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1.
Spectrochim Acta A Mol Biomol Spectrosc ; 324: 124965, 2025 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-39153345

RESUMO

AFB1 is a harmful substance that can be found in agricultural products and can seriously affect human health, even in trace amounts. Therefore, monitoring AFB1 levels to ensure food safety and protect public health is crucial. New, highly reliable, selective, and rapid detection methods are needed to achieve this goal. Our work involves the development of a polymeric membrane sensor using radical polymerization that can accurately detect AFB1. Various spectroscopic techniques (Fourier transform infrared spectroscopy (FT-IR) and scanning electron microscopy (SEM)) were used to obtain information about the structural and morphological properties of the prepared sensor. The sensor displayed fluorescence selectively responsive to AFB1 at the excitation wavelength of 376 nm and emission wavelength of 423 nm. The polymeric fluorescence sensor showed good sensitivity and a wide linear range from 9.61 × 10-10 and 9.61 × 10-9 mol/L for AFB1quantification. The limit of detection (LOD) is as low as 3.84 × 10-10 mol/L for AFB1. Other mycotoxins, such as aflatoxin B2 and aflatoxin G1, did not interfere with the sensor's high selectivity towards AFB1. To test the sensor's effectiveness in detecting AFB1 in real samples, three different grain samples - peanuts, hazelnut butter, and peanuts with a sauce known to contain AFB1 - were utilized. The results were satisfactory and demonstrated that the sensor can be successfully employed in real samples, with an error range of 0.43 % to 12.10 %.


Assuntos
Aflatoxina B1 , Limite de Detecção , Espectrometria de Fluorescência , beta-Ciclodextrinas , Aflatoxina B1/análise , Espectrometria de Fluorescência/métodos , beta-Ciclodextrinas/química , Espectroscopia de Infravermelho com Transformada de Fourier , Contaminação de Alimentos/análise , Grão Comestível/química , Polímeros/química
2.
Mol Pharm ; 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39353049

RESUMO

Melanoma is an aggressive skin cancer notorious for high levels of drug resistance. Additionally, current treatments such as immunotherapies are often associated with numerous adverse side effects. The use of nitric oxide (NO) may represent an attractive treatment for melanoma due to NO's various anticancer properties, unlikeliness to foster resistance, and limited toxicity toward healthy tissues. The anticancer effects of chemical NO donors have been explored previously but with limited understanding of the needed characteristics for exerting optimal antimelanoma activity. Herein, the in vitro therapeutic efficacy of three macromolecular NO donor systems (i.e., cyclodextrin, mesoporous silica nanoparticles, and hyaluronic acid) with tunable NO-release kinetics was explored by evaluating skin permeation along with toxicity against melanoma and healthy skin cells. Cytotoxicity against melanoma cells was dependent on NO payload and not donor identity or NO-release kinetics. In contrast, cytotoxicity against healthy cells was primarily influenced by the macromolecular NO donor, with cyclodextrin- and hyaluronic acid-based NO donors having the highest therapeutic indices. In vitro skin permeation was influenced by both the size and charge of the NO donor, with smaller, more neutral donors resulting in greater permeation. A Pluronic F127 organogel was optimized for the delivery of a cyclodextrin-based NO donor. Delivery of the NO donor in this manner resulted in increased in vitro skin permeation and reduced tumor growth in an in vivo model.

