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1.
Curr Rheumatol Rev ; 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38584559

RESUMO

BACKGROUND: Osteoarthritis (OA) is becoming a major medical burden worldwide due to changing lifestyles and aging populations. Osteoarthritis is a disease characterized by a variety of anatomic and physiological changes to joints, including cartilage degradation, bone remodeling, and the formation of osteophytes. These changes cause pain, stiffness, swelling, and limitations in joint function. Glucosamine serves as a fundamental constituent for cartilage, the resilient connective tissue responsible for cushioning joints. Glucosamine Sulphate Potassium Chloride (GSPC) supplementation is widely employed to mitigate symptoms linked to osteoarthritis, a degenerative joint disorder hallmarked by cartilage degradation. AIM: Palliative care aims at minimizing pain and disability and improving function, performance, and quality of life. In this study, the emulgel formulation of GSPC was developed and checked for its potential. OBJECTIVE: Currently, OA does not have a definitive treatment. Since conventional dosage forms cannot deliver the active drug content at a predefined target site in a predictable manner throughout the treatment period, a new carrier system is always required. Considering their reduced size, targeting potential, and site specificity, nanocarrier-based approaches could hold an answer to shortcomings associated with conventional routes. Thus, the objective of the current study was to formulate and characterize glucosamine sulphate potassium chloride-loaded emulgel for the treatment of osteoarthritis. METHODS: Microemulsion of glucosamine sulphate potassium chloride was formulated using a spontaneous emulsification method comprising of oleic acid (oil phase), Tween 80, Tween 20 (surfactant) and PEG 400, Span 80 (co-surfactant), and distilled water (aqueous phase). The microemulsions were evaluated for surface morphology, globule size, poly-dispersibility index (PDI), zeta potential, and viscosity, and the final batch of microemulsions was selected. RESULT: The optimized microemulsion contained 35% co-surfactant (propylene glycol), 20% surfactant (Tween 20), and 15% oil (oleic acid) and glucosamine sulphate potassium chloride in a dose of 60 mg, which has sufficient drug loading capacity with a droplet size of 182 nm for optimized formulation. The optimized microemulsion formulation was added to gel prepared by Carbopol 934 in a 1:1 (w/w) ratio, leading to the formulation of glucosamine sulphate potassium chloride- containing emulgel. The prepared emulgel was further evaluated for viscosity, drug content, pH, and in-vitro drug release. Emulgel formulation (F6) showed 88% drug release after 6 hours, and it followed the Higuchi model. CONCLUSION: Glucosamine Sulphate Potassium Chloride (GSPC) is used in the treatment of OA by increasing the production of proteoglycans, which can cause the cartilage to break down. Emulgel formulation (F3) showed 75.41% drug release, and formulation (F6) showed 88% drug release after 6 h. Therefore, it may be concluded that an emulgel of GSPC can be used as a controlled-release dosage form of the drug for local application in OA.

2.
Arch Microbiol ; 206(4): 134, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38433145

RESUMO

Acanthamoeba castellanii are opportunistic pathogens known to cause infection of the central nervous system termed: granulomatous amoebic encephalitis, that mostly effects immunocompromised individuals, and a sight threatening keratitis, known as Acanthamoeba keratitis, which mostly affects contact lens wearers. The current treatment available is problematic, and is toxic. Herein, an amphiphilic star polymer with AB2 miktoarms [A = hydrophobic poly(ℇ-Caprolacton) and B = hydrophilic poly (ethylene glycol)] was synthesized by ring opening polymerization and CuI catalyzed azide-alkyne cycloaddition. Characterization by 1H and 13C NMR spectroscopy, size-exclusion chromatography and fluorescence spectroscopy was accomplished. The hydrophobic drug itraconazole (ITZ) was incorporated in self-assembled micellar structure of AB2 miktoarms through co-solvent evaporation. The properties of ITZ loaded (ITZ-PCL-PEG2) and blank micelles (PCL-PEG2) were investigated through zeta sizer, scanning electron microscopy and Fourier-transform infrared spectroscopy. Itraconazole alone (ITZ), polymer (DPB-PCL), empty polymeric micelles (PCL-PEG2) alone, and itraconazole loaded in polymeric micelles (ITZ-PCL-PEG2) were tested for anti-amoebic potential against Acanthamoeba, and the cytotoxicity on human cells were determined. The polymer was able to self-assemble in aqueous conditions and exhibited low value for critical micelle concentration (CMC) 0.05-0.06 µg/mL. The maximum entrapment efficiency of ITZ was 68%. Of note, ITZ, DPB, PCL-PEG2 and ITZ-PCL-PEG2 inhibited amoebae trophozoites by 37.34%, 36.30%, 35.77%, and 68.24%, respectively, as compared to controls. Moreover, ITZ-PCL-PEG2 revealed limited cytotoxicity against human keratinocyte cells. These results are indicative that ITZ-PCL-PEG2 micelle show significantly better anti-amoebic effects as compared to ITZ alone and thus should be investigated further in vivo to determine its clinical potential.


