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1.
Food Chem ; 329: 127168, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32512395

RESUMO

A polyphenols-rich extract was obtained from polyvinylpolypyrrolidone (PVPP) winery residue, and its neuroprotective effects and ability to modulate the kinetics of type 2 diabetes-relevant enzymes were characterized. The PVPP-white wine extract is a mixture of polyphenols (840.08 ± 161.25 µg/mg, dry weight) dominated by proanthocyanidins and hydroxycinnamic acids, affording strong antioxidant activity, as detected by the protection of membrane lipids against oxidation and superoxide radical anion scavenging activity. Regarding type 2 diabetes framework, the extract inhibits α-glucosidase (Ki = 166.9 µg/mL) and aldose reductase (Ki = 127.5 µg/mL) through non-competitive mechanisms. Despite the modest ability to inhibit rat brain acetylcholinesterase, it protects neuronal SH-SY5Y cells against oxidative damage promoted by glutamate, decreasing reactive oxygen species generation and preserving cell redox state. Thus, PVPP-white wine extract has potential to support the development of functional foods and/or nutraceuticals aiming neuroprotection and glucose homeostasis regulation, with high relevance in Alzheimers disease and type 2 diabetes interlink.


Assuntos
Diabetes Mellitus Tipo 2/enzimologia , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/farmacologia , Extratos Vegetais/farmacologia , Povidona/análogos & derivados , Vinho , Acetilcolinesterase , Aldeído Redutase/metabolismo , Animais , Antioxidantes/química , Antioxidantes/farmacologia , Linhagem Celular , Proteínas Ligadas por GPI/antagonistas & inibidores , Ácido Glutâmico/toxicidade , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Humanos , Síndromes Neurotóxicas/genética , Síndromes Neurotóxicas/prevenção & controle , Oxirredução , Extratos Vegetais/química , Polifenóis/análise , Polifenóis/farmacologia , Povidona/química , Proantocianidinas/química , Proantocianidinas/farmacologia , Ratos , Vinho/análise
2.
AAPS PharmSciTech ; 21(3): 107, 2020 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-32185564

RESUMO

Amorphous solid dispersions (ASD) are one of the most important supersaturating drug delivery systems (SDDS) for poorly water-soluble drugs to improve their bioavailability. As a result of thermodynamic instability, drug molecules tend to precipitate during storage and dissolution in gastrointestinal tract. Various precipitation inhibitors (PI) have been widely used to improve the stability in the past decade. However, most studies have investigated the inhibiting capability of PI on drug precipitation, rarely considering their potential hindering effect on the drug dissolution. The present study designed an ASD of Indomethacin (IND) and Eudragit® EPO by hot melt extrusion to investigate the influence of the added PI (PVP-K30) into ASD both on dissolution and precipitation. The precipitation study by solvent shift method indicated PVP-K30 could inhibit the precipitation of IND significantly. The dissolution study in different concentrations of PVP-K30 showed when the concentration increased above 50 µg/mL, PVP-K30 displayed an acceptable precipitation inhibition without drug concentration decline but an unexpected dissolution impediment with the reduction of maximum concentration platform. The dissolution tests of physical mixtures (PMs) of ASD and PVP-K30 also showed the precipitation inhibition and dissolution impediment when more than 2% PVP-K30 in PMs. This opposed effect of PVP-K30 was strengthen in ternary systems prepared by hot melt extruding the mixtures of IND, Eudragit® EPO and PVP-K30. All of these results proved the PI may be a double-edged sword for the opposed effects of precipitation inhibition and dissolution impediment, which should be carefully considered in the design and development of SDDS.


Assuntos
Sistemas de Liberação de Medicamentos , Indometacina/química , Povidona/química , Ácidos Polimetacrílicos , Solubilidade
3.
Int J Nanomedicine ; 15: 705-715, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32099359

RESUMO

Background: Bezafibrate is a BCS class II drug as it presents very low solubility in water; therefore, its bioavailability after oral administration is very poor. The aim of this work was to enhance solubility and dissolution rate of bezafibrate in water in order to enhance its oral bioavailability. Methods: Several formulations were prepared using PVP K30 and Cremophor ELP employing the solvent-evaporation method and the electrospraying technique. Solubility, release rate, bioavailability in male Sprague Dawley rats, and lipid profile attributes in Wistar rats were assessed in comparison with bezafibrate plain powder. Solid-state characterization was carried out using X-ray diffraction (XRD) analysis, differential scanning calorimetry (DSC), Fourier transform infrared (FTIR) spectroscopy and scanning electron microscopy (SEM). Results: All the formulations exerted positive effect towards the desired goal. In particular, the optimized formulation furnished about 14-fold enhanced solubility and 85.48 ± 10.16% drug was released in 10 min as compared with bezafibrate alone (4.06 ± 2.59%). The drug existed in the amorphous state in the prepared sample as confirmed by XRD and DSC, whilst no drug-excipient interactions were observed through FTIR analysis. Moreover, SEM revealed smooth-surfaced spherical particles of the optimized formulation. A 5.5-fold higher oral bioavailability was achieved with the optimized formulation in comparison with bezafibrate plain powder. Also, TG, LDL and TC were decreased, and HDL was increased considerably in HFD-treated rats. Conclusion: The optimized formulation consisting of bezafibrate, PVP K30 and cremophor ELP (1/12/1.5, w/w/w) might be a capable drug delivery system for orally administering poorly water-soluble bezafibrate with improved bioavailability and antihyperlipidemic effects.