3.
Drug Des Devel Ther ; 18: 4345-4358, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39359484

RESUMO

Purpose: We aimed to prepare a ß-cyclodextrin (ß-CD) polymer using radical polymerization with co-monomers, 6-deoxy-6-(2-methacryloyloxyethylsuccinamide)-ß-cyclodextrin (CD-MSAm) and N,N,N-trimethyl-N-(2-hydroxy-3-metacryloyloxopropyl)-ammonium chloride (QA) to design cyclodextrins suitable for use in ophthalmology. In addition, we evaluated their solubility and inclusion properties with rebamipide (REB), a poorly soluble drug, and investigated the usefulness of the ß-CD polymer and REB (REB@CDQA) combination in treating dry eye. Methods: The ß-CD polymer (CD-MSAm-co-QA, CDQA) based on CD-MSAm/QA was prepared via radical polymerization, and the usefulness of REB@CDQA in treating dry eye was evaluated using a rabbit treated with N-acetylcysteine (dry eye model). Results: The solubility of the CDQA powder was higher than that of the ß-CD powder, and 80 nm colloids were observed in the CDQA solution. No corneal toxicity was observed in human corneal epithelial cells or rat corneas treated with 0.2% CDQA solution. The levels of REB dissolved in the CDQA solution were higher than those of the ß-CD solution. Moreover, the application of the CDQA solution enhanced REB retention in the cornea and attenuated the transcorneal penetration of REB. In addition, instillation of REB@CDQA enhanced the volume of the lacrimal fluid and normalized the reduced mucin levels in the dry eye model. The extent of tear film breakup was attenuated by REB@CDQA instillation. Conclusion: The CDQA solution enhanced the solubility of REB, and the combination of CDQA and REB enhanced the drug content in the corneal tissue. Moreover, the therapeutic effect on dry eye was higher than that of REB suspensions without CDQA.


Assuntos
Acetilcisteína , Alanina , Modelos Animais de Doenças , Síndromes do Olho Seco , Quinolonas , Animais , Coelhos , Síndromes do Olho Seco/tratamento farmacológico , Quinolonas/farmacologia , Quinolonas/química , Quinolonas/administração & dosagem , Acetilcisteína/farmacologia , Acetilcisteína/química , Acetilcisteína/administração & dosagem , Humanos , Alanina/análogos & derivados , Alanina/química , Alanina/farmacologia , Alanina/administração & dosagem , Polímeros/química , Polímeros/farmacologia , Ciclodextrinas/química , Ciclodextrinas/farmacologia , Polimerização , Ratos , Solubilidade , Cátions/química , beta-Ciclodextrinas/química , Córnea/efeitos dos fármacos , Córnea/metabolismo , Masculino , Estrutura Molecular
4.
Int J Pharm ; 666: 124787, 2024 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-39362296

RESUMO

Nanoparticles (NPs) have gained significant attention in recent years due to their potential applications in pharmaceutical formulations, drug delivery systems, and various biomedical fields. The versatility of colloidal NPs, including their ability to be tailored with various components and synthesis methods, enables drug delivery systems to achieve controlled release patterns, improved solubility, and increased bioavailability. The review discusses various types of NPs, such as nanocrystals, lipid-based NPs, and inorganic NPs (i.e., gold, silver, magnetic NPs), each offering unique advantages for drug delivery. Despite the promising potential of NPs, challenges such as physical instability and the need for surface stabilization remain. Strategies to overcome these challenges include the use of surfactants, polymers, and cyclodextrins (CDs). This review highlights the role of CDs in stabilizing colloidal NPs and enhancing drug solubility. The combination of CDs with NPs presents a synergistic approach that enhances drug delivery and broadens the range of biomedical applications. Additionally, the potential of CDs to enhance the stability and therapeutic efficacy of colloidal NPs, making them promising candidates for advanced drug delivery systems, is comprehensively reviewed.

5.
Chemistry ; : e202403232, 2024 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-39382344

RESUMO

Amphiphilic supramolecular materials based on biodegradable cyclodextrins (CDs) have been known to self-assemble into different types of thermotropic liquid crystals, including smectic and hexagonal columnar mesophases. Previous studies on amphiphilic CDs bearing 14 aliphatic chains at the primary face and 7 oligoethylene glycol (OEG) chains at the secondary face showed that the stability of the mesophase can be rationally tuned through implemation of terminal functional groups to the OEG chains. Here, we report the syntheses of first examples of crown ether-functionalized amphiphilic cyclodextrins that unexpectedly form thermotropic bicontinuous cubic phases. This constitutes the first reported examples of cyclodextrins forming such phases, which are potentially capable of 3D ion transport. Lithium composites were made to assess lithium conduction in the material. XRD revealed the added lithium salt destabilizes the cubic phase in favour of the smectic phase. Solid-state NMR studies showed that these materials conduct lithium ions with a very low activation energy.

