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1.
Drug Deliv ; 29(1): 2883-2896, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36062523

RESUMO

The physicochemical properties of "smart" or stimuli-sensitive amphiphilic copolymers can be modeled as a function of their environment. In special, pH-sensitive copolymers have practical applications in the biomedical field as drug delivery systems. Interactions between the structural units of any polymer-drug system imply mutual constraints at various scale resolutions and the nonlinearity is accepted as one of the most fundamental properties. The release kinetics, as a function of pH, of a model active principle, i.e., Curcumin, from nanomicelles obtained from amphiphilic pH-sensitive poly(2-vinylpyridine)-b-poly(ethylene oxide) (P2VP-b-PEO) tailor-made diblock copolymers was firstly studied by using the Rietger-Peppas equation. The value of the exponential coefficient, n, is around 0.5, generally suggesting a diffusion process, slightly disturbed in some cases. Moreover, the evaluation of the polymer-drug system's nonstationary dynamics was caried out through harmonic mapping from the usual space to the hyperbolic one. The kinetic model we developed, based on fractal theory, fits very well with the experimental data obtained for the release of Curcumin from the amphiphilic copolymer micelles in which it was encapsulated. This model is a variant of the classical kinetic models based on the formal kinetics of the process.


Assuntos
Curcumina , Fractais , Micelas , Polietilenoglicóis/química , Polímeros/química
2.
J Nanobiotechnology ; 20(1): 402, 2022 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-36064403

RESUMO

BACKGROUND: 7-p-trifluoromethylphenyl-FL118 (FLQY2) is a camptothecin analog with excellent antitumor efficacy against various solid tumors. However, its poor solubility and low bioavailability limited the development of the drug. Polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (Soluplus®), an emerging carrier for preparing solid dispersion (SD), encapsulated FLQY2 to circumvent the above limitations. RESULTS: In this project, FLQY2-SD was prepared by solvent evaporation method and self-assembled into micelles in aqueous solutions owing to the amphiphilic nature of Soluplus®. The physicochemical characterizations demonstrated that FLQY2 existed in a homogeneous amorphous form in SD and was rapidly dissolved. The micelles did not affect cytotoxicity or cellular uptake of FLQY2 in vitro, and the oral bioavailability was increased by 12.3-fold compared to the FLQY2 cyclodextrin suspension. The pharmacokinetics of FLQY2-SD showed rapid absorption, accumulation in the intestine, and slow elimination via fecal. Metabolite identification studies showed 14 novel metabolites were identified, including 12 phase I metabolites (M1-M12) and 2 phase II metabolites (M13-M14), of which M2 (oxidation after decarboxylation) and M7 (dioxolane ring cleavage) were the primary metabolites in the positive mode and negative mode, respectively. The tumor growth inhibition rate (TGI, 81.1%) of FLQY2-SD (1.5 mpk, p.o./QW) in tumor-bearing mice after oral administration was higher than that of albumin-bound Paclitaxel (15 mpk, i.v./Q4D) and Irinotecan hydrochloride (100 mpk, i.p./QW). CONCLUSIONS: The successful preparation, pharmacokinetics, and pharmacodynamics studies of FLQY2-SD showed that the solubility and bioavailability of FLQY2 were improved, which facilitated the further druggability development of FLQY2.


Assuntos
Excipientes , Micelas , Animais , Disponibilidade Biológica , Camptotecina/farmacologia , Excipientes/química , Camundongos , Solubilidade
3.
J Chem Phys ; 157(9): 094706, 2022 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-36075730

RESUMO

The present work attempts to systematically explore the surfactant sorption at liquid-liquid interfaces with coarse-grained models targeting thermodynamic properties of reference liquid solutions. We employ dissipative particle dynamics with soft-core forcefield tested against experimental data on micellization of surfactants in water, and the previous results are reproduced in this work. We consider three different nonionic surfactants: hexaethylene glycol monododecyl ether (C12E6), 2-[4-(2,4,4-trimethylpentan-2-yl)phenoxy]ethanol) known as Triton X-100 (TX-100), and two alkyl glucoside surfactants (CnG1) with n-alkane tail fragments and a saccharide hydrophilic head at decane-water and toluene-water interfaces. For TX-100, we composed a model based on the literature forcefield and found good agreement with the experimental critical micelle concentrations (CMCs). The head-head interactions are of different origins for different surfactant groups: entropic repulsion between ethylene oxide chains of C12E6 and TX-100, and more chemically specific and complex interactions between the maltose heads of alkyl glucosides. We interpret our results with the Redlich-Peterson equation of monolayer adsorption in order to relate the adsorption to the bulk concentration of the surfactant and the interfacial tension. The densities of the adsorbed monolayer at CMC mostly agree with the experimental data, and a reasonable agreement was obtained for the interfacial tension at CMC. At the same time, we found significant discrepancies between the simulated and experimental adsorption isotherms. We explain them by the oversimplified forcefield: when the parameters are fitted to the free energies of bulk solutions, they may not correctly reproduce the interfacial free energies.