Assuntos
Bezafibrato/farmacologia , Sistemas de Liberação de Medicamentos/métodos , Hipolipemiantes/farmacologia , Nanosferas/química , Polímeros/química , Administração Oral , Animais , Bezafibrato/administração & dosagem , Bezafibrato/sangue , Bezafibrato/farmacocinética , Disponibilidade Biológica , Varredura Diferencial de Calorimetria , Interações Hidrofóbicas e Hidrofílicas , Hipolipemiantes/administração & dosagem , Hipolipemiantes/sangue , Hipolipemiantes/farmacocinética , Lipídeos/química , Masculino , Nanosferas/ultraestrutura , Polietilenoglicóis/química , Povidona/química , Pós , Ratos Sprague-Dawley , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios X
4.
Aquat Toxicol ; 221: 105445, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32078886

RESUMO

Despite the widespread use of nanoparticles (NPs), there are still major gaps of knowledge regarding the impact of nanomaterials in the environment and aquatic animals. The present work aimed to study the effects of 7 and 40 nm gold nanoparticles (AuNPs) - citrate and polyvinylpyrrolidone (PVP) coated - on the liver proteome of the estuarine/marine fish gilthead seabream (Sparus aurata). After 96 h, exposure to AuNP elicited alterations on the abundance of 26 proteins, when compared to the control group. AuNPs differentially affected several metabolic pathways in S. aurata liver cells. Among the affected proteins were those related to cytoskeleton and cell structure, gluconeogenesis, amino acids metabolism and several processes related to protein activity (protein synthesis, catabolism, folding and transport). The increased abundance of proteins associated with energy metabolism (ATP synthase subunit beta), stress response (94 kDa glucose-regulated protein) and cytoskeleton structure (actins and tubulins) may represent the first signs of cellular oxidative stress induced by AuNPs. Although higher gold accumulation was found in the liver of S. aurata exposed to 7 nm PVP-AuNPs, the 7 nm cAuNPs were more bioactive, inducing more effects in liver proteome. Gold accumulated more in the spleen than in the other assessed tissues of S. aurata exposed to AuNPs, highlighting its potential role on the elimination of these NPs.


Assuntos
Ouro/toxicidade , Fígado/efeitos dos fármacos , Nanopartículas Metálicas/toxicidade , Proteoma/metabolismo , Dourada/metabolismo , Poluentes Químicos da Água/toxicidade , Animais , Ácido Cítrico/química , Fígado/metabolismo , Redes e Vias Metabólicas/efeitos dos fármacos , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Povidona/química , Proteômica , Propriedades de Superfície
5.
Colloids Surf B Biointerfaces ; 188: 110766, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31923774

RESUMO

Antibacterial dressings are an increasingly important tool for the prevention and management of wound infections, particularly in light of concerns surrounding conventional drug-resistant antibiotics. Handheld electrospinning devices provide opportunities for the rapid application of antibacterial dressing materials to wounds, but spinning formulations need to be compatible with live biological surfaces. We report the development of a new antibacterial formulation compatible with handheld electrospinning, and its manufacture directly on a wound site. Nanofibrous dressing mats were produced from polyvinyl pyrrolidone (PVP) containing isatis root (Indigowoad root or Ban-Lan-Gen), a traditional Chinese medicine, commonly used for the treatment of infectious disease. The resulting wound dressing mats of PVP/isatis root exhibited well-defined fibrous structures and excellent surface wetting, and permeability characteristics. The presence of isatis root conferred antibacterial activity against gram negative and gram positive strains. Moreover, in a Kunming mouse skin injury model, direct electrospinning of PVP/isatis root formulations on to wound sites produced near complete wound closure after 11 days and epidermal repair in histological studies.


Assuntos
Antibacterianos/farmacologia , Escherichia coli/efeitos dos fármacos , Isatis/química , Povidona/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Cicatrização/efeitos dos fármacos , Antibacterianos/química , Testes de Sensibilidade Microbiana , Tamanho da Partícula , Raízes de Plantas/química , Povidona/química , Propriedades de Superfície
6.
Pharm Res ; 37(2): 28, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31912250