6.
J Chromatogr A ; 1736: 465394, 2024 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-39366032

RESUMO

Cyclodextrin-based stationary phases are important chiral selectors in liquid chromatography. These chiral selectors are most commonly used in the reversed-phase mode because native cyclodextrin assumes a torus conformation with a hydrophobic cavity, facilitating inclusion complexation in aqueous environments. However, the value of native and aliphatic-derivatized cyclodextrins in other modes, such as the normal phase liquid chromatography (NPLC) or super/subcritical fluid chromatography (SFC), remains unexplored. In this work, we report chiral separations of pharmaceutically relevant compounds with the 1,4-dihydropyridine (DHP) scaffold on a 2-hydroxypropyl-ß-cyclodextrin (CD-RSP) stationary phase in NPLC and SFC modes. Although CD-RSP is conventionally considered only effective in the reversed-phase mode, we show that these compounds tend to separate better in other modes. This is particularly apparent for analytes with hydrogen-bonding moieties. We propose that the separation mechanism primarily depends on external adsorption rather than inclusion complexation. The negligible impact of a complexation-competitive additive on retention in non-aqueous modes further supports this claim. Additionally, van Deemter analysis demonstrated the efficiency and environmental benefit of using this stationary phase in the SFC mode, further highlighting the promise of aliphatic derivatized cyclodextrin stationary phases for greener separations.

7.
Sci Rep ; 14(1): 23046, 2024 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-39367103

RESUMO

Corneal ulcers, whether melting or indolent, are common in humans and companion animals. Treatment involves local administration of antibiotic eye drops and corneal healing drugs. Compared to traditional treatments for ulcerative keratitis, herbal medicines offer unique advantages, such as potent anti-inflammatory effects and inhibition of proinflammatory cytokines. Curcumin, extracted from the Curcuma Longa plant, possesses extensive pharmacological properties, such as anti-inflammatory, anti-cancer, and antioxidant properties, and is used in various medicines. In this study, we developed a novel ophthalmic drop hydrogel using a formulation of Curcumin NPs encapsulated with ß-cyclodextrin and hyaluronic acid, to accelerate corneal healing and improve the quality of healed structures. The formation of Curcumin NPs into Hyaluronic acid-based hydrogels was characterized by zeta, FTIR, and scanning electron microscope (SEM) analyses. A total of 25 healthy male New Zealand Albino rabbits were experimentally induced with ulcerative keratitis and treated individually with topical medication. Rabbits were divided into five groups. Fluorescein dye staining, corneal clarity score, Schirmer tear test, proinflammatory cytokine measurement, and pathologic factors assessments were used to evaluate the optimised Curcumin NPs with ß-cyclodextrin in Hyaluronic acid hydrogel. Our results demonstrated that the optimized Curcumin NPs with ß-cyclodextrin in hyaluronic acid hydrogel significantly reduced the frequency of medication administration compared to conventional therapies, enhancing the quality of healed structures and effectively treating ulcerative keratitis. All findings in this study provide new insight into designing and fabricating novel ophthalmic medicine for ulcerative keratitis for topical usage.


Assuntos
Úlcera da Córnea , Curcumina , Modelos Animais de Doenças , Ácido Hialurônico , Hidrogéis , Nanopartículas , Animais , Coelhos , Curcumina/farmacologia , Curcumina/química , Curcumina/administração & dosagem , Ácido Hialurônico/química , Nanopartículas/química , Hidrogéis/química , Úlcera da Córnea/tratamento farmacológico , Úlcera da Córnea/patologia , Masculino , Cicatrização/efeitos dos fármacos , Soluções Oftálmicas/química , Córnea/efeitos dos fármacos , Córnea/patologia , Córnea/metabolismo , beta-Ciclodextrinas/química , Citocinas/metabolismo
8.
Food Chem ; 464(Pt 1): 141553, 2024 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-39406140

