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1.
ACS Sens ; 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38875528

RESUMO

Even though significant advances have been made, there is still a lack of reliable sensors capable of noninvasively monitoring bilirubin and diagnosing jaundice as the most common neonatal disease, particularly at the point-of-care (POC) where blood sampling from infants is accompanied by serious challenges and concerns. Herein, for the first time, using an easy-to-fabricate/use assay, we demonstrate the capability of curcumin embedded within paper for noninvasive optical monitoring of bilirubin in saliva. The highly selective sensing of the developed sensor toward bilirubin is attributed to bilirubin photoisomerization under blue light exposure, which can selectively restore the bilirubin-induced quenched fluorescence of curcumin. We also fabricated an IoT-enabled hand-held optoelectronic reader to measure and quantify the fluorescence and color signals of our sensor. Clinical analysis on the saliva of 18 jaundiced infants by using our developed smart salivary sensor proved that it is amenable to be widely exploited in POC applications for bilirubin monitoring as there are good correlations between its results with those of reference methods in saliva and blood. Meeting all WHO's REASSURED criteria by our developed sensor makes it a highly promising sensor for smart noninvasive diagnosis and therapeutic monitoring of jaundice, hepatitis, and other bilirubin-induced neurologic diseases at the POC.

2.
Artigo em Inglês | MEDLINE | ID: mdl-38728602

RESUMO

Rapid control of the content of Parkinson's drugs in biological fluids and pharmaceutical formulations is of great importance because changes in the concentration of these drugs affect their bioavailability and biopharmaceutical properties. Therefore, we presented a simple and convenient method for the ratiometric detection of carbidopa and levodopa for carbon dots (CDs) dual-fluorescent emission. Dual-emission CDs were prepared from chitosan using a microwave method, following which the surface was chemically modified with terephthalaldehyde. CDs had two strong well-separated peaks at 445 and 510 nm. The relative measurement of carbidopa and levodopa was based on the static extinction of CDs at 445 nm and increase at 510 nm, respectively. The linear range for carbidopa measurement was 2.5-300 nM, with a limit of detection (LOD) of 2.1 nM, and a relative standard deviation (RSD) of 1.68%. Further, the linear range for levodopa measurement was equal to 3.0-400 nM, with LOD and RSD% of 2.8 nM and 3.5%, respectively. Also, selectivity of ratiometric sensor in the presence of interferences was investigated, which showed that the recovery of carbidopa and levodopa in serum and urine samples has changed between 96.80% and 116.24% with RSD% 0.11-0.77. CDs also provided good results for the determination of carbidopa and levodopa in real samples, and had high selectivity in the presence of possible interferences.

3.
Sci Rep ; 14(1): 10418, 2024 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-38710793

RESUMO

A new drug delivery system using an asymmetric polyethersulfone (PES) membrane modified by SBA-15 and glutamine-modified SBA-15 (SBA-Q) was prepared in this study by the aim of azithromycin delivery enhancement in both in vitro and ex vivo experiments. The research focused on optimizing membrane performance by adjusting critical parameters including drug concentration, membrane thickness, modifier percentage, polymer percentage, and pore maker percentage. To characterize the fabricated membranes, various techniques were employed, including scanning electron microscopy, water contact angle, and tensile strength assessments. Following optimization, membrane composition of 17% PES, 2% polyvinylpyrrolidone, 1% SBA-15, and 0.5% SBA-Q emerged as the most effective. The optimized membranes demonstrated a substantial increase in drug release (906 mg/L) compared to the unmodified membrane (440 mg/L). The unique membrane structure, with a dense top layer facilitating sustained drug release and a porous sub-layer acting as a drug reservoir, contributed to this improvement. Biocompatibility assessments, antibacterial activity analysis, blood compatibility tests, and post-diffusion tissue integrity evaluations confirmed the promising biocompatibility of the optimized membranes. Moreover, long-term performance evaluations involving ten repeated usages underscored the reusability of the optimized membrane, highlighting its potential for sustained and reliable drug delivery applications.