Assuntos
Acanthamoeba castellanii , Micelas , Humanos , Itraconazol/farmacologia , Alcinos , Polímeros
3.
Methods Mol Biol ; 2674: 55-60, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37258959

RESUMO

Bacterial extracellular vesicles (EVs) contain numerous active substances that mediate bacterial interactions with their host and with other microbes. Best defined are the EVs from Gram-negative bacteria that have been shown to deliver virulence factors, modulate the immune responses, mediate antibiotic resistance, and also inhibit competitive microbes. Due to the complex cell wall structures of Gram-positive bacteria and mycobacteria, EVs from these bacteria were only recently reported. This protocol describes the isolation of EVs from mycobacteria.


Assuntos
Vesículas Extracelulares , Mycobacterium , Mycobacterium/fisiologia , Bactérias Gram-Positivas , Fatores de Virulência/análise , Vesículas Extracelulares/química
4.
Pharmaceutics ; 15(2)2023 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-36839864

RESUMO

Multidrug-resistant tuberculosis (MDR) continues to pose a threat to public health. Previously, we identified a cationic host defense peptide with activity against Mycobacterium tuberculosis in vivo and with a bactericidal effect against MDR M. tuberculosis at therapeutic concentrations. To understand the mechanisms of this peptide, we investigated its interactions with live M. tuberculosis and liposomes as a model. Peptide interactions with M. tuberculosis inner membranes induced tube-shaped membranous structures and massive vesicle formation, thus leading to bubbling cell death and ghost cell formation. Liposomal studies revealed that peptide insertion into inner membranes induced changes in the peptides' secondary structure and that the membranes were pulled such that they aggregated without permeabilization, suggesting that the peptide has a strong inner membrane affinity. Finally, the peptide targeted essential proteins in M. tuberculosis, such as 60 kDa chaperonins and elongation factor Tu, that are involved in mycolic acid synthesis and protein folding, which had an impact on bacterial proliferation. The observed multifaceted targeting provides additional support for the therapeutic potential of this peptide.

5.
Curr Drug Saf ; 18(4): 465-473, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36056846

RESUMO

BACKGROUND: Marijuana, also known as cannabis, is the second most widely used illegal psychoactive substance smoked worldwide after tobacco, mainly due to the psychoactive effects induced by D-9-tetrahydrocannabinol (9-THC). Cannabidiol (CBD) is extracted from cannabis and may be used as an anti-inflammatory agent. Some patents on cannabidiol are discussed in this review. The cannabinoid is a non-psychoactive isomer of the more infamous tetrahydrocannabinol (THC); and is available in several administration modes, most known as CBD oil. OBJECTIVES: This study aims to provide an enhanced review of cannabidiol properties used in treating inflammation. This review also emphasises the current safety profile of cannabidiol. METHODS: Cannabis is also called Marijuana. It is the second most commonly used illegal psychoactive substance in the universe after tobacco. D-9-tetrahydrocannabinol (9-THC) present in cannabis produces psychoactive effects. Cannabidiol (CBD) extracted from cannabis is used for antiinflammatory purposes. Cannabis smoking causes various types of cancer, such as lung, tongue, and jaw. The current review took literature from Google Scholar, PubMed, and Google Patents. Many clinical investigations are included in this review. RESULT: After analysing the literature on cannabis, it has been suggested that although cannabis is banned in some countries, it may be included in the treatment and mitigation of some diseases and symptoms like pain management, epilepsy, cancer, and anxiety disorder. Mild side effects were frequently observed in cannabis medications, which included infertility in females, liver damage, etc. Conclusion: Cannabis contains chemical compounds such as the cannabinoids delta-9- tetrahydrocannabinol (THC), a psychoactive substance, and non-psychoactive cannabidiol (CBD). Cannabidiol has been confirmed as an efficient treatment of epilepsy in several clinical trials, with one pure CBD product named Epidiolex. It is also used in treating anxiety and acne, as a pain reliever, and has anti-inflammatory properties.


