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1.
Molecules ; 27(4)2022 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-35209214

RESUMEN

Anti-rheumatoid arthritis (RA) effects of α-tocopherol (α-T) have been shown in human patients in a double-blind trial. However, the effects of α-T and its derivatives on fibroblast-like synoviocytes (FLS) during the pathogenesis of RA remain unclear. In the present study, we compared the expression levels of genes related to RA progression in FLS treated with α-T, succinic ester of α-T (TS), and phosphate ester of α-T (TP), as determined via RT-PCR. The mRNA levels of interleukin (IL)-6, tumor necrosis factor-α (TNF-α), matrix metalloproteinase (MMP)-3, and MMP-13 were reduced by treatment with TP without cytotoxicity, while α-T and TS did not show such effects. Furthermore, intraperitoneal injection of TP ameliorated the edema of the foot and joint and improved the arthritis score in laminarin-induced RA model mice. Therefore, TP exerted anti-RA effects through by inhibiting RA-related gene expression.


Asunto(s)
Antirreumáticos/farmacología , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , alfa-Tocoferol/análogos & derivados , Animales , Artritis Reumatoide/inducido químicamente , Citocinas/biosíntesis , Glucanos/toxicidad , Humanos , Metaloproteinasa 13 de la Matriz/biosíntesis , Metaloproteinasa 3 de la Matriz/biosíntesis , Ratones , alfa-Tocoferol/farmacología
2.
Int J Biol Macromol ; 187: 690-698, 2021 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-34343579

RESUMEN

Fermentation of Lactic Acid Bacteria (LAB) is considered to be a sustainable approach for polysaccharide production. Herein, exopolysaccharide (EPS)-producing LAB strain KM01 was isolated from Thai fermented dessert, Khao Mak, which was then identified as Leuconostoc holzapfelii. High-performance anion-exchange chromatography, nuclear magnetic resonance spectroscopy and Fourier-transform infrared spectroscopy suggested that the KM01 EPS comprises α-1,6-linked glucosides. The molecular weight of KM01 EPS was around 500 kDa, but it can form large aggregates formation (MW > 2000 kDa) in an aqueous solution, judged by transmission electron microscopy and dynamic light scattering to be around 150 nm in size. Furthermore, this KM01 EPS form highly viscous hydrogels at concentrations above 5% (w/v). The formation of hydrogels and nanoparticle of KM01 EPS was found to be reversible. Finally, the suitability of KM01 EPS for biomedical applications was demonstrated by its lack of cytotoxicity and its ability to form complexes with quercetin. Unlike the common α-1,6-linked dextran, KM01 EPS can enhance the solubility of quercetin significantly.


Asunto(s)
Excipientes/química , Glucanos/química , Leuconostoc/metabolismo , Nanopartículas , Polisacáridos Bacterianos/química , Quercetina/química , Sacarosa/metabolismo , Composición de Medicamentos , Excipientes/aislamiento & purificación , Excipientes/toxicidad , Fermentación , Glucanos/aislamiento & purificación , Glucanos/toxicidad , Hidrogeles , Peso Molecular , Polisacáridos Bacterianos/aislamiento & purificación , Polisacáridos Bacterianos/toxicidad , Solubilidad , Viscosidad
3.
Int J Biol Macromol ; 164: 4487-4498, 2020 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-32946935

RESUMEN

A new amphiphilic pullulan derivative (DBAP-PO) was obtained by grafting tertiary butyl amine and octanoyl groups on the pullulan backbone as cationic and hydrophobic moieties, respectively. The structural characteristics of the modified polymer were investigated by FT-IR and 1H and 13C NMR spectroscopy. The self-association ability in aqueous solution of DBAP-PO was studied by viscosity and fluorescence methods. The intrinsic viscosity of the polymer was determined by Wolf model. The critical aggregation concentration (CAC) value of 0.028 g/dL, determined by fluorescence measurements in the presence of pyrene, was confirmed by capillary viscosimetry and dynamic laser scattering (DLS). Dialysis method was used to demonstrate the capacity of the pullulan derivative to form spherical nanoparticles (d ~ 200 nm) loaded with model drug, sodium diclofenac (DF) (74% entrapment efficiency). The DF release was sustained and pH-dependent. In vitro cytotoxicity as well as morphological studies conducted on the human skin fibroblasts showed that DBAP-PO/DF nanoparticles do not exhibit cytotoxic effects at the pharmacologically relevant concentration of DF, maintaining the typical morphology of the cells.