Assuntos
Antibacterianos , Sistemas de Liberação de Medicamentos , Membranas Artificiais , Polímeros , Dióxido de Silício , Antibacterianos/administração & dosagem , Antibacterianos/farmacologia , Antibacterianos/química , Dióxido de Silício/química , Polímeros/química , Porosidade , Sulfonas/química , Sulfonas/administração & dosagem , Liberação Controlada de Fármacos , Animais , Azitromicina/administração & dosagem , Azitromicina/farmacocinética , Azitromicina/química , Azitromicina/farmacologia , Humanos
4.
Cell Mol Biol (Noisy-le-grand) ; 70(5): 100-110, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38814229

RESUMO

Molecularly imprinted polymers (MIPs) are pivotal in medicine, mimicking biological receptors with enhanced specificity and affinity. Comprising templates, functional monomers, and cross-linkers, MIPs form stable three-dimensional polymer networks. Synthetic templates like glycan and aptamers improve efficiency, guiding the molecular imprinting process. Cross-linking determines MIPs' morphology and mechanical stability, with printable hydrogels offering biocompatibility and customizable properties, mimicking native extracellular matrix (ECM) microenvironments. Their versatility finds applications in tissue engineering, soft robotics, regenerative medicine, and wastewater treatment. In cancer research, MIPs excel in both detection and therapy. MIP-based detection systems exhibit superior sensitivity and selectivity for cancer biomarkers. They target nucleic acids, proteins, and exosomes, providing stability, sensitivity, and adaptability. In therapy, MIPs offer solutions to challenges like multidrug resistance, excelling in drug delivery, photodynamic therapy, photothermal therapy, and biological activity regulation. In microbiology, MIPs serve as adsorbents in solid-phase extraction (SPE), efficiently separating and enriching antibiotics during sample preparation. They contribute to bacterial identification, selectively capturing specific strains or species. MIPs aid in detecting antibiotic residues using fluorescent nanostructures and developing sensors for sulfadiazine detection in food samples. In summary, MIPs play a pivotal role in advancing medical technologies with enhanced sensitivity, selectivity, and versatility. Applications range from biomarker detection to innovative cancer therapies, making MIPs indispensable for the accurate determination and monitoring of diverse biological and environmental samples.


Assuntos
Antibacterianos , Polímeros Molecularmente Impressos , Neoplasias , Humanos , Polímeros Molecularmente Impressos/química , Neoplasias/diagnóstico , Antibacterianos/análise , Medicina de Precisão/métodos , Impressão Molecular/métodos , Biomarcadores Tumorais
5.
Spectrochim Acta A Mol Biomol Spectrosc ; 313: 124057, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38457872

RESUMO

A simple, highly sensitive, and selective fluorometric aptasensing platform based on aptamer and graphene oxide (GO) is proposed for the determination of mercury (II) ion (Hg2+). In the designed assay, two aptamer probes, a carboxy-fluorescein (FAM) labeled aptamer (aptamer A) and its complementary (aptamer B) with partial complement containing several mismatches and GO as the quencher were used. In the absence of Hg2+, both A and B aptamers were adsorbed on the surface of GO by π-π-stacking, leading to fluorescence quenching of FAM due to fluorescence resonance energy transfer (FRET). Upon exposure to Hg2+, the A and B aptamer strands bind Hg2+ and form T-Hg2+-T complexes, leading to the formation of a stable double-stranded aptamer. The double-stranded aptamer is detached from the GO surface, resulting in the recovery of FAM fluorescence. The fluorescence intensity (FI) of the developed sensor was correlated with the Hg2+ concentration under optimized experimental conditions in two wide linear ranges, even in the presence of 10 divalent cations as interferences. The linear ranges were obtained from 200.0 to 900.0 fM and 5.0 to 33.0 pM, a limit of detection (LOD) of 106.0 fM, and a limit of quantification (LOQ) of 321.3 fM. The concentration of Hg2+ was determined in five real samples containing three water and two serum samples, using spiking and standard addition methods and the results were compared with the spiked amounts and atomic absorption (AAS) as standard method respectively, with acceptable recoveries. Furthermore, in the standard addition method, to overcome the effects of matrix influence of real samples in quantitative predictions, the excitation-emission matrix (EEM) data for samples was simultaneously analyzed by multivariate curve resolution with alternating least squares (MCR-ALS) as a second-order standard addition method (SOSAM).


