,5-dioxo-hepta-1,6-dienyl]-2-methoxy-phenyl ester (CUD), as a small molecule derivative of Cur with superior stability, has been developed in our laboratory. OBJECTIVE: CUD-loaded solid lipid nanoparticles (CUD-SLN) were prepared to prolong the duration of the drug action of Cur. MATERIALS AND METHODS: CUD-SLN were prepared with Poloxamer 188 (F68) and hydrogenated soybean phospholipids (HSPC) as carriers, and the prescription was optimized. The in vitro release of CUD and CUD-SLN was investigated. CUD-SLN (5 mg/kg) was injected into Sprague Dawley (SD) rats to investigate its pharmacokinetic behaviour. RESULTS: CUD-SLN features high entrapment efficiency (96.8 ± 0.4%), uniform particle size (113.0 ± 0.8 nm), polydispersity index (PDI) (0.177 ± 0.007) and an appropriate drug loading capacity (6.2 ± 0.1%). Optimized CUD-SLN exhibited sustained release of CUD for about 48 h. Moreover, the results of the pharmacokinetic studies showed that, compared to Cur, CUD-SLN had a considerably prolonged half-life of 14.7 h, slowed its metabolism in vivo by 35.6-fold, and had an improved area under the curve (AUC0-t) of 37.0-fold. CONCLUSIONS: CUD-SLN is a promising preparation for the development of a small molecule derivative of Cur.
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Curcumina , Nanopartículas , Ratos , Animais , Portadores de Fármacos , Ratos Sprague-Dawley , Lipídeos , Sistemas de Liberação de Medicamentos , Tamanho da PartículaRESUMO
Glucosinolate (GSL) is an important active substance in broccoli and can be hydrolyzed to isothiocyanates (ITCs) by endogenous myrosinase. The ITCs are well-known chemopreventive agents that have received significant attention across the nutrition and pharmaceutical industries due to their anticancer properties. Myrosinase activity decreases during the cooking of broccoli, thus it is essential to study the microbiota involved in GSL hydrolysis to maximize their health benefits. In this study, two strains (Enterococcus gallinarum HG001 and Escherichia coli HG002) isolated from the gut microbiota of C57BL/6 mice were identified through 16 S rRNA gene sequence and characteristic analyses. The maximum GSL hydrolysis activity of 12 strains was observed using the cyclocondensation method. Their growth curves, GSL-hydrolysis curves, ITC generation curves and GSL-hydrolysis products were analyzed. The En. gallisepticum HG001 hydrolyzed GSL to a greater level than the E. coli HG002. It was observed that they could hydrolyze GSL to produce erucin nitrile and 4-methylsulfanylbutyro nitrile through gas chromatography-mass spectrometer analysis. Supplementary Information: The online version contains supplementary material available at 10.1007/s12088-022-01006-z.
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A fluorometric immunoassay is described for the determination of patulin, a highly toxic fungal metabolite. A rabbit anti-patulin-bovine serum albumin (BSA) IgG conjugate was prepared and used to compose immunoliposomes and immunomagnetic nanoparticles. The immunomagnetic nanoparticles are then added to the sample to form the patulin-antibody composites which can be magnetically separated. The immunoliposomes are then added to form a sandwich. After magnetic separation of the composites and adding n-octyl-ß-D-glucopyranoside, the fluorophore sulforhodamine B (SRB) is released. Its fluorescence intensity was then measured at excitation/emission wavelengths of 550/585 nm. The immunoliposome-based immunomagnetic nanoparticle assay can detect 8 µg L-1 of patulin in apple juice without the need for extraction, separation, and purification. The detection limit falls within the European regulatory limit for infants and children's products (10 µg L-1). The method is rapid, enviroment-friendly, and reliable. Graphical abstractSchematic of the immunoassay.An immunoliposome-patulin-immunomagnetic nanoparticle sandwich complex is formed that can be separated from the sample by magnetic force. The fluorescence of sulforhodamine B carried inside of immunoliposome was measured to determine patulin. The method can detect 8 µg L-1 of patulin in apple juice.