RESUMO

PURPOSE: This study aims to conduct an impact investigation in the hydrophobic-hydrophilic balance as an important factor for dissolution improvement of a hydrophilic carrier-based solid dispersion system. METHODS: Polymeric carriers with different hydrophobic to hydrophilic ratios were used to prepare several electrospun solid dispersion formulations. Physicochemical properties and surface morphology of the samples were assessed using Attenuated Total Reflectance Fourier Transform Infrared (ATR-FTIR), polarized light microscopy, Differential Scanning Calorimetry (DSC), X-ray Powder Diffraction (XRPD) and Scanning Electron Microscopy (SEM). Dissolution study was conducted in a non-sink condition to assess the drug release. RESULTS: Incorporation of a higher amount of hydrophilic component showed an improvement in formulating a fully amorphous system based on XRPD, yet the dissolution rate increment showed no significant difference from the lower. Hence, the degree of crystallinity is proven not to be the crucial factor contributing to dissolution rate improvement. The presence of a concomitant hydrophobic component, however, showed ability in resisting precipitation and sustaining supersaturation. CONCLUSION: Hydrophobicity in a binary carrier system plays an important role in achieving and maintaining the supersaturated state particularly for an amorphous solid dispersion. Graphical Abstract.


Assuntos
Antimaláricos/química , Atovaquona/química , Portadores de Fármacos/química , Polivinil/química , Povidona/química , Cristalização , Composição de Medicamentos , Liberação Controlada de Fármacos , Concentração de Íons de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Cinética , Solubilidade , Solventes/química
7.
Pharm Res ; 37(2): 30, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31915939

RESUMO

PURPOSE: mRNA has recently emerged as a potent therapeutics and requires safe and effective delivery carriers, particularly prone to address its issues of poor stability and escape from endosomes. In this context, we designed poly(D,L-lactide) (PLA)-based micelles with N-succinimidyl (NS) ester decorated hydrophilic hairy corona to trap/couple a cationic fusogenic peptide and further complex mRNA. METHODS: Two strategies were investigated, namely (i) sequential immobilization of peptide and mRNA onto the micelles (layer-by-layer, LbL) or (ii) direct immobilization of peptide-mRNA pre-complex (PC) on the micelles. After characterization by means of size, surface charge, peptide/mRNA coupling/complexation and mRNA serum stability, carrier cytotoxicity and transfection capacity were evaluated with dendritic cells (DCs) using both GFP and luciferase mRNAs. RESULTS: Whatever the approach used, the micellar assemblies afforded full protection of mRNA in serum while the peptide-mRNA complex yielded complete mRNA degradation. In addition, the micellar assemblies allowed to significantly reduce the toxicity observed with the peptide-mRNA complex. They successfully transfected hard-to transfect DCs, with a superior efficiency for the LbL made ones (whatever mRNAs studied) showing the impact of the elaboration process on the carrier properties. CONCLUSIONS: These results show the relevance and potential of this new PLA/peptide based micelle platform to improve mRNA stability and delivery, while offering the possibility of further multifunctionality through PLA core encapsulation.


Assuntos
Portadores de Fármacos/química , Peptídeos/química , Poliésteres/química , Povidona/análogos & derivados , RNA Mensageiro/química , Animais , Linhagem Celular , Sobrevivência Celular , Estabilidade de Medicamentos , Expressão Gênica , Interações Hidrofóbicas e Hidrofílicas , Camundongos , Micelas , Povidona/química , RNA Mensageiro/genética , Transfecção
8.
Environ Pollut ; 257: 113551, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31801672

RESUMO

Silver nanoparticles (AgNPs) are widely used in consumer products due to their antibacterial property; however, their potential toxicity and release into the environment raises concern. Based on the limited understanding of AgNPs aggregation behavior, this study aimed to investigate the toxicity of uncoated (uc-AgNP) and coated with polyvinylpyrrolidone (PVP-AgNP), at low concentrations (0.5-100 ng/mL), under dark and visible-light exposure, using a plant test system. We exposed Allium cepa seeds to both types of AgNPs for 4-5 days to evaluate several toxicity endpoints. AgNPs did not cause acute toxicity (i.e., inhibition of seed germination and root development), but caused genotoxicity and biochemical alterations in oxidative stress parameters (lipid peroxidation) and activities of antioxidant enzymes (superoxide dismutase and catalase) in light and dark conditions. However, the light exposure decreased the rate of chromosomal aberration and micronuclei up to 5.60x in uc-AgNP and 2.01x in PVP-AgNP, and 2.69x in uc-AgNP and 3.70x in PVP-AgNP, respectively. Thus, light exposure reduced the overall genotoxicity of these AgNPs. In addition, mitotic index alterations and morphoanatomical changes in meristematic cells were observed only in the dark condition at the highest concentrations, demonstrating that light also reduces AgNPs cytotoxicity. The light-dependent aggregation of AgNPs may have reduced toxicity by reducing the uptake of these NPs by the cells. Our findings demonstrate that AgNPs can be genotoxic, cytotoxic and induce morphoanatomical and biochemical changes in A. cepa roots even at low concentrations, and that visible-light alters their aggregation state, and decreases their toxicity. We suggest that visible light can be an alternative treatment to remediate AgNP residues, minimizing their toxicity and environmental risks.