Assuntos
Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , Grafite , Mercúrio , Transferência Ressonante de Energia de Fluorescência/métodos , Fluorometria/métodos , Água , Limite de Detecção , Oligonucleotídeos , Técnicas Biossensoriais/métodos , Aptâmeros de Nucleotídeos/metabolismo
6.
Polymers (Basel) ; 16(4)2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38399888

RESUMO

Efficient drug delivery remains a critical challenge for treating neurodegenerative diseases, such as Alzheimer's disease (AD). Using innovative nanomaterials, delivering current medications like acetylcholinesterase inhibitors to the brain through the intranasal route is a promising strategy for managing AD. Here, we developed a unique combinational drug delivery system based on N,N,N-trimethyl chitosan nanoparticles (NPs). These NPs encapsulate rivastigmine, the most potent acetylcholinesterase inhibitor, along with insulin, a complementary therapeutic agent. The spherical NPs exhibited a zeta potential of 17.6 mV, a size of 187.00 nm, and a polydispersity index (PDI) of 0.29. Our findings demonstrate significantly improved drug transport efficiency through sheep nasal mucosa using the NPs compared to drug solutions. The NPs exhibited transport efficiencies of 73.3% for rivastigmine and 96.9% for insulin, surpassing the efficiencies of the drug solutions, which showed transport efficiencies of 52% for rivastigmine and 21% for insulin ex vivo. These results highlight the potential of a new drug delivery system as a promising approach for enhancing nasal transport efficiency. These combinational mucoadhesive NPs offer a novel strategy for the simultaneous cerebral delivery of rivastigmine and insulin, which could prove helpful in developing effective treatments of AD and other neurodegenerative conditions.

7.
J Biomol Struct Dyn ; : 1-11, 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38263739

RESUMO

One approach to accelerate the availability of new cancer drugs is to test drugs approved for other conditions as anticancer agents. During recent decades, penciclovir (PNV) has been frequently utilized as a potent antiviral drug, in particular against infections caused by herpes viruses. Many antivirals interact with DNA and change their expression level, so determining the binding mode is of great importance. In our laboratory, we have focused our attention to design improved drugs that target cellular DNA, to understand the mechanism of action at the molecular level, and also to investigate the effect of antiviral drugs as anticancer agents. The results of ct-DNA-PNV interactions at physiological pH using fluorescence spectroscopy, UV-visible absorption spectroscopy, and molecular modeling reveal this drug binds well to ct-DNA through groove binding. The circular dichroism measurements displayed that PNV caused a slight change in the DNA structure which affirmed that the binding of PNV with the DNA occurs through the groove mode. Besides, multi-spectroscopic and molecular docking were used to evaluate how PNV interacts with human serum albumin under physiological conditions. The findings of fluorescence quenching suggested that static quenching was involved in the spontaneous development of HSA-PNV complex through hydrophobic force. The docking simulation results validated the findings of spectroscopic techniques.Communicated by Ramaswamy H. Sarma.