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Fluorometria , Imunoensaio , Separação Imunomagnética , Nanopartículas/química , Patulina/análise , Animais , Imunoglobulina G/química , Lipossomos/química , Tamanho da Partícula , Coelhos , Soroalbumina Bovina/química , Propriedades de SuperfícieRESUMO
Cronobacter species are foodborne pathogens that can affect the human central nervous system. Survivors of Cronobacter infections often suffer from severe neurological impairments, including hydrocephalus, quadriplegia, and developmental delays in all ages, especially in infants and the immunocompromised. Moreover, Cronobacter species pose a high risk in powdered infant formula (PIF) because PIF is a major source of nutrition for infants worldwide. To develop a rapid and sensitive detection method for Cronobacter species in PIF, immunoliposomes and immunomagnetic nanoparticles were synthesized, after which an immunoliposome-based immunomagnetic concentration and separation assay was developed and applied to PIF for the detection of Cronobacter species. The detection limits of the developed assay were 5.9 × 103 ± 0.7-4.8 × 104 ± 0.2 CFU/mL for Cronobacter species in pure culture with no cross-reactivity with 13 other tested non-Cronobacter strains. Additionally, the developed assay could provide results in 3 h when the contaminated level was higher than 104 CFU/25 g PIF and in 9 h when the contaminated level was 10 CFU/25 g PIF. The developed immunoliposome-based immunomagnetic concentration and separation assay is rapid, sensitive, and simple and thus has great potential for use in the detection of Cronobacter species in PIF.
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Cronobacter/isolamento & purificação , Contaminação de Alimentos/análise , Separação Imunomagnética/métodos , Fórmulas Infantis/microbiologia , Cronobacter/classificação , Cronobacter/genética , Humanos , Separação Imunomagnética/instrumentação , Fórmulas Infantis/análise , Pós/análiseRESUMO
Current trends in the application of nanomaterials are emerging in the nano-biotechnological sector for development of medicines. Cyanobacteria (blue-green algae) are photosynthetic prokaryotes that have applications to human health and numerous biological activities as dietary supplements. Cyanobacteria produce biologically active and chemically diverse compounds such as cyclic peptides, lipopeptides, fatty acid amides, alkaloids, and saccharides. More than 50% of marine cyanobacteria are potentially exploitable for the extraction of bioactive substances, which are effective in killing cancer cells by inducing apoptotic death. The current review emphasizes that not even 10% of microalgal bioactive components have reached commercialized platforms due to difficulties related to solubility. Considering these factors, they should be considered as a potential source of natural products for drug discovery and drug delivery approaches. Nanoformulations employing a wide variety of nanoparticles and their polymerized forms could be an emerging approach to the development of new cancer drugs. This review highlights recent research on microalgae-based medicines or compounds as well as their biomedical applications. This review further discusses the facts, limitations, and commercial market trends related to the use of microalgae for industrial and medicinal purposes.
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Antineoplásicos/uso terapêutico , Fatores Biológicos/uso terapêutico , Cianobactérias/metabolismo , Sistemas de Liberação de Medicamentos/métodos , Microalgas/metabolismo , Neoplasias/tratamento farmacológico , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Fatores Biológicos/química , Fatores Biológicos/isolamento & purificação , Biotecnologia/métodos , Biotecnologia/tendências , Comércio/tendências , Composição de Medicamentos/métodos , Descoberta de Drogas/métodos , Descoberta de Drogas/tendências , Estabilidade de Medicamentos , Humanos , Nanopartículas/química , Nanopartículas/uso terapêutico , Nanotecnologia/métodos , Nanotecnologia/tendências , SolubilidadeRESUMO
Cronobacter spp. are important foodborne pathogens that carry a very high risk of infection to neonates as well as immunocompromised individuals. In the present study, fluorescence-based liposome immunoassay was developed as a new sensitive and rapid diagnostic system for detection of Cronobacter muytjensii (C. muytjensii). Liposomes (size, 206 nm) used in this study were made from cholesterol, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine, 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine, 1,2-dipalmitoyl-sn-glycero-3-[phospho-rac-(1-glycerol)], and sulforhodamine B (SRB). The outer surface of liposome was conjugated with rabbit anti-C. muytjensii IgG in order to develop immunoliposome. The immunoliposome was incubated with C. muytjensii, which was coated on a 96-well plate. Immunoliposomes bound to C. muytjensii were lysed with 30 mM octyl ß-D-glucopyranoside, after which the SRB fluorescence signal was measured at an excitation wavelength of 550 nm and emission wavelength of 585 nm. The signal was directly proportional to the amount of bacterial cells in the test sample. The developed fluorescence-based liposome immunoassay was confirmed to be highly specific to C. muytjensii with a detection limit of 6.3 × 10(4) CFU ml(-1) in pure culture as well as sensitive, efficient, and rapid when compared to culture-based methods. Based on its rapid efficiency and low cost, this fluorescence-based liposome immunoassay may be used to develop diagnostic kits for C. muytjensii detection.