Assuntos
Canabidiol , Canabinoides , Cannabis , Epilepsia , Feminino , Humanos , Canabidiol/efeitos adversos , Dronabinol/efeitos adversos , Dronabinol/análise , Epilepsia/tratamento farmacológico
6.
Elife ; 102021 12 24.
Artigo em Inglês | MEDLINE | ID: mdl-34951590

RESUMO

Transition metals, such as zinc, are essential micronutrients in all organisms, but also highly toxic in excessive amounts. Heavy-metal transporting P-type (PIB) ATPases are crucial for homeostasis, conferring cellular detoxification and redistribution through transport of these ions across cellular membranes. No structural information is available for the PIB-4-ATPases, the subclass with the broadest cargo scope, and hence even their topology remains elusive. Here, we present structures and complementary functional analyses of an archetypal PIB-4-ATPase, sCoaT from Sulfitobacter sp. NAS14-1. The data disclose the architecture, devoid of classical so-called heavy-metal-binding domains (HMBDs), and provide fundamentally new insights into the mechanism and diversity of heavy-metal transporters. We reveal several novel P-type ATPase features, including a dual role in heavy-metal release and as an internal counter ion of an invariant histidine. We also establish that the turnover of PIB-ATPases is potassium independent, contrasting to many other P-type ATPases. Combined with new inhibitory compounds, our results open up for efforts in for example drug discovery, since PIB-4-ATPases function as virulence factors in many pathogens.


Heavy metals such as zinc and cobalt are toxic at high levels, yet most organisms need tiny amounts for their cells to work properly. As a result, proteins studded through the cell membrane act as gatekeepers to finetune import and export. These proteins are central to health and disease; their defect can lead to fatal illnesses in humans, and they also help bacteria infect other organisms. Despite their importance, little is known about some of these metal-export proteins. This is particularly the case for PIB-4-ATPases, a subclass found in plants and bacteria and which includes, for example, a metal transporter required for bacteria to cause tuberculosis. Intricate knowledge of the three-dimensional structure of these proteins would help to understand how they select metals, shuttle the compounds in and out of cells, and are controlled by other cellular processes. To reveal this three-dimensional organisation, Grønberg et al. used X-ray diffraction, where high-energy radiation is passed through crystals of protein to reveal the positions of atoms. They focused on a type of PIB-4-ATPases found in bacteria as an example. The work showed that the protein does not contain the metal-binding regions seen in other classes of metal exporters; however, it sports unique features that are crucial for metal transport such as an adapted pathway for the transport of zinc and cobalt across the membrane. In addition, Grønberg et al. tested thousands of compounds to see if they could block the activity of the protein, identifying two that could kill bacteria. This better understanding of how PIB-4-ATPases work could help to engineer plants capable of removing heavy metals from contaminated soils, as well as uncover new compounds to be used as antibiotics.


Assuntos
Íons/metabolismo , Metais Pesados/metabolismo , ATPases do Tipo-P/química , ATPases do Tipo-P/metabolismo , Rhodobacteraceae/enzimologia , Sítios de Ligação , Transporte Biológico , Proteínas de Transporte de Cátions/metabolismo , Modelos Moleculares , ATPases do Tipo-P/classificação , Conformação Proteica , Rhodobacteraceae/classificação , Zinco/metabolismo
7.
Chem Phys Lipids ; 239: 105115, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34252425