RESUMO

Cyclolinopeptides (CLs) have anti-inflammatory, anti-osteoporosis, and anti-tumor effects, however, low water and oil solubility greatly limit their application. Herein, CLs-loaded ß-cyclodextrin (ß-CD) emulsions were prepared with different oil phases. The in vitro digestibility, cellular absorption, and anti-inflammatory effects were evaluated. Camellia oil diacylglycerol (CO DAG) showed enhanced dissolving ability for CLs due to high polarity. ß-CD formed inclusion complexes with DAG through hydrogen bond and the emulsions showed smaller size and higher physical stability with 50 % (w/w) oil. The in vitro digestibility of the DAG emulsion was increased and the CLs' bioavailability was 13.6-fold higher than CLs in oil. The CLs-loaded Pickering emulsion digesta exhibited a higher nitric oxides (NO) inhibition rate (58.62 %) and Caco-2 cell penetration (3.09 × 10-6 cm/s). Therefore, emulsion formulated with ß-cyclodextrin and DAG can effectively improve the solubility and bioavailability of CLs, which has significant potential for application in functional foods and pharmaceutical industry.

9.
Int J Pharm ; : 124809, 2024 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-39384028

RESUMO

Development of novel active pharmaceutical ingredients (API) for oral use often face challenges due to low bioavailability. Nanoparticle-based drug delivery systems and cyclodextrin (CD) encapsulation offer promising solutions by enhancing API solubility or dissolution rates. Porous silicon nanoparticles have shown potential to encapsulate APIs in their amorphous form within pores, improving dissolution rates compared to crystalline counterparts. A novel synthesis approach, circumventing the expensive and tedious Si wafer material synthesis, has been developed using centrifugal Chemical Vapor Deposition (cCVD). Herein, various cCVD Si particles were evaluated for their ability to enhance the dissolution rate of the model drugs celecoxib (CEL), phenytoin (PHT), griseofulvin (GRI), diclofenac (DCF), and naproxen (NAP). Our findings demonstrate increased dissolution rates of all tested APIs when formulated with cCVD Si particles, compared to free API in pH 7.4 or pH 2.0. Particle characteristics were largely retained after loading, and the solid state of the loaded APIs were evaluated using Differential Scanning Calorimetry (DSC). Dissolution kinetics were influenced by the particle properties, mass loading and API characteristics. Loading of CD-CEL, -GRI and -DCF complexes into the cCVD Si particles showed a potential for further enhanced dissolution rates, representing the first reported investigation of this combination. In conclusion, the cCVD Si particles are promising for improving the dissolution rate of poorly soluble drugs, potentially due to precipitation of amorphous or metastable forms. Further enhancements were observed upon loading CD-drug complexes, thereby offering promising strategies for optimizing drug bioavailability.

10.
Biochim Biophys Acta Bioenerg ; 1866(1): 149516, 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-39357779

RESUMO

Recent patch-clamp studies of mitoplasts have challenged the traditional view that classical chemical uncoupling (by e.g. FCCP or DNP) is due to the protonophoric property of these substances themselves. These studies instead suggest that in brown-fat mitochondria, FCCP- and DNP-induced uncoupling is mediated through activation of UCP1 (and in other tissues by activation of the adenine nucleotide transporter). These studies thus advocate an entirely new paradigm for the interpretation of standard bioenergetic experiments. To examine whether these patch-clamp results obtained in brown-fat mitoplasts are directly transferable to classical isolated brown-fat mitochondria studies, we investigated the effects of FCCP and DNP in brown-fat mitochondria from wildtype and UCP1 KO mice, comparing the FCCP and DNP effects with those of a fatty acid (oleate), a bona fide activator of UCP1. Whereas the sensitivity of brown-fat mitochondria to oleate was much higher in UCP1-containing than in UCP1 KO mitochondria, there was no difference in sensitivity to FCCP and DNP between these mitochondria, neither in oxygen consumption rate nor in membrane potential studies. Correspondingly, the UCP1-dependent ability of GDP to competitively inhibit activation by oleate was not seen with FCCP and DNP. It would thus be premature to abandon the established bioenergetic interpretation of chemical uncoupler effects in classical isolated brown-fat mitochondria-and probably also generally in this type of mitochondrial study. Understanding the molecular and structural reasons for the different outcomes of mitoplast and mitochondrial studies is a challenging task.