8.
Biotechnol Appl Biochem ; 71(2): 272-279, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38054266

RESUMO

Obesity has been linked to a low-grade inflammatory process in the white adipose tissue. Our study aims to detect the relationship between cytokine levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and C-reactive protein (CRP) in obese diabetics, compared to obese non-diabetics, Iraqi individuals. Ninety Iraqi adults, 45 type 2 diabetic and 45 non-diabetic obese, were selected as controls. Serum levels of TNF-α, IL-6, CRP, homeostatic model assessment for homeostasis model assessment of insulin resistance (HOMA-IR), body fat, and body mass index (BMI) were measured. The concentration of TNF-α, IL-6, and CRP were significantly greater in the obese diabetics, compared to the obese non-diabetics. BMI was significantly positively correlated with the concentration of TNF-α, IL-6, and CRP in the two groups. At the same time, HOMA-IR was non-significantly positively associated with them in obese diabetics. In contrast, the correlation was significantly positive between HOMA-IR with TNF-a, IL-6, and CRP in the obese non-diabetics group. Obese diabetics have more inflammation than obese non-diabetics as evidenced by the former's higher levels of TNF-α and IL-6. Obesity-related imbalances disrupt metabolic processes and increase CRP, TNF-, and IL-6 levels. Therefore, IR is promoted by the increase of cytokines.


Assuntos
Diabetes Mellitus , Resistência à Insulina , Adulto , Humanos , Proteína C-Reativa/metabolismo , Interleucina-6 , Fator de Necrose Tumoral alfa/metabolismo , Citocinas , Obesidade/complicações , Obesidade/metabolismo
9.
Front Pharmacol ; 14: 1227423, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37701036

RESUMO

Intranasal administration is a drug delivery approach to provide a non-invasive pharmacological response in the central nervous system with relatively small peripheral side effects. To improve the residence time of intranasal drug delivery systems in the nasal mucosa, mucoadhesive polymers (e.g., chitosan) can be used. Here, insulin-loaded chitosan nanoparticles were synthesized and their physiochemical properties were evaluated based on requirements of intranasal administration. The nanoparticles were spherical (a hydrodynamic diameter of 165.3 nm, polydispersity index of 0.24, and zeta potential of +21.6 mV) that granted mucoadhesion without any noticeable toxicity to the nasal tissue. We applied a new approach using the Krebs-Henseleit buffer solution along with simulated nasal fluid in a Franz's diffusion cell to study this intranasal drug delivery system. We used the Krebs-Henseleit buffer because of its ability to supply glucose to the cells which serves as a novel ex vivo diffusion medium to maintain the viability of the tissue during the experiment. Based on diffusion rate and histopathological endpoints, the Krebs-Henseleit buffer solution can be a substituent solution to the commonly used simulated nasal fluid for such drug delivery systems.

10.
Biosensors (Basel) ; 13(9)2023 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-37754072

RESUMO

Lateral flow tests are one of the most important types of paper-based point-of-care (POCT) diagnostic tools. It shows great potential as an implement for improving the rapid screening and management of infections in global pandemics or other potential health disorders by using minimally expert staff in locations where no sophisticated laboratory services are accessible. They can detect different types of biomarkers in various biological samples and provide the results in a little time at a low price. An important challenge regarding conventional LFAs is increasing their sensitivity and specificity. There are two main approaches to increase sensitivity and specificity, including assay improvement and target enrichment. Assay improvement comprises the assay optimization and signal amplification techniques. In this study, a summarize of various sensitivity and specificity enhancement strategies with an objective evaluation are presented, such as detection element immobilization, capillary flow rate adjusting, label evolution, sample extraction and enrichment, etc. and also the key findings in improving the LFA performance and solving their limitations are discussed along with numerous examples.