Assuntos
Nanopartículas Metálicas/toxicidade , Cebolas/efeitos dos fármacos , Prata/toxicidade , Antibacterianos/farmacologia , Antioxidantes/metabolismo , Catalase , Dano ao DNA , Luz , Peroxidação de Lipídeos , Meristema , Nanopartículas Metálicas/química , Estresse Oxidativo/efeitos dos fármacos , Raízes de Plantas , Povidona/química , Testes de Toxicidade/métodos
9.
Food Chem Toxicol ; 136: 110935, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31693913

RESUMO

Silver nanoparticles (AgNPs) represent one of the most abundant biocidal nanomaterials contained in more than 30% of nano-enabled consumer products and 75% of nanomedical products. The cumulative exposure of the general population may therefore reach critical and potentially hazardous levels. Due to data gaps on AgNP effects in humans, it is urgent to further evaluate their possible toxicity, particularly in vulnerable systems like the nervous one. As AgNPs may cross the blood brain and placental barriers, this study evaluated the in vitro effect of different AgNPs on neuronal precursor cells. For this purpose, 10 nm-sized AgNPs were stabilized with five different coating agents rendering a neutral, positive and negative surface charge. Murine neural stem cells (mNSCs) were used as cellular model to test AgNP neurotoxicity by evaluating the range of toxicity endpoints including cellular viability, apoptosis induction, oxidative stress response, cellular and mitochondrial membrane damages, DNA damage, inflammation response, and neural stem cell regulation. Our results clearly showed that the neurotoxic potential of AgNPs was not dependent on their surface charge or coating agents used for their surface stabilization. All AgNP types exhibited significant toxicity in neuronal precursor cells at an in vitro dose of 5 mg Ag/L or lower.


Assuntos
Nanopartículas Metálicas/toxicidade , Células-Tronco Neurais/efeitos dos fármacos , Prata/toxicidade , Animais , Apoptose/efeitos dos fármacos , Bovinos , Sobrevivência Celular/efeitos dos fármacos , Cetrimônio/química , Cetrimônio/toxicidade , Dano ao DNA/efeitos dos fármacos , Ácido Dioctil Sulfossuccínico/química , Ácido Dioctil Sulfossuccínico/toxicidade , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Estresse Oxidativo/efeitos dos fármacos , Polilisina/química , Polilisina/toxicidade , Povidona/química , Povidona/toxicidade , Soroalbumina Bovina/química , Soroalbumina Bovina/toxicidade , Prata/química , Transcriptoma/efeitos dos fármacos
10.
Chem Biol Interact ; 315: 108868, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31669321

RESUMO

The extensive use of silver nanoparticles (AgNPs) in manufactured products will inevitably increase environmental exposure, highlighting the importance of accurate toxicity assessments. A frequent strategy to estimate AgNP cytotoxicity is to use absorbance or fluorescent-based assays. In this study we report that AgNPs - with or without surface functionalizations (polyvinyl pyrrolidone or gum arabic), and of different sizes (2-15 nm) - can interfere with the spectrometric quantification of different dyes commonly used in cytotoxicity assays, such as 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), neutral red (NR), Hoechst, and Resazurin. Some AgNP types caused more interference than others, which was dependent on the assay. Overall most AgNPs caused the direct reduction of MTT, as well as Hoechst and NR fluorescence quenching, and absorbed light at the same wavelength as NR. None of the AgNPs tested caused the direct reduction of Resazurin; however, depending on AgNP characteristics and concentration, they may still promote fluorescence quenching of this dye. Our results show that AgNPs with different size and coatings can interfere with spectroscopy-based assays to different degrees, suggesting that their cytotoxicity may be underestimated or overestimated. We suggest that when using any spectroscopy-based assay it is essential that each individual nanoparticle formulation be tested first for potential interferences at all intended concentrations.


Assuntos
Nanopartículas Metálicas/administração & dosagem , Nanopartículas Metálicas/química , Vermelho Neutro/química , Oxazinas/química , Prata/química , Prata/farmacologia , Sais de Tetrazólio/química , Tiazóis/química , Xantenos/química , Animais , Bioensaio/métodos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Corantes , Camundongos , Tamanho da Partícula , Povidona/química , Propriedades de Superfície/efeitos dos fármacos
11.
Mater Sci Eng C Mater Biol Appl ; 106: 110130, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31753364