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Cronobacter/classificação , Imunofluorescência , Imunoensaio , Animais , Antígenos de Bactérias/imunologia , Imunoglobulina G/imunologia , Lipossomos , Coelhos , Sensibilidade e EspecificidadeRESUMO
Poor vitamin D status is a widespread problem regardless of age and sex, emphasizing the necessity of new food sources to improve vitamin D levels. Currently, approximately 60% of dietary vitamin D consumption occurs via fortified foods. Vitamin D insufficiency (50-90%) is widespread according to age and region, despite different levels of sunlight exposure. The food industry must identify more effective strategies to increase normal dietary vitamin D intake and improve overall health. Strategies for vitamin D fortification include bioaddition, wherein a vitamin D-rich food source is added to staple foods during processes. These bioadditive strategies expand the range of vitamin D-containing foods and appeal to different preferences, cultures, and economic statuses. In several countries, vitamin D deficiency places athletes at a high risk of disease susceptibility. Due to low sun exposure, athletes in countries with higher and lower levels of sunlight have similar risks of vitamin D deficiency. In this review, we summarize recent technical advances to promote vitamin D utilization by humans during sports activities and in relation to the normal practices of athletes.
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Milk-clotting enzyme (MCE) is a crucial active agent in cheese making. It is necessary to find traditional MCE substitutes due to the limited production of traditional MCE (e.g., calf rennet) and increased cheese consumption. Bacillus megaterium strain LY114 with good milk-clotting activity (MCA) (448 SU/mL) and a high MCA/proteolytic activity (PA) ratio (6.0) was isolated and identified from agricultural soil in Laiyang (Shandong, China) through 16S rRNA sequencing of 45 strains. The Bacillus megaterium LY114 MCE had a remarkable specific activity (7532 SU/mg) and displayed a 4.83-fold purification yield with 34.17% recovery through ammonium sulfate fractionation and DEAE-Sepharose Fast Flow. The purified LY114 MCE was a metalloprotease with a molecular weight of 30 kDa. LY114 MCE was stable at pH 5.0-7.0 and temperature <40 °C. The highest MCA appeared at a substrate pH of 5.5 with 30 mM CaCl2. The Michaelis constant (Km) and maximal velocity (Vm) for casein were 0.31 g/L and 14.16 µmol/min, respectively. LY114 MCE preferred to hydrolyze α-casein (α-CN) rather than ß-casein (ß-CN) and had unique α-CN, ß-CN and κ-casein (κ-CN) cleavage sites. LY114 MCE hydrolyzed casein to generate significantly different peptides compared with calf rennet and fungal MCE as determined by SDS-PAGE analysis. Chemical index analysis and sensory evaluation confirmed the usefulness of LY114 MCE in cheese making. LY114 MCE had the potential to be used in dairy processing and enriched traditional MCE substitutes.
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Bacillus megaterium , Queijo , Caseínas , RNA Ribossômico 16S/genéticaRESUMO
The production of saffron spice results in numerous byproducts, as only 15 g of spice can be produced from 1 kg of flowers, indicating that over 90% of the saffron flower material is eventually discarded as waste. In view of this, the paper reviews current knowledge on the natural active components in saffron byproducts and their biological activities, aiming to lay a theoretical and scientific foundation for the further utilization. Saffron byproducts contain a variety of phytochemical components, such as flavonoids, anthocyanins, carotenoids, phenolic acids, monoterpenoids, alkaloids, glycosides, and saponins. The activities of saffron byproducts and their mechanisms are also discussed in detail here.
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Produtos Biológicos , Crocus , Antocianinas , Extratos Vegetais/farmacologia , Carotenoides , Antioxidantes , Flores , CorantesRESUMO
Vibrio parahaemolyticus is a halophilic and heat-labile gram-negative bacterium and is the most prevalent foodborne bacterium in seafood. In order to develop a rapid and sensitive method for detecting the foodborne pathogenic bacterium Vibrio parahaemolyticus, an aptamer-modified magnetic nanoparticle and an aptamer-modified upconversion nanoparticle were synthesised and used as a capture probe and a signal probe, respectively. The aptamer-modified magnetic nanoparticle, V. parahaemolyticus cell, and aptamer-modified upconversion nanoparticle formed a sandwich-like complex, which was rapidly separated from a complex matrix using a magnetic force, and the bacterial concentration was determined by fluorescence intensity analysis. The results showed that the fluorescence intensity signal correlated positively with the concentration of V. parahaemolyticus in the range of 3.2 × 102 to 3.2 × 105 CFU/mL, with a linear equation of y = 296.40x - 217.67 and a correlation coefficient of R2 = 0.9610. The detection limit of the developed method was 4.4 CFU/mL. There was no cross-reactivity with other tested foodborne pathogens. This method is highly specific and sensitive for the detection of V. parahaemolyticus, and can achieve the qualitative detection of this bacterium in a complex matrix.