Assuntos
Bioensaio , Sistemas Automatizados de Assistência Junto ao Leito , Humanos , Sensibilidade e Especificidade , Técnicas de Amplificação de Ácido Nucleico , Pandemias
11.
Biosensors (Basel) ; 13(6)2023 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-37366984

RESUMO

Controlling water and food contamination by pathogenic organisms requires quick, simple, and low-cost methods. Using the affinity between mannose and type I fimbriae in the cell wall of Escherichia coli (E. coli) bacteria as evaluation elements compared to the conventional plate counting technique enables a reliable sensing platform for the detection of bacteria. In this study, a simple new sensor was developed based on electrochemical impedance spectroscopy (EIS) for rapid and sensitive detection of E. coli. The biorecogniton layer of the sensor was formed by covalent attachment of p-carboxyphenylamino mannose (PCAM) to gold nanoparticles (AuNPs) electrodeposited on the surface of a glassy carbon electrode (GCE). The resultant structure of PCAM was characterized and confirmed using a Fourier Transform Infrared Spectrometer (FTIR). The developed biosensor demonstrated a linear response with a logarithm of bacterial concentration (R2 = 0.998) in the range of 1.3 × 10 1~1.3 × 106 CFU·mL-1 with the limit of detection of 2 CFU·mL-1 within 60 min. The sensor did not generate any significant signals with two non-target strains, demonstrating the high selectivity of the developed biorecognition chemistry. The selectivity of the sensor and its applicability to analysis of the real samples were investigated in tap water and low-fat milk samples. Overall, the developed sensor showed to be promising for the detection of E. coli pathogens in water and low-fat milk due to its high sensitivity, short detection time, low cost, high specificity, and user-friendliness.


Assuntos
Técnicas Biossensoriais , Nanopartículas Metálicas , Escherichia coli/química , Carbono/química , Manose , Ouro/química , Nanopartículas Metálicas/química , Técnicas Biossensoriais/métodos , Eletrodos , Água , Técnicas Eletroquímicas/métodos , Limite de Detecção
12.
Spectrochim Acta A Mol Biomol Spectrosc ; 293: 122448, 2023 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-36773423

RESUMO

Mercury is a highly toxic and potentially bioaccumulative heavy metal ion that can cause severe health problems in humans even at very low concentrations. Thus, the development of a simple, rapid, and sensitive assay for the effective detection of mercury ions at trace levels is of great importance. Here, nitrogen and sulfur co-doped carbon quantum dots (N,S-CQD) were synthesized by a simple hydrothermal treatment of chitosan in the presence of thiourea and citric acid with a quantum yield (QY) up to 33.0 % and used as a selective fluorescent probe to detect mercury ions (Hg2+). The effect of pH, ionic strength, and time on the fluorescence intensity of N,S-CQD were investigated and optimized. The synthesized N,S-CQD showed ultrasensitive ability to detect Hg2+ ions in the water samples, also in the presence of 11 interfering metal ions, with a low detection limit (∼4 nM) over a wide linear range from ∼5-160 nM. The sensing performance of N,S-CQD probe in real sample applications was evaluated by the detection of Hg2+ in lake water samples, which confirmed its potential application in environmental analysis.

13.
Front Aging Neurosci ; 14: 968039, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36046494

RESUMO

Statins are a class of widely prescribed drugs used to reduce low-density lipoprotein cholesterol (LDL-C) and important to prevent cardiovascular diseases (CVD). Most statin users are older adults with CVD, who are also at high risk of cognitive decline. It has been suggested that statins can alter cognitive performance, although their positive or negative effects are still debated. With more than 200 million people on statin therapy worldwide, it is crucial to understand the reasons behind discrepancies in the results of these studies. Here, we review the effects of statins on cognitive function and their association with different etiologies of dementia, and particularly, Alzheimer's disease (AD). First, we summarized the main individual and statin-related factors that could modify the cognitive effects of statins. Second, we proposed the underlying mechanisms for the protective and adverse effects of statins on cognitive performance. Finally, we discussed potential causes of discrepancies between studies and suggested approaches to improve future studies assessing the impact of statins on dementia risk and cognitive function.