Asunto(s)
Portadores de Fármacos , Glucanos/química , Nanopartículas/administración & dosificación , Cationes , Células Cultivadas , Diclofenaco/administración & dosificación , Diclofenaco/farmacocinética , Evaluación Preclínica de Medicamentos , Liberación de Fármacos , Fibroblastos/efectos de los fármacos , Glucanos/administración & dosificación , Glucanos/toxicidad , Humanos , Concentración de Iones de Hidrógeno , Interacciones Hidrofóbicas e Hidrofílicas , Estructura Molecular , Nanopartículas/química , Nanopartículas/toxicidad , Resonancia Magnética Nuclear Biomolecular , Espectroscopía Infrarroja por Transformada de Fourier , Tensoactivos/administración & dosificación , Tensoactivos/química , Tensoactivos/toxicidad , Viscosidad , Agua
4.
Int J Biol Macromol ; 161: 1189-1205, 2020 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-32504712

RESUMEN

With growing interest in polymers of natural origin, innumerable polysaccharides have gained attention for their biomedical application. Pullulan, one of the FDA approved nutraceuticals, possesses multiple unique properties which make them highly advantageous for biomedical applications. This present review encompasses the sources, production, properties and applications of pullulan. It highlights various pullulan based stimuli-responsive systems (temperature, pH, ultrasound, magnetic), subcellular targeted systems (mitochondria, Golgi apparatus/endoplasmic reticulum, lysosome, endosome), lipid-vesicular systems (solid-lipid nanoparticles, liposomes), polymeric nanofibres, micelles, inorganic (SPIONs, gold and silver nanoparticles), carbon-based nanoplatforms (carbon nanotubes, fullerenes, nanodiamonds) and quantum dots. This article also gives insight into different biomedical, therapeutic and diagnostic applications of pullulan viz., imaging, tumor targeting, stem cell therapy, gene therapy, vaccine delivery, cosmetic applications, protein delivery, tissue engineering, photodynamic therapy and chaperone-like activities. The review also includes the toxicological profile of pullulan which is helpful for the development of suitable delivery systems for clinical applications.


Asunto(s)
Ingeniería Biomédica , Técnicas Biosensibles , Glucanos/química , Nanopartículas/química , Biodegradación Ambiental , Ingeniería Biomédica/métodos , Técnicas de Química Sintética , Portadores de Fármacos/química , Composición de Medicamentos , Sistemas de Liberación de Medicamentos , Conductividad Eléctrica , Endosomas , Glucanos/biosíntesis , Glucanos/toxicidad , Concentración de Iones de Hidrógeno , Liposomas , Terapia Molecular Dirigida , Nanotecnología , Oxidación-Reducción , Temperatura
5.
Carbohydr Polym ; 236: 116060, 2020 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-32172875

RESUMEN

Colloidal systems prepared from carbohydrates are subject of intense research due to their potential to enhance drug permeability through biological membranes, however their characteristics and performance are never compared directly. Here we report the results of a comparative investigation of a series of butylglyceryl-modified polysaccharides (chitosan, guar gum, and pullulan) that were formulated into nanoparticles and loaded with a range of model actives (Doxorubicin, Rhodamine B, Angiotensin II). Butylglyceryl-modified guar gum and corresponding pullulan nanocarriers were more stable at physiological pH compared to those obtained from modified chitosan, and studies of the in-vitro interactions with mouse brain endothelial cells (bEnd3) indicated an increased biological membrane permeability and lack of toxicity at application-relevant concentrations. No significant haemolytic effect was observed, and confocal microscopy and flow cytometry studies confirmed the efficient cellular uptake and cytoplasmic localisation of NPs. Most promising characteristics for brain drug delivery applications were demonstrated by butylglyceryl pullulan nanocarriers.