RESUMO

Chronic infection is a major cause of delayed wound-healing. It is recognized to be associated with infectious bacterial communities called biofilms. Currently used conventional antibiotics alone often reveal themselves ineffective, since they do not specifically target the wound biofilm. Here, we report a new conceptual tool aimed at overcoming this drawback: an antibiofilm drug delivery system targeting the bacterial biofilm as a whole, by inhibiting its formation and/or disrupting it once it is formed. The system consists of a micro/nanostructured poly(butylene-succinate-co-adipate) (PBSA)-based asymmetric membrane (AM) with controlled porosity. By the incorporation of hydrophilic porogen agents, polyvinylpyrrolidone (PVP) and polyethylene glycol (PEG), we were able to obtain AMs with high levels of porosity, exhibiting interconnections between pores. The PBSA-PEG membrane presented a dense upper layer with pores small enough to block bacteria penetration. Upon using such porogen agents, under dry and wet conditions, membrane's integrity and mechanical properties were maintained. Using bovine serum albumin (BSA) as a model protein, we demonstrated that protein loading and release from PBSA membranes were affected by the membrane structure (porosity) and the presence of residual porogen. Furthermore, the release curve profile consisted of a fast initial slope followed by a second slow phase approaching a plateau within 24 h. This can be highly beneficial for the promotion of wound healing. Cross-sectional confocal laser scanning microscopy (CLSM) images revealed a heterogeneous distribution of fluorescein isothiocyanate (FITC) labeled BSA throughout the entire membrane. PBSA membranes were loaded with dispersin B (DB), a specific antibiofilm matrix enzyme. Studies using a Staphylococcus epidermidis model, indicate significant efficiency in both inhibiting or dispersing preformed biofilm (up to 80 % eradication). The asymmetric PBSA membrane prepared with the PVP porogen (PBSA-PVP) displayed highest antibiofilm activity. Moreover, in vitro cytotoxicity assays using HaCaT and reconstructed human epidermis (RHE) models revealed that unloaded and DB-loaded PBSA-PVP membranes had excellent biocompatibility suitable for wound dressing applications.


Assuntos
Membranas Artificiais , Soroalbumina Bovina/química , Cicatrização , Adipatos/química , Animais , Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Bandagens , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Biofilmes/efeitos dos fármacos , Bovinos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Glicosídeo Hidrolases/química , Glicosídeo Hidrolases/metabolismo , Humanos , Nanoestruturas/química , Polietilenoglicóis/química , Porosidade , Povidona/química , Staphylococcus epidermidis/fisiologia , Succinatos/química , Cicatrização/efeitos dos fármacos
12.
Chemosphere ; 239: 124807, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31520982

RESUMO

The characteristics of polyvinylpyrrolidone (PVP)-stabilised nano-zero-valent iron (PVP-NZVI) and its application, combined with surfactant, to trichloroethylene (TCE)-contaminated soil were investigated. Two surfactants (cetyltrimethylammonium bromide [CTAB] and sodium dodecyl sulphate [SDS]) were tested for their ability to enhance the remedial activity of PVP-NZVI in 3 h batch experiments. The prepared PVP-NZVI formed nanoparticles ∼70 nm in diameter. The isoelectric point of PVP-NZVI was about 8.51, similar to the initial pH. X-ray diffraction and X-ray photoelectron spectroscopy analyses revealed that ZVI was the main active component of PVP-NZVI, and carbonised products of the target were observed. The TCE dechlorination efficiency by PVP-NZVI was about 84.73%; the efficiency by PVP-NZVI was about 20% higher when combined with SDS than with CTAB. Therefore, application of PVP-NZVI with SDS represents a potential remediation approach for TCE-contaminated soil.


Assuntos
Recuperação e Remediação Ambiental/métodos , Ferro/química , Solo/química , Tensoativos/química , Tricloroetileno/química , Halogenação , Nanopartículas/química , Espectroscopia Fotoeletrônica , Povidona/química , Dodecilsulfato de Sódio , Poluentes do Solo/química , Poluentes do Solo/isolamento & purificação , Difração de Raios X
13.
Eur J Pharm Biopharm ; 146: 101-110, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31841689

RESUMO

Previous studies have shown that curcumin (Cur) induced by ultrasound has protective effects on atherosclerosis even if low bioavailability of the Cur. The enhancement of bioavailability of the Cur further improved the curative effect of sonodynamic therapy (SDT) on atherosclerosis through nanotechnology. Nanosuspensions as a good drug delivery system had obvious advantages in increasing the solubility and improving the effectiveness of insoluble drugs. The aim of this study was to develop curcumin nanosuspensions (Cur-ns) which used polyvinylpyrrolidone (PVPK30) and sodium dodecyl sulfate (SDS) as stabilizers to improve poor water solubility and bioavailability of the Cur. And then the therapeutic effects of Cur-ns-SDT on atherosclerotic plaques and its possible mechanisms would be investigated and elucidated. Cur-ns with a small particle size has been successfully prepared and the data have confirmed that Cur-ns could be more easily engulfed into RAW264.7 cells than free Cur and accumulated more under the stimulation of the ultrasound. Reactive oxygen species (ROS) inside RAW264.7 cells after SDT led to the decrease of mitochondrial membrane potential (MMP) and the higher expression of cleaved caspase-9/3. The results of in vivo experiments showed that Cur-ns-SDT reduced the level of total cholesterol (TC) and low density lipoprotein (LDL) and promoted the transformation from M1 to M2 macrophages, relieved atherosclerosis syndrome. Therefore, Cur-ns-SDT was a potential treatment of anti-atherosclerosis by enhancing macrophages apoptosis through mitochondrial pathway and inhibiting the progression of plaques by interfering with macrophages polarization.