11.
Anal Chim Acta ; 1329: 343249, 2024 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-39396310

RESUMO

BACKGROUND: As the derivatives of cyclodextrin (CD), cyclodextrin polymers (CDPs) effectively increase the concentration of CD units and construct supramolecular structures with unique stereoselectivity by the structure design. CDPs have shown significant potential in chiral separation, however, the process of stereoselective interactions on chiral stationary phases (CSPs) and the specific contribution of intermolecular forces are still a challenge issue. A comprehensive understanding of the chiral recognition mechanism of CDPs will help to optimize chiral separation conditions and design new CSPs. RESULTS: The star CDP with a supermolecular structure was synthesized by grafting ß-CD onto the external 6-position hydroxyl groups using ß-CD as the parent nucleus. The enhanced host-guest recognition ability of CD supramolecular polymer structure provided better inclusion interaction and increased chiral recognition of the isomers. The Star-CD CSP with star CDP as a chiral ligand performed satisfactory stereoisomer separation ability with the separation factor (α) up to 2.0 for various quinoline alkaloid isomers and 1.89 for catechins. To elucidate its chiral separation mechanism, molecular docking was used to construct the three-dimensional visual models of the binding sites and the contribution of non-covalent interactions between Star-CD CSP and quinoline alkaloid isomers. In addition, the formation sites of non-covalent interactions on the CD monomers of the polymer side chains were confirmed from the actual geometric structure by analyzing the NMR chemical shift changes before and after the formation of complexes between Star-CD polymers and isomers. Combined with the mutual evidence of molecular simulation and chiral NMR, the specific recognition mechanism of selector-selectand complexes was comprehensively expounded. SIGNIFICANCE: The multi-mode CSP based on cyclodextrin supramolecular structure provides new ideas for the stereoisomeric separation of complex chiral components with multiple chiral centers in natural products. Not limited to the macroscopic performance of the chromatographic separation, molecular docking explored the theoretical model of chiral recognition from the molecular level. The chiral NMR analysis confirmed the credibility of the model from the geometry structure, and then the recognition mechanism of multi-mode CSP was fully elaborated combining the above three aspects.

12.
Luminescence ; 39(10): e4917, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39380243

RESUMO

This study introduces a remarkably simple, green, and highly sensitive inclusion complex based spectrofluorimetric method for analyzing two sodium glucose cotransporter-2 (SGLT2) inhibitors: empagliflozin (EGF) and dapagliflozin (DGF). The method utilizes beta-cyclodextrin (ß-CD) complexation to enhance the native fluorescence of EGF and DGF in aqueous solutions, resulting in 11.0-fold and 9.0-fold intensity increases, respectively. Fluorescence measurements were conducted at 301 nm emission following 230 nm excitation for both drugs. The method demonstrates excellent linearity (0.9994 for EGF and 0.9993 for DGF) over concentration ranges of 5.0-250.0 ng/mL and 10.0-300.0 ng/mL, with low detection limits of 1.05 and 1.38 ng/mL for EGF and DGF, respectively. The method's versatility was validated through successful application in pharmaceutical formulations, content uniformity testing, and biological fluids. This eco-friendly approach primarily uses water as a solvent and requires minimal reagents. The method's environmental impact was comprehensively evaluated using the analytical eco-scale, green analytical procedure index (GAPI), and analytical greenness metric (AGREE).


Assuntos
Compostos Benzidrílicos , Glucosídeos , Inibidores do Transportador 2 de Sódio-Glicose , Espectrometria de Fluorescência , beta-Ciclodextrinas , Inibidores do Transportador 2 de Sódio-Glicose/análise , Compostos Benzidrílicos/análise , Compostos Benzidrílicos/química , Glucosídeos/análise , beta-Ciclodextrinas/química , Humanos , Química Verde
13.
Int J Mol Sci ; 25(19)2024 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-39409039