Assuntos
Micelas , Tensoativos , Adsorção , Tensão Superficial , Tensoativos/química , Água/química
4.
Molecules ; 27(17)2022 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-36080376

RESUMO

Reducing the use of solvents is an important aim of green chemistry. Using micelles self-assembled from amphiphilic molecules dispersed in water (considered a green solvent) has facilitated reactions of organic compounds. When performing reactions in micelles, the hydrophobic effect can considerably accelerate apparent reaction rates, as well as enhance selectivity. Here, we review micellar reaction media and their potential role in sustainable chemical production. The focus of this review is applications of engineered amphiphilic systems for reactions (surface-active ionic liquids, designer surfactants, and block copolymers) as reaction media. Micelles are a versatile platform for performing a large array of organic chemistries using water as the bulk solvent. Building on this foundation, synthetic sequences combining several reaction steps in one pot have been developed. Telescoping multiple reactions can reduce solvent waste by limiting the volume of solvents, as well as eliminating purification processes. Thus, in particular, we review recent advances in "one-pot" multistep reactions achieved using micellar reaction media with potential applications in medicinal chemistry and agrochemistry. Photocatalyzed reactions in micellar reaction media are also discussed. In addition to the use of micelles, we emphasize the process (steps to isolate the product and reuse the catalyst).


Assuntos
Micelas , Polímeros , Interações Hidrofóbicas e Hidrofílicas , Polímeros/química , Solventes , Água/química
5.
Int J Mol Sci ; 23(17)2022 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-36077102

RESUMO

To endow the polymeric prodrug with smart properties through a safe and simple method, matrix metalloproteinase (MMPs) responsive peptide GPLGVRGDG was introduced into the block copolymer to prepare TPGS3350-GPLGVRGDG-DOX&DOX micelles, where TPGS3350 is D-α-tocopheryl polyethylene glycol 3350 succinate. During the doxorubicin delivery, the cleavage of the peptide chain triggers de-PEGylation, and the remaining VRGDG sequence was retained on the surface of the micelles, which can act as a ligand to facilitate cell uptake. Moreover, the cytotoxicity of TPGS3350-GPLGVRGDG-DOX&DOX micelles against 4T1 cells was significantly improved, compared with TPGS3350-GPLGVRG-DOX&DOX micelles and TPGS3350-DOX&DOX micelles. During in vivo studies, TPGS3350-GPLGVRGDG-DOX&DOX micelles exhibited good anticancer efficacy with long circulation in the body and more efficient accumulation at the tumor site. Therefore, TPGS3350-GPLGVRGDG-DOX&DOX micelles have improved antitumor activity and reduced toxic side effects. This work opens new potential for exploring the strategy of drug delivery in clinical applications.


Assuntos
Micelas , Polietilenoglicóis , Linhagem Celular Tumoral , Doxorrubicina/química , Doxorrubicina/farmacologia , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Peptídeos/química , Polietilenoglicóis/química , Polímeros
6.
J Dairy Sci ; 105(10): 7891-7903, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36055836