Assuntos
Aterosclerose/terapia , Curcumina/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Nanomedicina Teranóstica/métodos , Terapia por Ultrassom/métodos , Administração Oral , Animais , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Aterosclerose/sangue , Disponibilidade Biológica , Colesterol/sangue , Terapia Combinada/métodos , Curcumina/farmacocinética , Modelos Animais de Doenças , Humanos , Lipoproteínas LDL/sangue , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Potencial da Membrana Mitocondrial/efeitos da radiação , Camundongos , Camundongos Knockout para ApoE , Nanopartículas/química , Tamanho da Partícula , Veículos Farmacêuticos/química , Povidona/química , Células RAW 264.7 , Espécies Reativas de Oxigênio/metabolismo , Espécies Reativas de Oxigênio/efeitos da radiação , Dodecilsulfato de Sódio/química
14.
Int J Nanomedicine ; 14: 8285-8302, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31802866

RESUMO

Background: Curcumin has been widely used owing to its various medicinal properties including antitumor effects. However, its clinical application is limited by its instability, poor solubility and low bioavailability. Folic acid (FA)-functionalized nanoformulations may enhance the sustained release of an anticancer drug (curcumin) by tumor-specific targeting to improve therapeutic benefit. This study aims to design a nanoconjugate (NC) comprised of folate-curcumin-loaded gold-polyvinylpyrrolidone nanoparticles (FA-CurAu-PVP NPs) for targeted delivery in breast cancer model systems. Methods: We developed curcumin-loaded FA-functionalized Au-PVP NCs by layer-by-layer assembly. The folic acid-curcumin Au-PVP NCs (FA-CurAu-PVP NCs) were characterized by ultraviolet-visible spectra, Fourier transform infrared spectroscopy, X-ray powder diffraction and thermogravimetric analysis. In vitro anticancer and antimigratory effects of NCs were examined by performing MTT and wound migration assays. The in vivo antitumor efficacy of NCs was investigated using a preclinical breast cancer orthotopic mouse model. Results: Curcumin (40 µg/mL) was loaded along with conjugation of folate onto Au-PVP NPs to form FA-CurAu-PVP NCs. The size and charge of the NCs were increased gradually through layer-by-layer assembly and showed 80% release of curcumin at acidic pH. The NC did not show aggregation when incubated with human serum and mimicked an intrinsic peroxidase-like property in the presence of 3,3',5,5'-tetramethylbenzidine substrate. The MTT data using these NCs showed efficient anticancer activity at lower doses in estrogen/progesterone receptor (ER/PR)-negative cells compared with ER/PR-positive cells. Furthermore, the NCs did not show cytotoxicity at the investigated concentration in human breast epithelial and mouse fibroblast cell lines. They showed inhibitory effects on cell migration and high antitumor efficacy in in vivo analysis. Conclusion: These results suggest that folate-based tumor targeting using CurAu-PVP NCs is a promising approach for tumor-specific therapy of breast cancer without harming normal cells.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Ácido Fólico/química , Ouro/química , Nanopartículas Metálicas/química , Polímeros/química , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Curcumina/farmacologia , Curcumina/uso terapêutico , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Feminino , Humanos , Concentração de Íons de Hidrogênio , Nanopartículas Metálicas/ultraestrutura , Camundongos , Nanoconjugados/química , Povidona/química , Soro/metabolismo
15.
Pharm Res ; 37(1): 11, 2019 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-31873825

RESUMO

PURPOSE: Loss of vaccine potency due to extreme temperature exposure during storage and transport remains a significant obstacle to the success of many vaccines, including the Bacille Calmette-Guérin (BCG) vaccine, the only vaccine available against Mycobacterium tuberculosis. BCG is a live, attenuated vaccine requiring refrigerated storage for viability. In this study, we formulated a temperature-stable BCG dry powder using the spray drying technique. METHODS: We employed a factorial design to optimize our formulation of stabilizing excipients that included L-leucine, bovine serum albumin, polyvinylpyrrolidone, mannitol, and trehalose. Powders were characterized for their particle size, yield, water retention and uptake, glass transition temperature, and aerosol performance. Three optimal powder carrier mixtures were selected from the factorial design for BCG incorporation based on their stability-promoting and powder flow characteristics. Vaccine powders were also assessed for BCG viability and in vivo immunogenicity after long-term storage. RESULTS: Live BCG was successfully spray-dried using the optimized carriers. Dry powder BCG showed no loss in viability (25°C, up to 60% relative humidity; RH) and ~2-log loss in viability (40°C, 75% RH) after one year of storage. The aerodynamic size of the powders was in the respirable range. Further, when healthy mice were immunized intradermally with reconstituted BCG powders (storage for 2 years), the vaccine retained its immunogenicity. CONCLUSION: We developed a spray-dried BCG vaccine that was viable and antigenic after long-term storage. To our knowledge, this is a first study to show room temperature stability of live BCG vaccine without any loss in viability for 12 months.