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The milk-clotting enzyme (MCE) is a crucial ingredient in cheese manufacture. Due to the limits of traditional MCE, finding viable substitute is a pressing issue. This study aims to isolate and identify a wild strain with high milk-clotting activity (MCA) and low proteolytic activity (PA) and optimize the fermentation conditions for MCE production. A strain of Bacillus velezensis DB219 with high MCA/PA value (9.2) was isolated from dairy soil (Wuchang, Heilongjiang, China) and identified through 16S rRNA from 40 strains. The optimal wheat bran, carbon, nitrogen, inoculum size, volume and initial pH were 60 g/L, soluble starch 12.5 g/L, corn steep liquor 3 g/L, 5%, 40 mL and 6.15, respectively for improving DB219 MCE production through single factor experiment. The wheat bran concentration, corn steep liquor concentration and volume were the most critical factor and their changed range was determined through Plackett-Burman design and the steepest ascent/descent experiments. The response surface analysis experiment of three factors and three levels was conducted by Box-Behnken design. The theoretical optimal fermentation conditions for DB219 MCE were as follows: wheat bran concentration 60.14 g/L, soluble starch 12.5 g/L, corn steep liquor 3 g/L, inoculum size 5%, volume 40.08 mL and initial pH 6.15. DB219 MCE achieved the maximal MCA (3164.84 SU/mL) that was 101.9% of the predicted value (3104.49 SU/mL) and 4.3-fold higher than the control.
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INTRODUCTION: Maturity-onset diabetes of the young (MODY) is an autosomal dominant monogenic diabetes. We report a pair of father and son diagnosed as MODY13 with a new mutation c.685G>A:p.E229K in the inwardly rectifying subfamily J, member 11 (KCNJ11) gene. CASE PRESENTATION: A pair of father and son was examined after admission to the hospital and a whole exome test performed. Whole exome test showed that there was a mutation c.685G>A:p.E229K in the KCNJ11 gene encoding a potassium channel, KCNJ11. CONCLUSIONS: The diagnosis of MODY13 requires genetic testing. After confirmation, medication and diet need to be adjusted to control blood glucose. The treatment plan was adjusted. After glimepiride was administered, symptoms of diabetes were effectively improved. According to our knowledge, this is the first reported mutation of c.685G>A:p.E229K in the KCNJ11 gene.
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Diabetes Mellitus Tipo 2 , Canais de Potássio Corretores do Fluxo de Internalização , Glicemia , Diabetes Mellitus Tipo 2/genética , Humanos , Mutação , Canais de Potássio Corretores do Fluxo de Internalização/genéticaRESUMO
Broccoli extract mainly contains polyphenols and glucosinolates (GSLs). GSLs can be hydrolyzed by gut microorganisms into isothiocyanates (ITCs) and other active substances. These substances have anticancer, anti-inflammatory, antimicrobial, and atherosclerosis-reducing functions. In this study, a high concentration (2000 µmol/L GSLs and 24 µmol/L polyphenols) and a low concentration (83 µmol/L GSLs and 1 µmol/L polyphenols) of broccoli extract were prepared. Gut microorganisms from fresh human feces were cultured to simulate the gut environment in vitro. The GSL content decreased and the types and content of ITCs increased with broccoli extract hydrolysis through cyclic condensation and gas chromatography-mass spectrometry (GC-MS) analyses. Broccoli extract significantly increased probiotics and inhibited harmful bacteria through 16S rDNA sequencing. Based on phylum level analysis, Firmicutes and Lachnospiraceae increased significantly (P < 0.05). At the genus level, both high- and low-concentration groups significantly inhibited Escherichia and increased Bilophila and Alistipes (P < 0.05). The high-concentration group significantly increased Bifidobacterium (P < 0.05). The broccoli extract improved the richness of gut microorganisms and regulated their structure. The GSL hydrolysis was significantly correlated with Bilophila, Lachnospiraceae, Alistipes, Bifidobacterium, Escherichia, and Streptococcus (P < 0.05). These study findings provide a theoretical foundation for further exploring a probiotic mechanism of broccoli extract in the intestine.