RESUMO

The increase in antimicrobial resistance has created a crisis that has become top priority for global policy and public health. Antibiotics are constantly being rendered in-effective due to the emergence of bacterial resistance; therefore, novel strategies for improving therapeutic efficacies of existing drugs must be focused. Advancements in nanotechnology have opened up new avenues for enhancing therapeutic efficacy of existing drugs via construction of intelligent and efficient delivery systems. This study reports the synthesis of Dapsone based nonionic surfactant and its utilization as delivery system for Ceftriaxone sodium. The synthesized nonionic surfactant was characterized via mass spectrometry and 1H NMR and IR spectroscopic techniques. The drug loaded vesicles of newly synthesized sulfur based nonionic were formed through thin film hydration method and characterized for drug entrapment efficiency, vesicles size, zeta potential, morphology using UV-vis spectrometry, dynamic light scattering (DLS) and atomic force microscopic (AFM) techniques. The biocompatibility of newly synthesized surfactant was assessed using blood hemolysis and in-vitro cells cytotoxicity. Antibacterial potential of drug loaded vesicles was assessed in gram positive and gram negative bacterial cultures. The spectroscopic results confirm successful synthesis of novel sulfur based nonionic surfactant that formed spherical shaped drug loaded vesicles with an average size of 97.95 ± 3.45 nm and 56.3 ± 3.15 % entrapment of the model drug (Ceftriaxone sodium). The vesicles displayed negative surface charge of -16.8 ± 3.72 mV and released the entrapped drug in a controlled way in-vitro drug release. The drug loaded vesicular formulation showed enhanced cellular uptake and greater antibacterial potentials when compared with control. Results of this study show that the Dapsone based surfactant is safe, biocompatible, non-toxic and can be used as promising vesicular carrier for enhancing therapeutic efficacy of antibacterial drug, Ceftriaxone sodium.


Assuntos
Materiais Biocompatíveis/química , Dapsona/química , Portadores de Fármacos/síntese química , Tensoativos/química , Antibacterianos/química , Antibacterianos/metabolismo , Antibacterianos/farmacologia , Materiais Biocompatíveis/metabolismo , Materiais Biocompatíveis/farmacologia , Biofilmes/efeitos dos fármacos , Dapsona/metabolismo , Dapsona/farmacologia , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/fisiologia , Bactérias Gram-Positivas/efeitos dos fármacos , Bactérias Gram-Positivas/fisiologia , Hemólise/efeitos dos fármacos , Humanos , Micelas , Testes de Sensibilidade Microbiana , Tamanho da Partícula , Enxofre/química
8.
Sci Rep ; 11(1): 4201, 2021 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-33603037

RESUMO

Alternative ways to prevent and treat infectious diseases are needed. Previously, we identified a fungal peptide, NZX, that was comparable to rifampicin in lowering M. tuberculosis load in a murine tuberculosis (TB) infection model. Here we assessed the potential synergy between this cationic host defence peptide (CHDP) and the current TB drugs and analysed its pharmacokinetics. We found additive effect of this peptide with isoniazid and ethambutol and confirmed these results with ethambutol in a murine TB-model. In vivo, the peptide remained stable in circulation and preserved lung structure better than ethambutol alone. Antibiotic resistance studies did not induce mutants with reduced susceptibility to the peptide. We further observed that this peptide was effective against nontuberculous mycobacteria (NTM), such as M. avium and M. abscessus, and several Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus. In conclusion, the presented data supports a role for this CHDP in the treatment of drug resistant organisms.


Assuntos
Antibacterianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/farmacologia , Tuberculose/tratamento farmacológico , Animais , Etambutol/farmacologia , Feminino , Humanos , Isoniazida/farmacologia , Masculino , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Testes de Sensibilidade Microbiana/métodos , Infecções por Mycobacterium não Tuberculosas/dietoterapia , Mycobacterium tuberculosis/efeitos dos fármacos , Micobactérias não Tuberculosas/efeitos dos fármacos , Rifampina/farmacologia , Tuberculose/microbiologia
9.
BMC Microbiol ; 21(1): 51, 2021 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-33596837