RESUMO

Kidney dysfunction leads to the retention of metabolites within the blood that are not effectively cleared with conventional hemodialysis. Magnetic nanoparticle (MNP)-based absorbents have inherent properties that make them amenable to capturing toxins in the blood, notably a large surface area that can be chemically modified to enhance toxin capture and the ability to be easily collected from the blood using an external magnetic field. Cyclodextrins (CDs) present a chemical structure that facilitates the binding of small molecules. However, the hemocompatibility of MNPs modified with films composed of different native types of CDs (α, ß, or γ) has not yet been investigated, which is information crucial to the potential clinical application of MNPs to supplement hemodialysis. To this end, films of α-, ß-, or γ-CDs were formed on MNPs and characterized. The impact of these films on the adsorbed protein structure, composition of key adsorbed proteins, and clotting kinetics were evaluated. It was found that modified MNPs did not significantly affect the secondary structure of some proteins (albumin, lysozyme, α-lactalbumin). The adsorbed proteome from platelet-poor human plasma was evaluated as a function of film properties. Compared to non-modified nanoparticles, CD-modified MNPs exhibited a significant decrease in the adsorbed protein per surface area of MNPs. The immunoblot results showed variations in the adsorption levels of C3, fibrinogen, antithrombin, Factor XI, and plasminogen across CD-modified MNPs. The hemocompatibility experiments showed that CD-modified MNPs are compatible with human whole blood, with no significant impact on platelet activation, hemolysis, or hemostasis.


Assuntos
Nanopartículas de Magnetita , Humanos , Adsorção , Nanopartículas de Magnetita/química , Ciclodextrinas/química , Coagulação Sanguínea/efeitos dos fármacos , Teste de Materiais , gama-Ciclodextrinas/química , Materiais Biocompatíveis/química , beta-Ciclodextrinas/química , alfa-Ciclodextrinas/química
14.
Int J Mol Sci ; 25(19)2024 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-39409162

RESUMO

Cyclodextrins (CDs) are ubiquitous excipients, constituted of cyclic glucopyranose units, and possess a unique dual nature, that of a hydrophobic interior and a hydrophilic exterior. This enables their interaction with lipid-affinitive compounds and hydrophilic compounds, thereby augmenting their application in pharmaceutical formulations as agents for improving solubility, as well as fundamental elements of advanced drug delivery systems. Additionally, CDs, upon suitable modification, can strategically participate in the interaction with cellular components and physical barriers, such as the blood-brain barrier, where their intricate and multifunctional engagement leads to various biological impacts. This review consolidates the crucial features of CDs and their derivatives, and summarizes the applications of them as drug delivery systems in neurodegenerative disorders, emphasizing their notable potentials.


Assuntos
Ciclodextrinas , Sistemas de Liberação de Medicamentos , Doenças Neurodegenerativas , Ciclodextrinas/química , Doenças Neurodegenerativas/tratamento farmacológico , Doenças Neurodegenerativas/metabolismo , Humanos , Sistemas de Liberação de Medicamentos/métodos , Barreira Hematoencefálica/metabolismo , Animais , Portadores de Fármacos/química
15.
Foods ; 13(19)2024 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-39410113

RESUMO

Hemin, a heme-like compound with significant biological activity, shows promise as an iron supplement for humans. Nonetheless, its poor solubility in water greatly impedes its absorption and utilization. To surmount this obstacle, researchers have chosen various cyclodextrins with distinct cavity sizes and derivative groups to act as hosts, forming inclusion complexes with hemin chloride. Among these, γ-cyclodextrin has been identified as the optimal carrier, based on a thorough evaluation of its encapsulation efficiency, solubility, and molecular docking. Multiple characterization techniques further confirmed the formation of these inclusion complexes. Results from IEC-6 cell experiments indicated that the cytotoxicity of the inclusion complexes was lower than that of FeSO4. Static and dynamic gastrointestinal simulation digestion systems were established, and the results showed that the bioavailability of the inclusion complex was significantly higher than that of raw hemin. Additionally, only about 0.29% of hemin chloride is digested by gastric enzymes, whereas 9.52% is digested by pancreatic enzymes in the static gastrointestinal simulation digestion system, with similar outcomes observed in the dynamic system. These findings suggest that targeted digestion in the intestine significantly enhances the bioavailability of hemin chloride by forming inclusion complexes in vitro.