Asunto(s)
Quitosano/química , Portadores de Fármacos/química , Galactanos/química , Glucanos/química , Mananos/química , Nanopartículas/química , Gomas de Plantas/química , Angiotensina II/química , Animales , Encéfalo/citología , Quitosano/toxicidad , Doxorrubicina/química , Portadores de Fármacos/toxicidad , Liberación de Fármacos , Células Endoteliales/efectos de los fármacos , Galactanos/toxicidad , Glucanos/toxicidad , Hemólisis/efectos de los fármacos , Masculino , Mananos/toxicidad , Ratones , Nanopartículas/toxicidad , Gomas de Plantas/toxicidad , Ratas Wistar , Rodaminas/química
6.
Chem Res Toxicol ; 33(4): 915-932, 2020 04 20.
Artículo en Inglés | MEDLINE | ID: mdl-32138518

RESUMEN

Glucan (from Alcaligenes faecalis) is a polymer composed of ß-1,3-linked glucose residues, and it has been addressed in different medical fields, namely in nanotechnology, as a vaccine or a drug delivery system. However, due to their small size, nanomaterials may present new risks and uncertainties. Thus, this work aims to describe the production of glucan nanoparticles (NPs) with two different sizes, and to evaluate the influence of the NPs size on immunotoxicity. Results showed that, immediately after production, glucan NPs presented average sizes of 129.7 ± 2.5 and 355.4 ± 41.0 nm. Glucan NPs of 130 nm presented greater ability to decrease human peripheral blood mononuclear cells and macrophage viability and to induce reactive oxygen species production than glucan NPs of 355 nm. Both NP sizes caused hemolysis and induced a higher metabolic activity in lymphocytes, although the concentration required to observe such effect was lower for the 130 nm glucan NPs. Regarding pro-inflammatory cytokines, only the larger glucan NPs (355 nm) were able to induce the secretion of IL-6 and TNF-α, probably due to their recognition by dectin-1. This higher immunomodulatory effect of the larger NPs was also observed in its ability to stimulate the production of nitric oxide (NO) and IL-1ß. On the contrary, a small amount of Glu 130 NPs inhibited NO production. In conclusion, on the safe-by-design of glucan NPs, the size of the particles should be an important critical quality attribute to guarantee the safety and effectiveness of the nanomedicine.


Asunto(s)
Muerte Celular/efectos de los fármacos , Glucanos/toxicidad , Leucocitos Mononucleares/efectos de los fármacos , Nanopartículas/química , Nanopartículas/toxicidad , Alcaligenes/química , Supervivencia Celular/efectos de los fármacos , Glucanos/síntesis química , Glucanos/química , Humanos , Leucocitos Mononucleares/inmunología , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Tamaño de la Partícula , Especies Reactivas de Oxígeno/metabolismo
7.
Carbohydr Polym ; 233: 115854, 2020 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-32059905

RESUMEN

Prosopis juliflora is an invasive plant distributed throughout the world and presents metabolites of interest for cosmetology. The aim of this work was to develop a new polysaccharide-based ingredient from P. juliflora and analyze its application in a solid core formulation that upon contact with water instantly forms a gel to improve moisturizing and anti-aging skin properties. Purified extracts by gel chromatography were characterized by NMR and LC-DAD-MS-MS. The in vitro and in vivo safety, antioxidant activity, formulation development and clinical evaluation were performed. The extract was characterized as containing an α-glucan and phenolics. It was non-cytotoxic, non-phototoxic and no skin reactions were observed in vivo. Antioxidant activity were present through different mechanisms. Clinical evaluation reinforced the potential of P. juliflora in skin hydration and microrelief improvement. This innovative form proved to be a prototype of a new product and the first study of an α-glucan as a cosmetic ingredient.


Asunto(s)
Antioxidantes/farmacología , Geles/farmacología , Extractos Vegetales/farmacología , Prosopis/química , Crema para la Piel/farmacología , Adulto , Anciano , Animales , Antioxidantes/química , Antioxidantes/aislamiento & purificación , Antioxidantes/toxicidad , Células 3T3 BALB , Femenino , Flavonoides/química , Flavonoides/aislamiento & purificación , Flavonoides/farmacología , Flavonoides/toxicidad , Frutas/química , Geles/química , Geles/aislamiento & purificación , Geles/toxicidad , Glucanos/química , Glucanos/aislamiento & purificación , Glucanos/farmacología , Glucanos/toxicidad , Humanos , Masculino , Ratones , Persona de Mediana Edad , Fenoles/química , Fenoles/aislamiento & purificación , Fenoles/farmacología , Fenoles/toxicidad , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/toxicidad , Piel/efectos de los fármacos , Crema para la Piel/química , Adulto Joven
8.
Carbohydr Polym ; 216: 45-53, 2019 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-31047081