RESUMO

The amount of intact casein provided by dairy ingredients is a critical parameter in dairy-based imitation mozzarella cheese (IMC) formulation because it has a significant effect on unmelted textural parameters such as hardness. From a functionality perspective, rennet casein (RCN) is the preferred ingredient. Milk protein concentrate (MPC) and micellar casein concentrate (MCC) cannot provide the required functionality due to the higher steric stability of casein micelle. However, the use of transglutaminase (TGase) has the potential to modify the surface properties of MPC and MCC and may improve their functionality in IMC. The objective of this study was to determine the effect of TGase-treated MPC and MCC powders on the unmelted textural properties of IMC and compare them with IMC made using commercially available RCN. Additionally, we studied the degree of crosslinking by TGase in MPC and MCC retentates using capillary gel electrophoresis. Three lots of MCC and MPC retentate were produced from pasteurized skim milk via microfiltration and ultrafiltration, respectively, and randomly assigned to 1 of 3 treatments: no TGase (control); low TGase: 0.3 units/g of protein; and high TGase: 3.0 units/g of protein, followed by inactivation of enzyme (72°C for 10 min), and spray drying. Each MCC, MPC, and RCN was then used to formulate IMC that was standardized to 21% fat, 1% salt, 48% moisture, and 20% protein. The IMC were manufactured by blending, mixing, and heating ingredients (4.0 kg) in a twin-screw cooker. The capillary gel electrophoresis analysis showed extensive inter- and intramolecular crosslinking. The IMC formulation using the highest TGase level in MCC or MPC did not form an emulsion because of extensive crosslinking. In MPC with a high level of TGase, whey protein and casein crosslinking were observed. In contrast, crosslinking and hydrolysis of proteins were observed in MCC. The IMC made from MCC powder had significantly higher texture profile analysis hardness compared with the corresponding MPC powder. Further, many-to-one (multiple) comparisons using the Dunnett test showed no significant differences between IMC made using RCN and treatment powders in hardness. Our results demonstrated that TGase treatment causes crosslinking hydrolysis of MCC and MPC at higher TGase levels, and MPC and MCC have the potential to be used as ingredients in IMC applications.


Assuntos
Caseínas , Queijo , Animais , Caseínas/análise , Queijo/análise , Emulsões , Manipulação de Alimentos/métodos , Comportamento Imitativo , Micelas , Proteínas do Leite/análise , Pós , Transglutaminases , Proteínas do Soro do Leite/análise
7.
J Dairy Sci ; 105(10): 7904-7916, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36055846

RESUMO

Melt and stretch properties in dairy-based imitation mozzarella cheese (IMC) are affected by the amount of intact casein provided by dairy ingredients in the formulation. Rennet casein (RCN) is the preferred ingredient to provide intact casein in a formulation. Ingredients produced using membrane technology, such as milk protein concentrate (MPC) and micellar casein concentrate (MCC), are unable to provide the required functionality. However, the use of transglutaminase (TGase) has potential to modify the physical properties of MPC or MCC and may improve their functionality in IMC. The objective of this study was to determine the effect of TGase-treated MPC and MCC retentates on melt and stretch properties when they are used in IMC and to compare them with IMC made using RCN. The MCC and MPC retentates were produced using 3 different lots of pasteurized skim milk and treated with 3 levels of TGase enzyme: no TGase (control), low TGase: 0.3 units/g of protein, and high TGase: 3.0 units/g of protein. Each of the MCC and MPC treatments was heated to 72°C for 10 min to inactivate TGase and then spray dried. Each MCC, MPC, and RCN powder was then used in an IMC formulation that was standardized to 48% moisture, 21% fat, 20% protein, and 1% salt. The IMC were manufactured in a twin-screw cooker by blending, mixing, and heating various ingredients (4.0 kg). Due to extensive crosslinking, the IMC formulation with the highest TGase level (MCC or MPC) did not form an emulsion. The IMC made from MCC treatments had significantly higher stretchability on pizza compared with their respective MPC treatments. The IMC made from TGase-treated MCC and MPC had significantly lower melt area and significantly higher transition temperature (TT) and stretchability compared with their respective controls. Comparison of IMC made using TGase-treated MCC and MPC to the RCN IMC indicated no difference in TT or texture profile analysis-stretchability; however, the Schreiber melt test area was significantly lower. Our results demonstrated that TGase treatment modifies the melt and stretch characteristics of MCC and MPC in IMC applications, and TGase-treated MPC and MCC can be used to replace RCN in IMC formulations.


Assuntos
Queijo , Animais , Caseínas , Queijo/análise , Emulsões , Manipulação de Alimentos/métodos , Comportamento Imitativo , Micelas , Proteínas do Leite/metabolismo , Pós , Transglutaminases
8.
Sci Rep ; 12(1): 15253, 2022 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-36085349

RESUMO

Basket clam soup, a popular Asian dish, is prepared by boiling clams in hot water. The soup is generally cloudy, and it is considered that increased cloudiness enhances taste. However, the composition of the whitening ingredients and their association with taste enhancement remains unclear. In this study, we aimed to identify the components contributing to the white colour of the boiled soup. The white component upon precipitation with trichloroacetic acid reacted positively with ninhydrin, indicating the presence of proteins. The separation of proteins using sodium dodecyl sulphate-polyacrylamide gel electrophoresis revealed an intense band of size 33 kDa. Peptide mass fingerprinting of the identified protein using matrix-assisted laser desorption/ionisation-time-of-flight tandem mass spectrometry revealed the protein as tropomyosin. To validate the involvement of tropomyosin in the turbidity of the soup, tropomyosin was expressed and extracted from Escherichia coli. As expected, the purified protein suspended in water resulted in turbid appearance. To determine whether lipids have any association with the observed cloudiness of the soup, the amounts of fatty acids were measured. The proportion of estimated fatty acids was very low compared to that of proteins. Overall, we identified the major component contributing to soup cloudiness as tropomyosin forming micelles.