14.
Sci Rep ; 12(1): 3299, 2022 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-35228597

RESUMO

Evaluation of extracellular domain of human epidermal growth factor receptor-2 (HER2-ECD) oncomarker status is an impressive factor in screening, diagnosing and monitoring early-stage breast cancer (BC). Electrochemical aptamer-based nanobiosensor with high sensitivity and selectivity for quantitative and qualitative measurement of HER2-ECD oncomarker was developed. In this study, the nanocomposite made by distinct materials included reduced graphene oxide nano-sheets (rGONs) and rhodium nanoparticles (Rh-NPs) on the graphite electrode (GE) surface. This structure resulted in amplified electrochemical activity, high surface area, stability, and bio-compatibility. Each of the steps of preparing nanomaterials and setting up biosensor were carefully examined by analytical and electrochemical techniques. Various modified electrodes were constructed and analyzed in terms of electrochemical performance, morphology, size, and shape of nanomaterials. The GE-based aptasensor had a noteworthy and conducive results against HER2-ECD with a wide dynamic range of 10.0-500.0 ng/mL, a low limit of detection (LOD) of 0.667 ng/mL (significantly less than the clinical cut-off), and a low limit of quantification (LOQ) of 2.01 ng/mL. The benefits provided by this aptasensor such as broad dynamic range, high sensitivity, selectivity, stability, reproducibility, and low cost suggest tremendous potential for non-invasive detection and monitoring of the HER2-ECD levels of BC care and clinical diagnosis.


Assuntos
Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , Grafite , Nanopartículas Metálicas , Ródio , Aptâmeros de Nucleotídeos/química , Técnicas Biossensoriais/métodos , Técnicas Eletroquímicas/métodos , Eletrodos , Ouro/química , Grafite/química , Humanos , Limite de Detecção , Biópsia Líquida , Nanopartículas Metálicas/química , Reprodutibilidade dos Testes
15.
J Drug Target ; 30(3): 233-243, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34415800

RESUMO

As a non-invasive method of local and systemic drug delivery, the administration of active pharmaceutical ingredients (APIs) via the pulmonary route represents an ideal approach for the therapeutic treatment of pulmonary diseases. The pulmonary route provides a number of advantages, including the rapid absorption which results from a high level of vascularisation over a large surface area and the successful avoidance of first-pass metabolism. Aerosolization of nanoparticles (NPs) is presently under extensive investigation and exhibits a high potential for targeted delivery of therapeutic agents for the treatment of a wide range of diseases. NPs need to possess specific characteristics to facilitate their transport along the pulmonary tract and appropriately overcome the barriers presented by the pulmonary system. The most challenging aspect of delivering NP-based drugs via the pulmonary route is developing colloidal systems with the optimal physicochemical parameters for inhalation. The physiochemical properties of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) have been investigated as a template for the synthesis of NPs to assist in the formulation of virus-like particles (VLPs) for pharmaceutical delivery, vaccine production and diagnosis assays.


Assuntos
Antivirais/administração & dosagem , Antivirais/uso terapêutico , Tratamento Farmacológico da COVID-19 , Nanopartículas/administração & dosagem , SARS-CoV-2 , Administração por Inalação , Humanos , Farmacologia em Rede
16.
Pharmaceuticals (Basel) ; 14(11)2021 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-34832918

RESUMO

There is no definite cure for Alzheimer's disease (AD) due to its multifactorial origin. Drugs that inhibit acetylcholinesterase (AChE), such as rivastigmine, are promising symptomatic treatments for AD. Emerging evidence suggests that insulin therapy can hinder several aspects of AD pathology. Insulin has been shown to modify the activity of AChE, but it is still unknown how insulin and AChE interact. Combination therapy, which targets several features of the disease based on existing medications, can provide a worthy therapy option for AD management. However, to date, no studies have examined the potential interaction of insulin with AChE and/or rivastigmine in vitro. In the present study, we employed the Response Surface Methodology (RSM) as an in vitro assessment to investigate the effect of insulin on both AChE activity and rivastigmine inhibitory action using a common spectrophotometric assay for cholinesterase activity, Ellman's method. Our results showed that insulin, even at high concentrations, has an insignificant effect on both the activity of AChE and rivastigmine's inhibitory action. The variance of our data is near zero, which means that the dispersion is negligible. However, to improve our understanding of the possible interaction of insulin and rivastigmine, or its target AChE, more in silico modelling and in vivo studies are needed.