RESUMEN

Herein the construction of a strong gelatin hydrogel is presented by using pullulan dialdehyde (PDA) as a macromolecular crosslinker. The resultant PDA crosslinked gelatin hydrogels (G-PDA) exhibit extremely high mechanical strength, manifested in the achieved optimal compressive stress of 5.80 MPa at 80% strain, which is up to 152 times higher than pure gelatin hydrogel. The G-PDA were characterized by Fourier transform infrared (FTIR) spectroscopy and scanning electron microscopy (SEM). The extent of crosslinking was determined by ninhydrin assay. The results suggested that the synergistic effect of dual-crosslinking, which is composed of short- and long-range covalent crosslinking and thermoreversible physical crosslinking, may played a key role in enhancing the load-bearing capacity of ensuing hydrogels. The swelling and enzymatic degradation of G-PDA are gradually limited with increasing PDA concentration. The result from MTT assay demonstrated that G-PDA is non-cytotoxic against MC3T3 cells, regardless of the concentrations of PDA.


Asunto(s)
Aldehídos/química , Materiales Biocompatibles/química , Reactivos de Enlaces Cruzados/química , Gelatina/química , Glucanos/química , Hidrogeles/química , Aldehídos/síntesis química , Aldehídos/toxicidad , Animales , Materiales Biocompatibles/síntesis química , Materiales Biocompatibles/toxicidad , Línea Celular , Colagenasas/química , Fuerza Compresiva , Reactivos de Enlaces Cruzados/síntesis química , Reactivos de Enlaces Cruzados/toxicidad , Módulo de Elasticidad , Gelatina/síntesis química , Gelatina/toxicidad , Glucanos/síntesis química , Glucanos/toxicidad , Hidrogeles/síntesis química , Hidrogeles/toxicidad , Hidrólisis , Ratones , Oxidación-Reducción , Ácido Peryódico/química , Porosidad
9.
Food Res Int ; 97: 258-264, 2017 07.
Artículo en Inglés | MEDLINE | ID: mdl-28578049

RESUMEN

Increasing the solubility of poorly water-soluble bioactives is essential to enhancing their bioavailability. The objective of this study was to evaluate the impact of phytoglycogen (PG) on water solubility of lutein and its transepithelial permeation across Caco-2 cell monolayers. Solid PG-LT complexes were prepared by combining an acetone solution of LT with an aqueous solution of PG under sonication, followed by centrifugation and vacuum drying of the supernatant as well as a further purification procedure. X-ray powder diffraction and differential scanning calorimetry showed negligible crystalline structure of LT in the PG-LT complex tested. The maximal water solubility of LT (130.65µg/mL) occurred at the PG/LT combination ratio of 53.3/1, which was significantly higher than that of LT alone (0.56µg/mL). Remarkably, LT, when complexed with PG, exhibited much-enhanced permeation through Caco-2 monolayer than LT alone, suggesting a potential role of PG to improve LT bioavailability. This study indicated that PG could be applied for the delivery of LT and possibly other hydrophobic ingredients.


Asunto(s)
Glucanos/química , Luteína/química , Luteína/metabolismo , Fitoquímicos/química , Disponibilidad Biológica , Células CACO-2 , Supervivencia Celular/efectos de los fármacos , Glucanos/metabolismo , Glucanos/toxicidad , Humanos , Luteína/toxicidad , Modelos Biológicos , Fitoquímicos/metabolismo , Fitoquímicos/toxicidad , Solubilidad
10.
Carbohydr Polym ; 170: 33-42, 2017 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-28522001

RESUMEN

A mannogalactoglucan (RK2-Ab; Mw 1.8×104gmol-1) composed by Man (27.3%), Gal (24.4%) and Glc (48.3%) was extracted and characterized from Agaricus bisporus, and its biological activity was evaluated on human hepatocarcinoma cells (HepG2). The partially-O-methylated alditol acetates together with the NMR data suggest the main chain to be composed of α-d-Galp (32.8%) and ß-d-Glcp (37.0%) units (1→6)-linked, with ß-d-Manp (14.6%), as non-reducing end units, substituting the side chains at O-2 (α-d-Galp units; 3.3%) and O-2 and O-4 (ß-d-Glcp units; 3.6%). (1→2)-linked ß-d-Glcp (2.7%) and ß-d-Manp (6.0%) can also be observed. RK2-Ab reduced cellular viability of HepG2 cells, by both, the MTT and lactate dehydrogenase release assays, promoted the increase of cytochrome c release and decrease of ATP content. Suggesting that the mannogalactoglucan from A. bisporus may have antitumor activity by inducing apoptosis by the mitochondrial death pathway, and could be used in cancer therapy.