Assuntos
Furunculose , Tropomiosina , Animais , Cor , Escherichia coli , Ácidos Graxos , Micelas , Alimentos Marinhos , Frutos do Mar , Água
9.
Int J Nanomedicine ; 17: 4009-4022, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36105622

RESUMO

Background: The poor skin permeation and deposition of topical therapeutic drugs is a major issue in topical drug delivery, improving this issue is conducive to improving the topical therapeutic effect of drugs. Methods: In this study, octadecylamine modified hyaluronic acid (OHA) copolymer was synthesized by amide reaction technique to prepare curcumin (CUR)-loaded micelles (CUR-M) for topical transdermal administration. CUR-M was successfully prepared by dialysis, and the formulation was evaluated for particle size, zeta potential, surface morphology, entrapment effciency (EE%), drug loading (DL), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR) and the in vitro drug release. Additionally, in vitro skin permeation and retention, in vivo topical analgesic and anti-inflammatory activity, and skin irritation were assessed. Results: The mean drug loading (DL), drug entrapment efficiency (EE), hydrodynamic diameter and zeta potential of CUR-M were 8.26%, 90.86%, 165.64 nm and -26.85 mV, respectively. CUR-M was characterized by X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR), it was found that there was an interaction between CUR and OHA, and CUR existed in CUR-M in an amorphous form. CUR-M exhibited sustained release in 48 h and good stability at 4 °C for 21days. CUR-M could significantly increase the skin penetration and retention of CUR and had better analgesic and anti-inflammatory activities in vivo when compared with CUR solution. Hematoxylin-eosin staining results revealed that the transdermal penetration mechanism of CUR-M might be related to the hydration of stratum corneum by HA. In addition, CUR-M showed no skin irritation to mouse skin. Conclusion: CUR-M might be a promising and safe drug delivery system for the treatment of topical diseases.


Assuntos
Curcumina , Micelas , Animais , Sistemas de Liberação de Medicamentos/métodos , Ácido Hialurônico , Camundongos , Diálise Renal
10.
Molecules ; 27(16)2022 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-36014471

RESUMO

Bile salts are a category of natural chiral surfactants which have ever been used as the surfactant and chiral selector for the separation of many chiral compounds by micellar electrokinetic chromatography (MEKC). In our previous works, the application of sodium cholate (SC) in the separation of four stereoisomers of palonosetron (PALO) by MEKC has been studied systematically. In this work, the parameters of other bile salts, including sodium taurocholate (STC), sodium deoxycholate (SDC), and sodium taurodeoxycholate (STDC) in the separation of PALO stereoisomers by MEKC were measured and compared with SC. It was found that all of four bile salts provide chiral recognition for both pairs of enantiomers, as well as achiral selectivity for diastereomers of different degrees. The structure of steroidal ring of bile salts has a greater impact on the separation than the structure of the side chain. The varying separation results by different bile salts were elucidated based on the measured parameters. A model to describe the contributions of the mobility difference of solutes in the aqueous phase and the selectivity of micelles to the chiral and achiral separation of stereoisomers was introduced. Additionally, a new approach to measure the mobility of micelles without enough solubility for hydrophobic markers was proposed, which is necessary for the calculation of separation parameters in MEKC. Under the guidance of derived equations, the separation by SDC and STDC was significantly improved by using lower surfactant concentrations. The complete separation of four stereoisomers was achieved in less than 3.5 min by using 4.0 mM of SDC. In addition, 30.0 mM of STC also provided the complete resolution of four stereoisomers due to the balance of different separation mechanisms. Its applicability for the analysis of a small amount of enantiomeric impurities in the presence of a high concentration of the effective ingredient was validated by a real sample.