RESUMO

BACKGROUNDS: Escherichia coli K1 causes neonatal meningitis. Transcriptome studies are indispensable to comprehend the pathology and biology of these bacteria. Recently, we showed that nanoparticles loaded with Hesperidin are potential novel antibacterial agents against E. coli K1. Here, bacteria were treated with and without Hesperidin conjugated with silver nanoparticles, and silver alone, and 50% minimum inhibitory concentration was determined. Differential gene expression analysis using RNA-seq, was performed using Degust software and a set of genes involved in cell stress response and metabolism were selected for the study. RESULTS: 50% minimum inhibitory concentration with silver-conjugated Hesperidin was achieved with 0.5 µg/ml of Hesperidin conjugated with silver nanoparticles at 1 h. Differential genetic analysis revealed the expression of 122 genes (≥ 2-log FC, P< 0.01) in both E. coli K1 treated with Hesperidin conjugated silver nanoparticles and E. coli K1 treated with silver alone, compared to untreated E. coli K1. Of note, the expression levels of cation efflux genes (cusA and copA) and translocation of ions, across the membrane genes (rsxB) were found to increase 2.6, 3.1, and 3.3- log FC, respectively. Significant regulation was observed for metabolic genes and several genes involved in the coordination of flagella. CONCLUSIONS: The antibacterial mechanism of nanoparticles maybe due to disruption of the cell membrane, oxidative stress, and metabolism in E. coli K1. Further studies will lead to a better understanding of the genetic mechanisms underlying treatment with nanoparticles and identification of much needed novel antimicrobial drug candidates.


Assuntos
Antibacterianos/farmacologia , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , Perfilação da Expressão Gênica , Hesperidina/farmacologia , Nanopartículas Metálicas/química , Prata/farmacologia , Hesperidina/química , Testes de Sensibilidade Microbiana , Estresse Oxidativo/efeitos dos fármacos , Transcriptoma
10.
Pharm Dev Technol ; 26(3): 291-301, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33475034

RESUMO

The current study focuses on the development, characterization, biocompatibility investigation and oral bioavailability evaluation of ceftriaxone (CFT)-loaded lactobionic acid (LBA)-functionalized iron oxide magnetic nanoparticles (MNP-LBA). Atomic force microscopy and dynamic light scattering showed that the developed CFT-loaded MNP-LBA is spherical, with a measured hydrodynamic size of 147 ± 15.9 nm and negative zeta potential values (-35 ± 0.58 mV). Fourier transformed infrared analysis revealed interactions between the nanocarrier and the drug. Nanoparticles showed high drug entrapment efficiencies of 91.5 ± 2.2%, and the drug was released gradually in vitro and shows prolonged in vitro stability using simulated gastrointestinal (GI) fluids. The formulations were found to be highly biocompatible (up to 100 µg/mL) and hemocompatible (up to 1.0 mg/mL). Using an albino rabbit model, the formulation showed a significant enhancement in drug plasma concentration up to 14.46 ± 2.5 µg/mL in comparison with its control (1.96 ± 0.58 µg/mL). Overall, the developed MNP-LBA formulation was found promising for provision of high-drug entrapment, gradual drug release and was appropriate for enhancing the oral delivery of CFT.


Assuntos
Antibacterianos/administração & dosagem , Ceftriaxona/administração & dosagem , Dissacarídeos/química , Portadores de Fármacos/química , Nanopartículas Magnéticas de Óxido de Ferro/química , Administração Oral , Animais , Antibacterianos/sangue , Disponibilidade Biológica , Ceftriaxona/sangue , Coelhos
11.
Sci Rep ; 9(1): 3122, 2019 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-30816269