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The first asymmetric meiotic cell divisions in mouse oocytes are driven by formin 2 (FMN2)-nucleated actin polymerization around the spindle. In this study, we investigated how FMN2 is recruited to the spindle peripheral ER and how its activity is regulated in mouse meiosis I (MI) oocytes. We show that this process is regulated by the Ran GTPase, a conserved mediator of chromatin signal, and the ER-associated protein VAPA. FMN2 contains a nuclear localization sequence (NLS) within a domain (SLD) previously shown to be required for FMN2 localization to the spindle periphery. FMN2 NLS is bound to the importin α1/ß complex, and the disruption of this interaction by RanGTP is required for FMN2 accumulation in the area proximal to the chromatin and the MI spindle. The importin-free FMN2 is then recruited to the surface of ER around the spindle through the binding of the SLD with the ER-membrane protein VAPA. We further show that FMN2 is autoinhibited through an intramolecular interaction between the SLD with the C-terminal formin homology 2 (FH2) domain that nucleates actin filaments. VAPA binding to SLD relieves the autoinhibition of FMN2, leading to localized actin polymerization. This dual control of formin-mediated actin assembly allows actin polymerization to initiate the movement of the meiotic spindle toward the cortex, an essential step in the maturation of the mammalian female gamete.
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Actinas , Cromatina , Actinas/metabolismo , Animais , Cromatina/metabolismo , Feminino , Forminas , GTP Fosfo-Hidrolases/metabolismo , Guanosina Trifosfato/metabolismo , Mamíferos , Meiose , Proteínas de Membrana/metabolismo , Camundongos , Proteínas do Tecido Nervoso/metabolismo , Oócitos/fisiologia , Fuso Acromático/metabolismoRESUMO
Brassica vegetables, especially broccoli, have health benefits such as anticancer activity, which are attributed to isothiocyanate (ITC), products of glucosinolate hydrolysis. This study aimed to explore the effect of cooking time and addition of exogenous myrosinase (MYR) from moringa seeds on the yield of ITCs. The results showed that raw broccoli produced a significantly high amount of ITCs, which decreased by almost 40% after microwaving the broccoli for 1 min. Introducing exogenous MYR by adding ground moringa seeds to cooked broccoli caused a notable increase in ITC of 38%. At pH 4.0-6.0, MYR showed optimal activity, and the thermal stability of MYR from moringa seeds was better than that from broccoli. The kinetic parameters indicated that MYR from moringa seeds had a higher affinity to sinigrin than that from broccoli seeds. This study was novel in reporting that adding ground moringa seeds to cooked broccoli enhanced ITC formation.
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Brassica , Moringa , Culinária , Suplementos Nutricionais , Glucosinolatos/análise , Glicosídeo Hidrolases , IsotiocianatosRESUMO
This study investigated the effect of structural modification of Curcumin (CU) combined with the solid lipid nanoparticles (SLN) drug delivery system on anti-tumor activity in vitro. A new structure of Curcumin derivative (CU1) was successfully synthesized by modifying the phenolic hydroxyl group of CU. CU1 was two times more stable than CU at 45 °C or constant light. The SLN containing CU1 (CU1-SLN) was prepared, and the particle size, polydispersity index, entrapment efficiency, drug loading, and zeta potential of CU1-SLN were (104.1 ± 2.43) nm, 0.22 ± 0.008, (95.1 ± 0.38) %, (4.28 ± 0.02) %, and (28.3 ± 1.60) mV, respectively. X-ray diffraction (XRD) and Differential scanning calorimetry (DSC) showed that CU1 is amorphous in SLN. CU1-SLN released the drug slowly for 48 h, while CU and CU1 were released rapidly within 8 h. In terms of cytotoxicity, CU1 exhibited a 1.5-fold higher inhibition than CU against A549 and SMMC-7721 cells, while CU1-SLN showed 2-fold higher inhibition than CU1. Both CU1 and CU1-SLN reduced the toxicity in normal hepatocytes compared with CU (2.6-fold and 12.9-fold, respectively). CU1-SLN showed a significant apoptotic effect (p < 0.05). In summary, CU1 retained the inhibitory effect of CU against tumor cells, while improving stability and safety. Additionally, CU1-SLN presents a promising strategy for the treatment of liver and lung cancer.