Assuntos
Cromatografia Capilar Eletrocinética Micelar , Micelas , Ácidos e Sais Biliares , Cromatografia/métodos , Cromatografia Capilar Eletrocinética Micelar/métodos , Ácido Desoxicólico , Palonossetrom , Colato de Sódio/química , Estereoisomerismo , Tensoativos/química
11.
Int J Nanomedicine ; 17: 3655-3670, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35999993

RESUMO

Purpose: We designed a novel isoliquiritigenin (ISL) loaded micelle prepared with DSPE-PEG2000 as the drug carrier modified with the brain-targeting polypeptide angiopep-2 to improve the poor water solubility and low bioavailability of ISL for the treatment of acute ischemic stroke. Methods: Thin film evaporation was used to synthesize the ISL micelles (ISL-M) modified with angiopep-2 as the brain targeted ligands. The morphology of the micelles was observed by the TEM. The particle size and zeta potential were measured via the nanometer particle size analyzer. The drug loading, encapsulation and in vitro release rates of micelles were detected by the HPLC. The UPLC-ESI-MS/MS methods were used to measure the ISL concentrations of ISL in plasma and main tissues after intravenous administration, and compared the pharmacokinetics and tissue distributions between ISL and ISL-M. In the MCAO mice model, the protective effects of ISL and ISL-M were confirmed via the behavioral and molecular biology experiments. Results: The results showed that the drug loading of ISL-M was 7.63 ± 2.62%, the encapsulation efficiency was 68.17 ± 6.23%, the particle size was 40.87 ± 4.82 nm, and the zeta potential was -34.23 ± 3.35 mV. The in vitro release experiments showed that ISL-M had good sustained-release effect and pH sensitivity. Compared with ISL monomers, the ISL-M could significantly prolong the in vivo circulation time of ISL and enhance the accumulation in the brain tissues. The ISL-M could ameliorate the brain injury induced by the MCAO mice via inhibition of cellular autophagy and neuronal apoptosis. There were no the cellular structural damages and other adverse effects for ISL-M on the main tissues and organs. Conclusion: The ISL-M could serve as a promising and ideal drug candidate for the clinical application of ISL in the treatment of acute ischemic stroke.


Assuntos
AVC Isquêmico , Nanopartículas , Animais , Encéfalo , Chalconas , Camundongos , Micelas , Nanopartículas/química , Espectrometria de Massas em Tandem , Distribuição Tecidual
12.
Methods Enzymol ; 674: 297-327, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36008010

RESUMO

Ongoing efforts to improve the nutritional content of carotenoids in food sources to solve global health problems must also consider bioaccessibility and bioavailability of carotenoids. Carotenoid bioaccessibility encompasses carotenoid release from the food matrix, solubilization in lipid emulsion droplets, and transfer to mixed micelles for further absorption into the intestine. Bioavailability refers to the fraction of carotenoids which enters into circulation. To understand the mechanisms controlling bioaccessibility, in vitro digestion methods have been developed and are a useful approach to overcome some of the disadvantages associated with in vivo protocols. The INFOGEST protocol comprises three phases (oral, gastric and intestinal) to simulate adult human digestion of foods, as an international consensus for the conditions of static in vitro digestion. The last steps in any digestion protocol involve isolation of the target food compounds and subsequent analysis, steps not included in the INFOGEST protocol because they may differ depending on specific physical-chemical characteristics and quantification analysis of the target analyte. In this chapter, we describe the INFOGEST protocol which has been adapted for the analysis of carotenoid bioaccessibility, including determination and calculation of enzyme activities according to INFOGEST guidelines, removal of undigested material, collection of mixed micelles containing carotenoids, extraction, storage and subsequent identification and quantification by liquid chromatography analysis of both free and acylated carotenoids.


Assuntos
Carotenoides , Micelas , Disponibilidade Biológica , Carotenoides/metabolismo , Digestão , Humanos , Técnicas In Vitro
13.
Methods Enzymol ; 674: 329-341, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36008011

RESUMO

Carotenoids are lipophilic isoprenoids with roles in photosynthesis and signaling. Dietary carotenoids are nutritionally relevant as precursors of retinoids (including vitamin A). These pigments also provide health benefits as anti-oxidative, anti-inflammatory or anti-tumor agents, among other biological functions. Such health-related advantages have spurred a strong interest in the biofortification of food products with carotenoids. Most biotechnological approaches have been carried out in plants because dietary carotenoids are primarily obtained from fruits and vegetables. Successful examples abound in the literature but in most cases a critical aspect is neglected: bioaccessibility. A higher content of carotenoids in a given plant product does not necessarily mean an improved dietary intake because these lipophilic compounds must be released from the food and incorporated into intestinal micelles to reach the sites of action in the human body. Bioaccessibility refers to the percentage of the carotenoid that is released from the food matrix during digestion and incorporated into micelles in the gastrointestinal tract. Bioaccessibility substantially changes depending on the physicochemical context and subcellular environment where carotenoids accumulate within plant cells. Here, we present a fast, simplified, inexpensive and efficient in vitro method to estimate bioaccessibility that has been adapted to the requirements and equipment of typical plant molecular biology labs. The availability of this protocol should improve biotechnological efforts aimed at carotenoid biofortification by complementing compositional improvements with bioaccessibility data to better estimate the nutritional value of the newly generated functional food.