RESUMO

Herein, we report green synthesized nanoparticles based on stabilization by plant gums, loaded with citrus fruits flavonoids Hesperidin (HDN) and Naringin (NRG) as novel antimicrobial agents against brain-eating amoebae and multi-drug resistant bacteria. Nanoparticles were thoroughly characterized by using zetasizer, zeta potential, atomic force microscopy, ultravoilet-visible and Fourier transform-infrared spectroscopic techniques. The size of these spherical nanoparticles was found to be in the range of 100-225 nm. The antiamoebic effects of these green synthesized Silver and Gold nanoparticles loaded with HDN and NRG were tested against Acanthamoeba castellanii and Naegleria fowleri, while antibacterial effects were evaluated against methicillin-resistant Staphylococcus aureus (MRSA) and neuropathogenic Escherichia coli K1. Amoebicidal assays revealed that HDN loaded Silver nanoparticles stabilized by gum acacia (GA-AgNPs-HDN) quantitatively abolished amoeba viability by 100%, while NRG loaded Gold nanoparticles stabilized by gum tragacanth (GT-AuNPs-NRG) significantly reduced the viability of A. castellanii and N. fowleri at 50 µg per mL. Furthermore, these nanoparticles inhibited the encystation and excystation by more than 85%, as well as GA-AgNPs-HDN only completely obliterated amoeba-mediated host cells cytopathogenicity. Whereas, GA-AgNPs-HDN exhibited significant bactericidal effects against MRSA and E. coli K1 and reduced bacterial-mediated host cells cytotoxicity. Notably, when tested against human cells, these nanoparticles showed minimal (23%) cytotoxicity at even higher concentration of 100 µg per mL as compared to 50 µg per mL used for antimicrobial assays. Hence, these novel nanoparticles formulations hold potential as therapeutic agents against infections caused by brain-eating amoebae, as well as multi-drug resistant bacteria, and recommend a step forward in drug development.


Assuntos
Amebicidas/administração & dosagem , Antibacterianos/administração & dosagem , Flavanonas/administração & dosagem , Hesperidina/administração & dosagem , Nanopartículas/química , Gomas Vegetais/química , Acanthamoeba castellanii/efeitos dos fármacos , Amebíase/tratamento farmacológico , Amebicidas/química , Amebicidas/farmacologia , Antibacterianos/química , Antibacterianos/farmacologia , Citrus/química , Escherichia coli/efeitos dos fármacos , Infecções por Escherichia coli/tratamento farmacológico , Flavanonas/química , Flavanonas/farmacologia , Química Verde , Goma Arábica/química , Hesperidina/química , Hesperidina/farmacologia , Humanos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Infecções Estafilocócicas/tratamento farmacológico
12.
PLoS One ; 14(2): e0212858, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30807612

RESUMO

BACKGROUND: Intracellular delivery of antimicrobial agents by nanoparticles, such as mesoporous silica particles (MSPs), offers an interesting strategy to treat intracellular infections. In tuberculosis (TB), Mycobacterium tuberculosis avoids components of the immune system by residing primarily inside alveolar macrophages, which are the desired target for TB therapy. METHODS AND FINDINGS: We have previously identified a peptide, called NZX, capable of inhibiting both clinical and multi-drug resistant strains of M. tuberculosis at therapeutic concentrations. In this study we analysed the potential of MSPs containing NZX for the treatment of tuberculosis. The MSPs released functional NZX gradually into simulated lung fluid and the peptide filled MSPs were easily taken up by primary macrophages. In an intracellular infection model, the peptide containing particles showed increased mycobacterial killing compared to free peptide. The therapeutic potential of peptide containing MSPs was investigated in a murine infection model, showing that MSPs preserved the effect to eliminate M. tuberculosis in vivo. CONCLUSIONS: In this study we found that loading the antimicrobial peptide NZX into MSPs increased the inhibition of intracellular mycobacteria in primary macrophages and preserved the ability to eliminate M. tuberculosis in vivo in a murine model. Our studies provide evidence for the feasibility of using MSPs for treatment of tuberculosis.


Assuntos
Antibacterianos , Peptídeos Catiônicos Antimicrobianos , Mycobacterium tuberculosis/crescimento & desenvolvimento , Nanopartículas , Dióxido de Silício , Tuberculose Pulmonar/tratamento farmacológico , Animais , Antibacterianos/química , Antibacterianos/farmacocinética , Antibacterianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/química , Peptídeos Catiônicos Antimicrobianos/farmacocinética , Peptídeos Catiônicos Antimicrobianos/farmacologia , Modelos Animais de Doenças , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Nanopartículas/química , Nanopartículas/uso terapêutico , Porosidade , Dióxido de Silício/química , Dióxido de Silício/farmacocinética , Dióxido de Silício/farmacologia , Tuberculose Pulmonar/metabolismo , Tuberculose Pulmonar/microbiologia , Tuberculose Pulmonar/patologia
13.
Drug Dev Ind Pharm ; 45(5): 703-714, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30557053