Assuntos
Vacina BCG/química , Vacina BCG/farmacologia , Composição de Medicamentos/métodos , Excipientes/química , Pós/química , Aerossóis/química , Animais , Linhagem Celular , Sobrevivência Celular , Dessecação/métodos , Estabilidade de Medicamentos , Armazenamento de Medicamentos , Feminino , Humanos , Leucina/química , Manitol/química , Camundongos Endogâmicos C57BL , Mycobacterium bovis/citologia , Povidona/química , Soroalbumina Bovina/química , Temperatura , Distribuição Tecidual , Trealose/química
16.
AAPS PharmSciTech ; 21(1): 25, 2019 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-31848807

RESUMO

Alpha-arbutin is one of the most efficient skin lightener agents, which shows the effect on reducing the pigmentation by competitively inhibiting human tyrosinase. However, alpha-arbutin has difficulty in skin permeability due to its hydrophilic property. The objective of this study was, therefore, to develop alpha-arbutin-loaded dissolving microneedles (DMNs) for improving the delivery of alpha-arbutin into the skin. The DMN patch was prepared using Gantrez™ S-97, hydroxypropyl methylcellulose (HPMC), polyvinylpyrrolidone K-90 (PVP), chitosan, and their combinations. The optimal 8% alpha-arbutin-loaded DMNs, aside from Gantrez™ S-97, was successfully formulated with combination of 8% w/w HPMC and 40% w/w PVP K-90 (HPMC/PVP) at the weight ratio of 1:1. Both DMNs had 100% of penetration into porcine skin. Over 12 h of skin permeation, the flux of Gantrez™ S-97 DMNs and the HPMC/PVP DMNs were 66.21 µg/cm2/h and 74.24 µg/cm2/h, respectively. The accumulation amount of alpha-arbutin in the skin from Gantrez™ S-97 DMNs and HPMC/PVP DMNs was 107.76 µg and 312.23 µg, respectively. In comparison to the gel formulations, Gantrez™ S-97 DMNs and HPMC/PVP DMNs increase the delivery of alpha-arbutin across the skin approximately 2 and 4.7 times, respectively. In vivo studies found that alpha-arbutin-loaded HPMC/PVP DMNs delivered more alpha-arbutin into the skin than commercial cream. Moreover, the skin can reseal naturally after removal of DMNs patch without any signs of infection and remain stable in accelerated conditions for 4 weeks. Accordingly, alpha-arbutin-loaded HPMC/PVP DMNs could be a promising delivery platform for promoting trans-epidermal delivery of alpha-arbutin for skin lightening.


Assuntos
Arbutina/administração & dosagem , Epiderme/metabolismo , Derivados da Hipromelose/química , Agulhas , Povidona/química , Pele/metabolismo , Administração Cutânea , Animais , Sistemas de Liberação de Medicamentos , Humanos , Interações Hidrofóbicas e Hidrofílicas , Microinjeções , Suínos
17.
BMC Res Notes ; 12(1): 773, 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31775864

RESUMO

OBJECTIVE: Silver nanoparticles (AgNPs) can be difficult or expensive to obtain or synthesize for laboratories in resource-limited facilities. The purpose of this work was to optimize a synthesis method for a fast, facile, and cost-effective synthesis of AgNPs with antimicrobial activity, which can be readily implemented in non-specialized facilities and laboratories. RESULTS: The optimized method uses a rather simple and rapid chemical reduction process that involves the addition of a polyvinylpyrrolidone solution to a warmed silver nitrate solution under constant vigorous stirring, immediately followed by the addition of sodium borohydride. The total synthesis time is less than 15 min. The obtained AgNPs exhibit an aspect ratio close to 1, with an average size of 6.18 ± 5 nm. AgNPs displayed potent antimicrobial activity, with Minimal Inhibitory Concentration values of ≤ 4 µg mL-1 for Staphylococcus aureus and ≤ 2 µg mL-1 for Candida albicans. The resulting method is robust and highly reproducible, as demonstrated by the characterization of AgNPs from different rounds of syntheses and their antimicrobial activity.


Assuntos
Antibacterianos/síntese química , Antifúngicos/síntese química , Nanopartículas Metálicas/química , Prata/química , Antibacterianos/farmacologia , Antifúngicos/farmacologia , Boroidretos/química , Candida albicans/efeitos dos fármacos , Técnicas de Química Sintética , Nanopartículas Metálicas/ultraestrutura , Testes de Sensibilidade Microbiana , Tamanho da Partícula , Povidona/química , Nitrato de Prata/química , Staphylococcus aureus/efeitos dos fármacos
18.
Int J Pharm ; 572: 118832, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31726197

RESUMO

Solubilization and stabilization of poorly soluble drugs are important issues in the pharmaceutical industry. Herein, a Coenzyme Q10 (CQ10) solid dispersion (SD) formulation was designed to enhance CQ10 solubility, dissolution (%), and stability. CQ10 SD formulations were prepared with a dual polymer system using a melting method. The physicochemical properties of the SD formulations were evaluated. Poloxamer 407 (Kolliphor® P407) was chosen as the main solubilizer based on solubility test results, and polyvinylpyrrolidone (Kollidon® 17) was selected as the co-solubilizer based on pre-dissolution test results. Moreover, Aerosil®200 was chosen as the carrier based on pre-dissolution test results. The SD7 formulation (weight ratio, CQ10 : Aerosil® 200 : P407®: K17® = 1 : 4 : 4 : 1) showed 29-/95-/26-fold enhancement if dissolution (%), compared to that of commercial products at pH 1.2 buffer, distilled water, and pH 6.8 buffer, respectively. Moreover, the SD7 formulation was more stable than the other SD formulations at room temperature following 9 months of storage. In conclusion, a CQ10 SD formulation with significantly improved dissolution (%) and stability was developed. Thus, the SD7 formulation is expected to show improved bioavailability and effectiveness in the treatment of aging-related and cardiovascular diseases.