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Antineoplásicos , Curcumina , Nanopartículas , Antineoplásicos/química , Antineoplásicos/farmacologia , Curcumina/química , Curcumina/farmacologia , Portadores de Fármacos/química , Lipídeos/química , Lipossomos , Nanopartículas/química , Tamanho da PartículaRESUMO
The main aim of this study was to improve the therapeutic potential of a paclitaxel (PTX) and curcumin (CU) combination regimen using solid lipid nanoparticles (SLNs). PTX and CU were successfully co-encapsulated at a predetermined ratio in SLNs (PC-SLNs) with high encapsulation efficiency (CU: 97.6%, PTX: 95.8%), appropriate particle size (121.8 ± 1.69 nm), small PDI (0.267 ± 0.023), and negative zeta potential (-30.4 ± 1.25 mV). Compared with PTX or the combination of CU and PTX (CU + PTX), PC-SLNs can greatly reduce the dose of PTX while still achieving the same therapeutic effect on four cancer cell lines, among which the inhibitory effect on A549 lung cancer cells was the strongest. PC-SLNs improved the area under the curve (CU: 1.40-fold; PTX: 2.88-fold), prolonged the residence time (CU: 6.94-fold; PTX: 2.51-fold), and increased the half-life (CU: 5.62-fold; PTX: 6.46-fold), achieving long circulation. PC-SLNs were used to treat lung cancer in a nude mouse xenograft tumor model and the tumor suppression rate reached 78.42%, while those of PTX and (CU + PTX) were 40.53% and 51.56%, respectively. As PC-SLNs can prevent P-glycoprotein efflux, reverse MDR and downregulate the NF-κB pathway. PC-SLNs are a potential antineoplastic agent that is more effective and less toxic in treating lung cancer.
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Curcumina , Neoplasias Pulmonares , Nanopartículas , Animais , Humanos , Camundongos , Linhagem Celular Tumoral , Curcumina/farmacologia , Curcumina/uso terapêutico , Lipossomos , Neoplasias Pulmonares/metabolismo , Paclitaxel/farmacologia , Paclitaxel/uso terapêuticoRESUMO
Purpose: Paclitaxel (PTX) has been widely utilized for the treatment of breast cancer. However, drawbacks, such as poor aqueous solubility, rapid blood clearance and severe toxicity, greatly reduce its efficacy and safety. Herein, a novel self-developed curcumin derivative (CUD) was chosen as the carrier to develop a long-acting PTX nano-delivery system (PTX-Sln@CUD) in order to improve its pharmacokinetic behavior, anti-breast cancer efficacy and safety. Methods: PTX-Sln@CUD was prepared using solid dispersion and ultrasonic technology. Relevant physical and chemical properties, including stability and release behavior, were characterized. The clearance of PTX-Sln@CUD in vivo was studied by pharmacokinetic experiments. The anti-tumor activity of PTX-Sln@CUD was investigated in vitro and in vivo. Hemolysis experiments, acute toxicity and cumulative toxicity studies were performed in mice to determine the safety of PTX-Sln@CUD. Results: The average particle size, PDI, Zeta potential, encapsulation efficiency and loading efficiency of the PTX-Sln@CUD were 238.5 ± 4.79 nm, 0.225 ± 0.011, -33.8 ± 1.26 mV, 94.20 ± 0.49% and 10.98 ± 0.31%, respectively. PTX-Sln@CUD was found to be stable at room temperature for half a year. The cumulative release rates of PTX-Sln@CUD at 24, 96 and 168 h were 17.98 ± 2.60, 57.09 ± 2.32 and 72.66 ± 4.16%, respectively, which were adherent to zero-order kinetics. T1/2, MRT (0-t) and AUC (0-t) of the PTX-Sln@CUD group were 4.03-fold (44.293 h), 7.78-fold (38.444 h) and 6.18-fold (14.716 mg/L*h) of the PTX group, respectively. PTX-Sln@CUD group demonstrated stronger anti-breast cancer activity than the PTX group. Importantly, the PTX-Sln@CUD group was safer compared to the PTX group both in vitro and in vivo. Conclusion: PTX-Sln@CUD was verified as promising therapeutic nanoparticles for breast cancer and provided a novel strategy to solve the problem of low efficacy and poor safety of clinical chemotherapy drugs.