17.
Eur J Pharm Sci ; 167: 106040, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34655736

RESUMO

Integrating nanoparticles (NPs) as a smart and targeted tool for drug delivery with dissolving microneedle (DMN) patch, the non-invasive device for drug delivery, is a promising for future therapeutic delivery applications. Liraglutide (Lira) encapsulation in poly (lactic-co-glycolic acid) (PLGA) NPs provides a sustained release of Lira to 15 days in a biphasic profile which 80% of released content happens in the first 8 days. Embedding such sustained release NPs in the DMN comprising poly vinyl pyrrolidone (PVP) 50% w/v, eliminates the need for Lira subcutaneous injection. Additionally, NPs containing DMN enhance mechanical strength of needles to 5.31 N compared to DMN with pure Lira content which was 4.32 N. The flexible backing layer of the DMN was obtained via blending of PVP and poly vinyl alcohol (PVA) in 10% w/v. Circular dichroism (CD) analysis showed that Lira encapsulated in NPs maintained its native secondary structure even after solidification in DMN. In this study, the capacity of 2 kinds of 500 µm and 1000 µm needles to deliver the desired dose of drug was obtained based on experimental and mathematical methods.


Assuntos
Diabetes Mellitus Tipo 2 , Agulhas , Diabetes Mellitus Tipo 2/tratamento farmacológico , Portadores de Fármacos , Humanos , Liraglutida , Obesidade
18.
Reprod Sci ; 28(12): 3361-3379, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34231166

RESUMO

The use of exogenous antioxidants or the combination of them during in vitro oocyte/embryo culture media is reasonable. Co-delivery by nanocarrier has been designed to overcome the limitations of combining them traditionally. In this work, amphiphilic chitosan nanocarrier (ACN) was applied to co-encapsulate melatonin (Mel) and tretinoin (TTN) by the self-assembled method and evaluate their synergistic antioxidant efficacy in mice oocytes/embryos. The formation of single/dual-ACN was confirmed by Fourier-transformed infrared spectroscopy (FT-IR). The average particle diameter, size distribution, polydispersity index (PDI), and zeta potential of them were measured by dynamic light scattering (DLS), and the morphology was evaluated by TEM and SEM technologies. Also, the encapsulation efficiency (EE%) and drug loading content (DL%) of the nanocapsules were determined by UV-vis spectrophotometry. Studies of the in vitro release showed a continued drug release without any bursting effect of Mel+TTN-ACNs compared with single Mel/TTN-ACNs. Then, in both experiments, nuclear staining (Aceto-orcein and Hoechst 33342), fluorescent staining of H2DCFDA, chemiluminescence test, and qRT-PCR technique were performed as in vitro toxicity studies. The results of all these evaluations demonstrated that the dual delivery of Mel and TTN could accumulate a safety (without high-dose toxicity) synergistic anti-oxidative effect in oocyte/embryo by passive controlled, and inhibit intra/extracellular ROS levels by an enhanced intracellular penetration.


Assuntos
Antioxidantes/administração & dosagem , Quitosana/administração & dosagem , Melatonina/administração & dosagem , Mórula/efeitos dos fármacos , Nanocápsulas/administração & dosagem , Oócitos/efeitos dos fármacos , Tretinoína/administração & dosagem , Animais , Antioxidantes/metabolismo , Quitosana/metabolismo , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/metabolismo , Sinergismo Farmacológico , Técnicas de Cultura Embrionária/métodos , Desenvolvimento Embrionário/efeitos dos fármacos , Desenvolvimento Embrionário/fisiologia , Feminino , Masculino , Melatonina/metabolismo , Camundongos , Mórula/metabolismo , Oócitos/metabolismo , Tretinoína/metabolismo
19.
Pharm Dev Technol ; 26(6): 673-681, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33896342