Assuntos
Carotenoides , Micelas , Disponibilidade Biológica , Carotenoides/metabolismo , Digestão , Frutas/metabolismo , Humanos
14.
Int J Mol Sci ; 23(16)2022 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-36012646

RESUMO

Glaucoma is the second leading cause of blindness in the world. Despite the fact that many treatments are currently available for eye diseases, the key issue that arises is the administration of drugs for long periods of time and the increased risk of inflammation, but also the high cost of eye surgery. Consequently, numerous daily administrations are required, which reduce patient compliance, and even in these conditions, the treatment of eye disease is too ineffective. Micellar polymers are core-shell nanoparticles formed by the self-assembly of block or graft copolymers in selective solvents. In the present study, polymeric micelles (PMs) were obtained by dialysis from smart biocompatible poly(ε-caprolactone)-poly(N-vinylcaprolactam-co-N-vinylpyrrolidone) [PCL-g-P(NVCL-co-NVP)] graft copolymers. Two copolymers with different molar masses were studied, and a good correlation was noted between the micellar sizes and the total degree of polymerisation (DPn) of the copolymers. The micelles formed by Cop A [PCL120-g-P(NVCL507-co-NVP128)], with the lowest total DPn, have a Z-average value of 39 nm, whereas the micellar sizes for Cop B [PCL120-g-P(NVCL1253-co-NVP139)] are around 47 nm. These PMs were further used for the encapsulation of two drugs with applications for the treatment of eye diseases. After the encapsulation of Dorzolamide, a slight increase in micellar sizes was noted, whereas the encapsulation of Indomethacin led to a decrease in these sizes. Using dynamic light scattering, it was proved that both free and drug-loaded PMs are stable for 30 days of storage at 4 °C. Moreover, in vitro biological tests demonstrated that the obtained PMs are both haemo- and cytocompatible and thus can be used for further in vivo tests. The designed micellar system proved its ability to release the encapsulated drugs in vitro, and the results obtained were validated by in vivo tests carried out on experimental animals, which proved its high effectiveness in reducing intraocular pressure.


Assuntos
Glaucoma , Micelas , Animais , Portadores de Fármacos , Glaucoma/tratamento farmacológico , NAD , Poliésteres , Polietilenoglicóis , Polímeros , Diálise Renal
15.
J Chromatogr A ; 1679: 463383, 2022 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-35940062

RESUMO

We present pseudophase-to-solvent microextraction (PSME) as a simple pressure-driven in-line sample concentration technique in capillary zone electrophoresis (CZE) for small organic anions. The developed technique is like solid-phase extraction; however, the chromatographic phase is a pseudophase, i.e., in-situ cetyltrimethylammonium bromide (CTAB) interfacial micelles. A large volume of sample (e.g., > 12 capillary volumes) prepared in [CTAB] ∼critical micelle concentration was injected into the capillary. The elution and enrichment of analytes trapped in the CTAB coating was facilitated by the high concentration of methanol in the background solution, which was introduced from the outlet end. Co-electroosmotic flow CZE was conducted after the concentrated analytes reached the tip of the inlet. Parameters such as sample loading time and elution time were optimised. Under optimised conditions, the SEFs of 187-573 achieved for the model anions (4-nitrophenol, 4-vinylbenzoic acid, mecoprop, indoprofen, sulfamethizole and sulindac) were comparable to previously reported off-line microextraction techniques. The calculated LOD (S/N = 3), LOQ (S/N = 10), intra-/inter- (n = 6/n = 9, 3 days) day repeatability and linearity (R2s) values in PSME-CZE were 4.2-20.1 ng/mL, 13.8-67.1 ng/mL, 5%, 10% and > 0.990, respectively. The PSME-CZE of fortified urine samples showed % recovery values of 93-108% with %RSDs (n = 3) of 4-10% for the model analytes.