RESUMO

Emergence of multidrug resistance (MDR) has limited the success of chemotherapeutic agents. Reversal of drugs efflux systems through combination therapy has got wider attention for increasing anticancer drugs efficacy. This study aims at co-encapsulation of Paclitaxel with Naringin in mixed polymeric micelles for enhanced anticancer activity of the drug. Drug-loaded micelles were prepared using two different amphiphilic block co-polymers and were characterized for morphology, size, zeta potential, drug encapsulation, in vitro release and stability using atomic force microscope (AFM), zetasizer, UV spectrophotometer, and FT-IR. MTT assay and fluorescence microscopy were used for in vitro cytotoxicity and cellular uptake studies. Nano-size micelles with spherical morphology and negative charge encapsulated 76.52 ± 0.94% and 32.87 0.61% Paclitaxel and Naringin, respectively. The micelles were thermally stable and retained 87.05 ± 0.69% and 92.88 ± 2.17% Paclitaxel and Naringin upon one-month storage. Maximum drug release was achieved at fourth hour of the study for both the loaded drugs. Paclitaxel co-encapsulation with Naringin synergistically improved its intracellular uptake and 65% in vitro cytotoxicity against breast cancer cells was achieved at its lower dose of 15 µg/mL. Results suggest that co-encapsulation of Paclitaxel with Naringin in mixed micelles is an effective strategy for achieving its higher anticancer activity.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Portadores de Fármacos/síntese química , Flavanonas/administração & dosagem , Neoplasias/tratamento farmacológico , Paclitaxel/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Composição de Medicamentos/métodos , Desenho de Fármacos , Liberação Controlada de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Estabilidade de Medicamentos , Flavanonas/farmacocinética , Humanos , Células MCF-7 , Micelas , Paclitaxel/farmacocinética , Polímeros/síntese química
14.
Carbohydr Polym ; 194: 89-96, 2018 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-29801862

RESUMO

Nano-carriers are excellent systems for improving bioavailability of poor aqueous soluble drugs. This study focuses fabrication of lecithin-gum tragacanth muco-adhesive hybrid NPs for enhancing Amphotericin B (AmpB) oral bioavailability. AmpB loaded lecithin NPs were synthesized through solvent diffusion method. Green synthesis of stable muco-adhesive gum tragacanth (GT) gold NPs was confirmed through UV-vis spectrophotometer and FT-IR. AmpB loaded lecithin NPs hybrid with GT gold NPs were characterized for shape, size, polydispersity index (PDI), zeta potential, drug entrapment efficiency and drug-excepients interactions using atomic force microscope (AFM), zetasizer, UV-vis spectrophotometer and FT-IR respectively. In-vivo bioavailability of AmpB loaded in NPs was investigated in rabbits. AmpB loaded muco-adhesive NPs were found polydispersed with 358.3 ±â€¯1.78 nm mean size and -19.9 ±â€¯0.51 mV zeta potential. They entrapped 78.91 ±â€¯2.44% AmpB and enhanced its oral bioavailability in animals. Results reveal the hybrid NPs as efficient carriers for enhancing AmpB oral bioavailability in controlled manner.


Assuntos
Anfotericina B/farmacocinética , Antiprotozoários/farmacocinética , Lecitinas/química , Tragacanto/química , Adesivos/síntese química , Adesivos/química , Administração Oral , Anfotericina B/administração & dosagem , Anfotericina B/química , Animais , Antiprotozoários/administração & dosagem , Antiprotozoários/química , Disponibilidade Biológica , Difusão , Portadores de Fármacos/química , Tamanho da Partícula , Coelhos , Propriedades de Superfície , Tragacanto/síntese química
15.
Artif Cells Nanomed Biotechnol ; 46(sup1): 597-607, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29381085