16.
Molecules ; 29(19)2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-39407584

RESUMO

In the present report, we have described the synthesis of N-aminopolyhydroquinoline (N-PHQ) derivatives using highly efficient ß-cyclodextrin (ß-CD) as a catalyst by the Hantzsch condensation of substituted aromatic aldehydes, dimedone, and hydrazine hydrate in one pot. The reactions were completed in a shorter time without the generation of any other byproduct. The synthesized N-PHQs were washed thoroughly with distilled water and recrystallized with ethanol to get highly purified products (as crystals). The structure of the synthesized N-PHQs was established by using advanced spectroscopic techniques like FT-IR, NMR (1H, 13C, DEPT, COSY, and HSQC), ESI-MS, and Elemental Analyzer. The N-PHQs derivatives demonstrated moderate to excellent resistance against the tested strains (both fungal as well as bacterial). The presence of polar groups, which are able to form H-bonds, attached to the phenyl ring like -NO2 (4b and 4c), and -OMe (4i, 4j, and 4k) exhibits excellent activity, which is comparable to standard drugs, amoxicillin and fluconazole.


Assuntos
Anti-Infecciosos , Testes de Sensibilidade Microbiana , beta-Ciclodextrinas , beta-Ciclodextrinas/química , beta-Ciclodextrinas/síntese química , Catálise , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Anti-Infecciosos/síntese química , Estrutura Molecular , Quinolinas/química , Quinolinas/síntese química , Quinolinas/farmacologia , Fungos/efeitos dos fármacos , Bactérias/efeitos dos fármacos , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/síntese química
17.
Molecules ; 29(19)2024 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-39407641

RESUMO

A novel sandwich-type electrochemical aptasensor based on supramolecularly immobilized affinity bioreceptor was prepared via host-guest interactions. This method utilizes an adamantane-modified, target-responsive hairpin DNA aptamer as a capture molecular receptor, along with a perthiolated ß-cyclodextrin (CD) covalently attached to a gold-modified electrode surface as the transduction element. The proposed sensing strategy employed an enzyme-modified aptamer as the signalling element to develop a sandwich-type aptasensor for detecting prostate-specific antigen (PSA). To achieve this, screen-printed carbon electrodes (SPCEs) with electrodeposited reduced graphene oxide (RGO) and gold nanoferns (AuNFs) were modified with the CD derivative to subsequently anchor the adamantane-modified anti-PSA aptamer via supramolecular associations. The sensing mechanism involves the affinity recognition of PSA molecules on the aptamer-enriched electrode surface, followed by the binding of an anti-PSA aptamer-horseradish peroxidase complex as a labelling element. This sandwich-type arrangement produces an analytical signal upon the addition of H2O2 and hydroquinone as enzyme substrates. The aptasensor successfully detected the biomarker within a concentration range of 0.5 ng/mL to 50 ng/mL, exhibiting high selectivity and a detection limit of 0.11 ng/mL in PBS.


Assuntos
Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , Técnicas Eletroquímicas , Ouro , Grafite , Antígeno Prostático Específico , Antígeno Prostático Específico/análise , Antígeno Prostático Específico/química , Aptâmeros de Nucleotídeos/química , Técnicas Eletroquímicas/métodos , Técnicas Biossensoriais/métodos , Humanos , Ouro/química , Grafite/química , Eletrodos , Limite de Detecção , Masculino , Nanopartículas Metálicas/química
18.
Int J Mol Sci ; 25(19)2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39408919