Assuntos
Antioxidantes/administração & dosagem , Excipientes/química , Ubiquinona/análogos & derivados , Antioxidantes/química , Química Farmacêutica , Portadores de Fármacos/química , Composição de Medicamentos , Estabilidade de Medicamentos , Armazenamento de Medicamentos , Concentração de Íons de Hidrogênio , Poloxâmero/química , Povidona/química , Dióxido de Silício/química , Solubilidade , Fatores de Tempo , Ubiquinona/administração & dosagem , Ubiquinona/química
19.
Mikrochim Acta ; 186(12): 746, 2019 11 06.
Artigo em Inglês | MEDLINE | ID: mdl-31691865

RESUMO

Well-dispersed and graft-crosslinked gold nanoparticles (AuNPs) were synthesized by the reduction of tetrachloroaurate with hydrazine at room temperature. The AuNPs possess a high density of surface defects which is due to grafting of n-octanoic acid to polyvinylpyrrolidone. The physical and chemical properties of the resulting AuNPs were characterized by UV-vis, XRD, TEM/HRTEM, SAED, and XPS, respectively. The modified AuNPs were placed on a glassy carbon electrode (GCE) in an electropolymerized taurine layer to obtain a sensitive, selective, stable and rapid electrochemical dopamine sensor. The peak current, typically measured at 0.17 V (vs. SCE), increases linearly in the 1.0 to 120 µM dopamine concentration range, and the limit of detection (at S/N = 3) is 0.16 µM with a sensitivity of 2.94 µA·µM-1·cm-2. The sensor was successfully applied to the determination of dopamine in injections and spiked serum samples. The recoveries from spiked serum samples range from 97.5 to 102.4%, with RSDs ranging between 2.8 and 3.4%. Graphical abstract Schematic representation of a glassy carbon electrode modified with in-situ graft-crosslinked gold nanoparticles combined with an electropolymerized polytaurine membrane. The sensor exhibits excellent features towards dopamine determination.


Assuntos
Dopamina/sangue , Nanopartículas Metálicas/química , Polímeros/química , Caprilatos/química , Carbono/química , Dopamina/química , Técnicas Eletroquímicas/instrumentação , Técnicas Eletroquímicas/métodos , Eletrodos , Ouro/química , Humanos , Limite de Detecção , Membranas Artificiais , Oxirredução , Polimerização , Polímeros/síntese química , Povidona/química , Reprodutibilidade dos Testes , Taurina/química
20.
Environ Int ; 133(Pt B): 105202, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31678903

RESUMO

Phenolic moieties are important constituents in dissolved organic matter (DOM) in natural and engineered systems. However, their roles in membrane fouling mechanism during drinking water treatment by ultrafiltration (UF) have remained elusive. Herein, by using water insoluble polyvinylpolypyrrolidone (PVPP) resins, we sequestered the phenolic moieties from a model DOM (Suwannee River DOM, SRDOM) and characterized their molecular profiles using electrospray ionization coupled with Fourier transform ion cyclotron resonance mass spectrometry (ESI-FT-ICR-MS). Subsequently, their roles in UF membrane fouling propensity were investigated using reconstituted DOM solutions with various concentrations of phenolic moieties. The results showed that the phenolic moieties were of higher molecular weight and rich in unsaturation cyclic structures and oxygen-rich groups. Van Krevelen diagrams revealed that the sequestered sample was rich in aromatics structures and tannins-like compounds while contained less alicyclic organic acids in comparison with the original SRDOM, which was consistent with the aromaticity index (AI) analysis. UF experiments showed that the more phenolic moieties in DOM solution, the severer decline of flux was observed. The phenolic moieties played a significant role in membrane irremovable fouling due to the hydrophobic interactions and their higher molecular weight as evidenced by membrane cleaning tests. By surface characterization, the SRDOM fouled membrane was identified to have a higher water contact angle value and abundant C-O groups, likely due to the adsorption of more hydrophobic phenolic moieties. Overall, these findings highlighted links between phenolic moieties and membrane fouling development, and implied that membrane performance could be improved by pre-removal of phenolic moieties in DOM.


Assuntos
Membranas Artificiais , Fenóis/química , Povidona/análogos & derivados , Ultrafiltração/instrumentação , Poluentes Químicos da Água/química , Purificação da Água/instrumentação , Adsorção , Espectrometria de Massas , Povidona/química , Rios
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