RESUMO

Nanomedicines anticipate drug delivery to inflamed tissues in rheumatoid arthritis (RA) with greater efficacy and lesser side effects. This study investigates the anti-arthritic potentials of Hesperidin (HP) loaded in gum acacia (GA) stabilized green silver nanoparticles (AgNPs). Synthesized GA-AgNPs were characterized through UV-vis spectrophotometer, zetasizer and atomic force microscope (AFM). The HP and its loaded NPs were tested for RA in Complete Freund's adjuvant (CFA) induced arthritis model. GA-AgNPs were found in nano-range size with negative charge, spherical shape and loaded increased HP amount. HP loaded GA-AgNPs showed minimal arthritic score exhibiting mild to moderate tissue swelling, reduced degenerative changes along with mild articular changes. Histopathological analysis revealed comparatively lesser influx of inflammatory cells and diminished granulamatous inflammation in ankle joints tissues in the presence of HP loaded GA-AgNPs. RT-PCR revealed that HP loaded GA-AgNPs significantly reduced the TLRs mRNA expression. Results validate GA stabilized green AgNPs as stable nano-cargos for targeted delivery of HP for restoring the progression of RA.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Portadores de Fármacos/química , Goma Arábica/química , Hesperidina/química , Hesperidina/uso terapêutico , Nanopartículas Metálicas/química , Prata/química , Adjuvantes Imunológicos/efeitos adversos , Animais , Artrite Reumatoide/induzido quimicamente , Artrite Reumatoide/genética , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Ratos , Ratos Wistar , Receptor 2 Toll-Like/genética , Receptor 4 Toll-Like/genética
16.
J Mater Chem B ; 6(27): 4486-4501, 2018 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-32254666

RESUMO

Bergenin (BG) is a naturally occurring C-glycoside with demonstrated anti-arthritic potential. Its therapeutic efficacy is compromised due to its lower absorption and instability at neutral-basic pH. The present study reports fabrication of gum xanthan (GX) stabilized silver nanoparticles (AgNPs) with BG for anti-arthritic activity in a CFA-induced arthritis model targeting ROS, cytokines and TLR expression. NPs were characterized through UV-vis, zetasizer, FT-IR and AFM. Oral administration of BG loaded NPs (1 mg kg-1) exhibited potent anti-arthritic activity with a minimal arthritic score, mild to moderate paw tissue swelling, reduced degenerative changes along with mild articular changes and less influx of inflammatory cells in macroscopic X-ray and histological examination. Administration of BG and its NPs suppressed the levels of reactive oxygen species (ROS) significantly as compared to the arthritic control group. Moreover, increased production of O2˙- in human neutrophils, stimulated by opsonized zymosan (OZ) and phorbol-12-myristate-13-acetate (PMA) was also suppressed. BG and its loaded NPs were revealed to antagonize the oxidative stress via interference with the NADPH oxidase metabolic pathway. Their anti-oxidant activity was further assessed by their inhibitory effect against TLR (TRL-2 & -4) and cytokine (IL-1ß, IL-6 and TNF-α) production. The current investigation validates GX stabilized AgNPs as stable and promising multi-targeted therapeutic nano-cargo for BG delivery with efficient treatment of RA.

17.
Carbohydr Polym ; 174: 243-252, 2017 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-28821064

RESUMO

Gold nanoparticles (AuNPs) have attracted greater scientific interests for the construction of drugs loading cargos due to their biocompatibility, safety and facile surface modifications. This study deals with the fabrication of gum tragacanth (GT) green AuNPs as carrier for Naringin, a less water soluble therapeutic molecule. The optimized AuNPs were characterized through UV-vis spectroscopy, FT-IR and atomic force microscope (AFM). Naringin loaded nanoparticles were investigated for their bactericidal potentials using Tetrazolium Microplate assay. Morphological studies conducted via AFM revealed spherical shape for AuNPs with nano-range size and stabilized by GT multi-functional groups. The AuNPs acted as carrier for increased amount of Naringin. Upon loading in AuNPs, Naringin An increased in the bactericidal potentials of Naringin was observed after loading on AuNPs against various tested bacterial strains. This was further authenticated by the surface morphological analysis, showing enhanced membrane destabilizing effects of loaded Naringin. The results suggest that GT stabilized green AuNPs can act as effective delivery vehicles for enhancing bactericidal potentials of Naringin.

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