RESUMO

Various nano-sized protein and lipid complexes are being investigated as drug delivery systems. The encapsulation of more than one drug in a single nanocomplex carrier could enhance the therapeutic potency and afford synergistic therapeutic effects. In this study, we developed a novel protein-lipid nanocomplex as a controlled drug delivery system for two important cancer drugs, doxorubicin (DOX) and mitoxantrone (MTO). Apoferritin (AFr) functionalized with folic acid (FA) was used to encapsulate DOX to create the targeted protein nanocomplexes (TPNs). The second drug, MTO, was loaded into the cationic solid lipid nanoparticles (cSLN) to form the liposomal drug nanocomplex particles (MTO-cSLNs). Two complexes were then assembled by tight coupling through ionic interactions to obtain the final drug delivery system, the dual-targeted protein-lipid nanocomplexes (DTPLNs). UV-Vis and fluorescence spectroscopy were used for structural characterization of TPNs and DTPLNs. Transmission electron microscopy (TEM) was used for comprehensive analysis of the final DTPLNs. We confirmed that the DTPLNs display desired time-dependent and pH-dependent drug release behaviors. We also demonstrated the improved anti-cancer efficacy of DOX and MTO in their encapsulated DTPLNs as compared to their free forms. Our results provide promising prospects for the application of the DTPLNs as efficient drug delivery systems.


Assuntos
Antineoplásicos/química , Apoferritinas/química , Doxorrubicina/análogos & derivados , Sistemas de Liberação de Medicamentos/métodos , Ácido Fólico/química , Lipossomos/química , Nanopartículas/química , Neoplasias , Antineoplásicos/administração & dosagem , Antineoplásicos/metabolismo , Apoferritinas/administração & dosagem , Apoferritinas/metabolismo , Cátions , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Relação Dose-Resposta a Droga , Doxorrubicina/administração & dosagem , Doxorrubicina/química , Doxorrubicina/metabolismo , Ácido Fólico/administração & dosagem , Ácido Fólico/metabolismo , Humanos , Lipossomos/administração & dosagem , Lipossomos/metabolismo , Células MCF-7 , Nanopartículas/administração & dosagem , Nanopartículas/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo
20.
Artigo em Inglês | MEDLINE | ID: mdl-33455539

RESUMO

In this work the binding of artificial sweetener aspartame with human serum albumin (HSA) was studied at physiological pH. Binding studies of aspartame (APM) with HSA are useful to understand APM -HSA interaction, mechanism and providing guidance for the application and design of new and more efficient artificial sweeteners. The interaction was investigated by spectrophotometric, spectrofluorometric competition experiment and circular dichroism (CD) techniques. The results indicated that the binding of APM to HSA caused fluorescence quenching of HSA through static quenching mechanism with binding constant 1.42 × 10+4 M-1 at 298 K and the number of binding sites is approximately one. Thermodynamic parameters, enthalpy changes (ΔH) and entropy changes (ΔS) were calculated to be -41.20 kJ mol-1 and -58.19 J mol-1 K-1, respectively, according to van't Hoff equation, which indicated that reaction is enthalpically driven. Quenching of the fluorescence of HSA was found to be a static quenching process. The binding constants and number of binding sites were obtained at three different temperatures (298, 308 and 318 K). Combining above results and those of spectrofluorometric competition experiment and circular dichroism (CD), indicated that APM binds to HSA via Sudlow's site I. Furthermore, the study of molecular docking on HSA binding also indicated that APM can strongly bind to the site I (subdomain IIA) of HSA mainly by hydrophobic interaction and hydrogen bond interactions exist between APM and HSA.


Assuntos
Aspartame/metabolismo , Albumina Sérica Humana/metabolismo , Análise Espectral , Ligação Competitiva , Humanos , Modelos Moleculares , Ligação Proteica , Conformação Proteica , Albumina Sérica Humana/química
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