Assuntos
Eletro-Osmose , Eletroforese Capilar , Ânions , Cetrimônio , Micelas , Solventes
16.
Cell Mol Biol (Noisy-le-grand) ; 68(3): 24-33, 2022 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-35988192

RESUMO

The study was to probe into the application of ultrasound technique in gestational diabetes mellitus (GDM) and research the progress of PEG-PCL nano micelle and ultrasound technique. METHOD: 210 patients with a singleton pregnancy fetus, who received the fetal echocardiography in Yuhang District First People's Hospital from March 2019 to March 2020, were selected as the subjects, including 101 fetuses who were confirmed as gestational diabetes mellitus(GDM), and 109 normal fetuses (control group). The ultrasound cardiogram technique was employed to detect the thickness of the fetus ventricle septum, mitral/tricuspid annular displacement, left/right TEI indexes, and so on. The mean value of three cardiac cycles was taken as the test results. Finally, SPSS17.0 software was applied to the analysis of data. The nano micelle was made from the amphiphilic block copolymers (PEG-PCL) using the dialysis method/solvent evaporation method. The nanoscale ultrasound contrast agent was prepared from Decafluoropentane which was imaging gas. The characterizations were studied using the optical microscope, and transmission electron microscopy (TEM). The temperature sensitivity and ultrasound sensitivity of the nano-ultrasound contrast agent were analyzed with the particle size as the evaluation index. The in-vitro ultrasound contrast experiment was conducted to study the contrast-enhanced effect. RESULTS: The fetal Tei index of the case group was higher than that of the control group, of which P<0.05 had statistical significance. However, the thickness of the fetus ventricle septum, Em, Am, and Em/Am of mitral/tricuspid annular were not significantly different from those of the control group (P>0.05). The nano ultrasonic contrast agent prepared through the ultrasonic injection method had a uniform particle size and a hollow shell-core structure under an electron projection microscope. The particle size of the nano-ultrasound contrast agent varied with temperature, and its microbubbles were generated under ultrasonic conditions. As compared with the blank degassed water group, a real linear echo appeared inside the contrast agent group, with small and even echo spots. The back echo remained with no obvious attenuation and lasted for a longer period. However, the blank degassed group had no distinct echo intensity and spot. CONCLUSION: PEG-PCL nano-ultrasound contrast agent achieved an excellent imaging effect; there was no obvious change to heart function and structure of the fetus, when gestational diabetes pregnant had blood sugar perfectly controlled, however, the fetus's heart function may change in the last trimester.


Assuntos
Diabetes Gestacional , Meios de Contraste , Diabetes Gestacional/diagnóstico por imagem , Feminino , Feto , Humanos , Micelas , Gravidez , Ultrassonografia Pré-Natal/métodos
17.
Drug Deliv ; 29(1): 2658-2670, 2022 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-35975300

RESUMO

Glioblastoma is rather recalcitrant to existing therapies and effective interventions are needed. Here we report a novel microenvironment-responsive micellar system (ch-K5(s-s)R8-An) for the co-delivery of the radiosensitizer Dbait and the chemotherapeutic doxorubicin (DOX) to glioblastoma. Accordingly, the ch-K5(s-s)R8-An/(Dbait-DOX) micelles plus radiotherapy (RT) treatment resulted in a high degree of apoptosis and DNA damage, which significantly reduced cell viability and proliferation capacity of U251 cells to 64.0% and 16.3%, respectively. The angiopep-2-modified micelles exhibited substantial accumulation in brain-localized U251 glioblastoma xenografts in mice compared to angiopep-2-lacking micelles. The ch-K5(s-s)R8-An/(Dbait-DOX) + RT treatment group exhibited the smallest tumor size and most profound tumor tissue injury in orthotopic U251 tumors, leading to an increase in median survival time of U251 tumor-bearing mice from 26 days to 56 days. The ch-K5(s-s)R8-An/(Dbait-DOX) micelles can be targeted to brain-localized U251 tumor xenografts and sensitize the tumor to chemotherapy and radiotherapy, thereby overcoming the inherent therapeutic challenges associated with malignant glioblastoma.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Radiossensibilizantes , Animais , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/radioterapia , Linhagem Celular Tumoral , Quimiorradioterapia/métodos , Doxorrubicina , Glioblastoma/tratamento farmacológico , Glioblastoma/radioterapia , Humanos , Camundongos , Micelas , Radiossensibilizantes/farmacologia , Microambiente Tumoral
18.
World J Gastroenterol ; 28(25): 2867-2880, 2022 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-35978871