RESUMO

Chlortetracycline hydrochloride (CTC) is a broad-spectrum tetracycline antibiotic with a wide range of antibacterial activities. Due to low solubility, poor stability, and low bioavailability, clinical preparation development is limited. We sought to improve these solubility and dissolution rates by preparing solid dispersions. A hydrophilic polymer was selected as the carrier, and a solid dispersion was prepared using a medium grinding method, with samples characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), powder X-ray diffraction (PXRD), Fourier-transform infrared spectroscopy (FT-IR), and particle size distribution (PSD). To maximize CTC solubility and stability, different polymer types and optimal drug-to-polymer ratios were screened. The solubility of optimized povidone K30 (PVPK30) (1/0.75, w/w)-, hydroxypropyl-ß-cyclodextrin (HP-ß-CD) (1/2, w/w)-, and gelatin (1/1, w/w)-based solid dispersions was 6.25-, 7.7-, and 3.75-fold higher than that of pure CTC powder, respectively. Additionally, in vitro dissolution studies showed that the gelatin-based solid dispersion had a higher initial dissolution rate. SEM and PS analyses confirmed that this dispersion had smaller and more uniform particles than PVPK30 and HP-ß-CD dispersions. Therefore, successful solid polymer dispersion preparations improved the CTC solubility, dissolution rates, and stability, which may have potential as drug delivery systems.


Assuntos
Clortetraciclina , Polímeros , Solubilidade , Clortetraciclina/química , Polímeros/química , Espectroscopia de Infravermelho com Transformada de Fourier , 2-Hidroxipropil-beta-Ciclodextrina/química , Tamanho da Partícula , Difração de Raios X , Termogravimetria , Varredura Diferencial de Calorimetria , Antibacterianos/química , Povidona/química , Portadores de Fármacos/química , Gelatina/química
19.
J Pharm Sci ; 2024 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-39374691

RESUMO

The stabilization of protein therapeutics against aggregation is crucial for maintaining their efficacy and safety. This study investigated the synergistic effects of cyclodextrins (CDs) and electrolytes at high concentrations on the stabilization of immunoglobulin G (IgG), insulin, and adeno-associated virus (AAV) vectors. The effects of 2-hydroxypropyl-ß-cyclodextrin (HP-ß-CD) combined with various electrolytes were evaluated using human plasma-derived IgG as a model protein. The HP-ß-CD and L(+)-arginine hydrochloride combination synergistically increased the onset temperature of protein aggregation and inhibited the formation of soluble and insoluble aggregates during long-term storage. Notably, this synergistic effect was not observed when sucrose was used instead of HP-ß-CD. Similar synergistic effects were observed with insulin and AAV vectors. The findings suggest that the stabilization mechanism could potentially involve enhanced interactions between HP-ß-CD and IgG, preventing protein-protein interactions. However, the combination did not synergistically improve the solubility of free aromatic amino acids, including tyrosine and tryptophan. This study highlights the potential of using the combination of CDs and electrolytes as a promising formulation strategy for stabilizing complex protein therapeutics. However, further studies are needed to elucidate the underlying mechanisms and generalize the approach to other proteins with varying physicochemical properties.

20.
Spectrochim Acta A Mol Biomol Spectrosc ; 326: 125181, 2024 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-39332182

RESUMO

An efficient Surface-enhanced Raman scattering (SERS) method for the detection of cysteamine hydrochloride (CSH) was developed by synthesizing a composite substrate comprising silver nanoparticles (AgNPs) functionalized with MoS2 and ß-cyclodextrin (ß-CD). The enhanced Raman signals of CSH by ß-CD/MoS2/AgNPs substrate were the contribution of electromagnetic enhancement (EM) as well as chemical enhancement (CM), and the enhancement factor (EF) can reach up to 3.11 × 106 (peak at 633 cm-1). Various instrumental techniques were used to characterize the substrate, such as X-ray diffraction (XRD), thermogravimetric analysis (TGA), transmission electron microscopy (TEM), high-angle annular dark field scanning transmission electron microscopy (HAADF-STEM) and ultraviolet visible (UV-vis). The binding of ß-CD/MoS2/AgNPs and CSH was confirmed by UV-vis and Fourier transform infrared (FT-IR). The optimal experimental conditions were determined by single factor experiments as well as response surface model. The influences of different metal ions and analogous drugs on the detection of CSH were investigated. Under optimum conditions, a good linear correlation (R = 0.9997) was established for CSH in the range of 10.00-1000.00 nmol/L, and the limit of detection (LOD) was as low as 0.78 nmol/L (S/N = 3). The contents of CSH in meat samples were detected. The recovery was 96.6-103.1 %, and the relative standard deviation (RSD) of the measurement was 0.7-3.9 % (n = 7).

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