RESUMO

Despite the significant progress in cancer therapy, colorectal cancer (CRC) remains one of the most fatal malignancies worldwide. Chemotherapy is currently the mainstay therapeutic modality adopted for CRC treatment. However, the long-term effectiveness of chemotherapeutic drugs has been hampered by their low bioavailability, non-selective tumor targeting mechanisms, non-specific biodistribution associated with low drug concentrations at the tumor site and undesirable side effects. Over the last decade, there has been increasing interest in using nanotechnology-based drug delivery systems to circumvent these limitations. Various nanoparticles have been developed for delivering chemotherapeutic drugs among which polymeric micelles are attractive candidates. Polymeric micelles are biocompatible nanocarriers that can bypass the biological barriers and preferentially accumulate in tumors via the enhanced permeability and retention effect. They can be easily engineered with stimuli-responsive and tumor targeting moieties to further ensure their selective uptake by cancer cells and controlled drug release at the desirable tumor site. They have been shown to effectively improve the pharmacokinetic properties of chemotherapeutic drugs and enhance their safety profile and anticancer efficacy in different types of cancer. Given that combination therapy is the new strategy implemented in cancer therapy, polymeric micelles are suitable for multidrug delivery and allow drugs to act concurrently at the action site to achieve synergistic therapeutic outcomes. They also allow the delivery of anticancer genetic material along with chemotherapy drugs offering a novel approach for CRC therapy. Here, we highlight the properties of polymeric micelles that make them promising drug delivery systems for CRC treatment. We also review their application in CRC chemotherapy and gene therapy as well as in combination cancer chemotherapy.


Assuntos
Antineoplásicos , Neoplasias Colorretais , Nanopartículas , Neoplasias , Antineoplásicos/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Portadores de Fármacos , Sistemas de Liberação de Medicamentos , Humanos , Micelas , Neoplasias/tratamento farmacológico , Polímeros/uso terapêutico , Distribuição Tecidual
19.
J Dairy Sci ; 105(9): 7266-7275, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35931485

RESUMO

The effect of ethanol on milk has been shown to be temperature-dependent, with higher ethanol concentrations and temperatures reversibly dissociating casein micelles. This work looked to expand on this knowledge, while also demonstrating the efficiency and precision of a custom-made continuous monitoring unit that combines solutions at defined concentrations and temperatures while measuring various parameters (i.e., absorbance, fluorescence, pressure). Caseins were found to self-associate at moderate ethanol concentrations (i.e., 12-36% vol/vol ethanol); however, they dissociated and remained in the serum at higher ethanol concentrations (≥48% vol/vol) and temperatures (24 and 34°C). Although serum casein content was found to be positively correlated with protein hydrophobicity, the addition of ethanol only increased protein hydrophobicity when the sample was held at high temperatures (34-64°C). Overall, the greatest dissociation of casein micelles was found between 40 and 60% (vol/vol) ethanol concentration at elevated temperatures (≥34°C). At these ethanol concentrations and temperatures, skim milk absorbance was minimized, serum casein content (including ß-casein content) was maximized, and protein hydrophobicity reached a relative maximum.


Assuntos
Caseínas , Micelas , Animais , Etanol/farmacologia , Concentração de Íons de Hidrogênio , Leite
20.
Inorg Chem ; 61(33): 13115-13124, 2022 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-35950896

RESUMO

Toxicity induced by inorganic arsenic as AsO33- (iAsIII) is of global concern. Reliable detection of the maximum allowed contaminant level for arsenic in drinking water and in the cellular system remains a challenge for the water quality management and assessment of toxicity in the cellular milieu, respectively. A new Ir(III)-based phosphorescent molecule (AS-1; λExt = 415 nm and λEms = 600 nm, Φ = 0.3) is synthesized for the selective detection of iAsIII in an aqueous solution with a ratiometric luminescence response even in the presence of iAsV and all other common inorganic cations and anions. The relatively higher affinity of the thioimidazole ligand (HPBT) toward iAsIII led to the formation of a fluorescent molecule iAsV-HPBT (λExt = 415 nm and λEms = 466 nm, Φ = 0.28) for the reaction of iAsIII and AS-1. An improved limit of quantitation (LOQ) down to 0.2 ppb is achieved when AS-1 is used in the CTAB micellar system. Presumably, the cationic surfactants favor the localization of AS-1@CTABMicelle in mitochondria of MCF7 cells, and this is confirmed from the images of the confocal laser fluorescence scanning microscopic studies. Importantly, cell viability assay studies confirm that AS-1@CTABMicelle induces dose-dependent detoxification of iAsIII in live cells. Further, luminescence responses at 466 nm could be utilized for developing a hand-held device for the in-field application. Such a reagent that allows for ratiometric detection of iAsIII with LOQ of 2.6 nM (0.5 ppb) in water, as well as helps in visualizing its distribution in mitochondria with a detoxifying effect, is rather unique in contemporary literature.


Assuntos
Arsênio , Arsênio/toxicidade , Cetrimônio , Indicadores e Reagentes , Micelas , Mitocôndrias
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