Asunto(s)
Agaricus/química , Supervivencia Celular/efectos de los fármacos , Galactanos/farmacología , Glucanos/farmacología , Polisacáridos Bacterianos/farmacología , Antineoplásicos/química , Antineoplásicos/aislamiento & purificación , Antineoplásicos/farmacología , Antineoplásicos/toxicidad , Citocromos c/metabolismo , Galactanos/química , Galactanos/aislamiento & purificación , Galactanos/toxicidad , Glucanos/química , Glucanos/aislamiento & purificación , Glucanos/toxicidad , Células Hep G2 , Humanos , Espectroscopía de Resonancia Magnética , Polisacáridos Bacterianos/química , Polisacáridos Bacterianos/aislamiento & purificación , Polisacáridos Bacterianos/toxicidad
11.
Drug Deliv ; 24(1): 20-29, 2017 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-28155331

RESUMEN

We report asialoglycoprotein receptor (ASGPR)-targeted doxorubicin hydrochloride (Dox) nanoparticles (NPs) for hepatocellular carcinoma (HCC). Polyethylene sebacate (PES)-Gantrez® AN 119 Dox NPs of average size 220 nm with PDI < 0.62 and ∼20% Dox loading were prepared by modified nanoprecipitation. ASGPR ligands, pullulan (Pul), arabinogalactan (AGn), and the combination (Pul-AGn), were anchored by adsorption. Ligand anchoring enabled high liver uptake with a remarkable hepatocyte:nonparenchymal cell ratio of 85:15. Furthermore, Pul-AGn NPs exhibited an additive effect implying incredibly high hepatocyte accumulation. Galactose-mediated competitive inhibition confirmed ASGPR-mediated uptake of ligand-anchored NPs in HepG2 cell lines. Subacute toxicity in rats confirmed the safety of the NP groups. However, histopathological evaluation suggested mild renal toxicity of AGn. Pul NPs revealed sustained reduction in tumor volume in PLC/PRF/5 liver tumor-bearing Nod/Scid mice up to 46 days. Extensive tumor necrosis, reduced collagen content, reduction in the HCC biomarker serum α-fetoprotein (p < 0.05), a mitotic index of 1.135 (day 46), and tumor treated/tumor control (T/C) values of <0.42 signified superior efficacy of Pul NPs. Furthermore, weight gain in the NP groups, and no histopathological alterations indicated that they were well tolerated by the mice. The high efficacy coupled with greater safety portrayed Pul Dox NPs as a promising nanocarrier for improved therapy of HCC.


Asunto(s)
Antibióticos Antineoplásicos/administración & dosificación , Receptor de Asialoglicoproteína/metabolismo , Carcinoma Hepatocelular/tratamiento farmacológico , Doxorrubicina/administración & dosificación , Portadores de Fármacos , Glucanos/metabolismo , Neoplasias Hepáticas/tratamiento farmacológico , Nanopartículas , Poliésteres/química , Animales , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/metabolismo , Antibióticos Antineoplásicos/toxicidad , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Colágeno/metabolismo , Doxorrubicina/química , Doxorrubicina/metabolismo , Doxorrubicina/toxicidad , Composición de Medicamentos , Femenino , Galactanos/química , Galactanos/metabolismo , Glucanos/química , Glucanos/toxicidad , Células Hep G2 , Humanos , Ligandos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Ratones Endogámicos NOD , Ratones SCID , Mitosis/efectos de los fármacos , Índice Mitótico , Nanomedicina , Necrosis , Poliésteres/toxicidad , Ratas Sprague-Dawley , Tecnología Farmacéutica/métodos , Factores de Tiempo , Distribución Tisular , Pruebas de Toxicidad Subaguda , Carga Tumoral/efectos de los fármacos , Ensayos Antitumor por Modelo de Xenoinjerto , alfa-Fetoproteínas/metabolismo
12.
Eur J Pharm Sci ; 100: 56-63, 2017 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-28063967

RESUMEN

Tioconazole-loaded nanocapsule suspensions and its coating with a cationic polymer were developed for nail drug delivery. The colloidal systems presented a nanometric size around 155nm for uncoated nanoparticles and 162nm for those with the cationic coating, with negative and positive zeta potential values, respectively. Both nanosuspensions showed drug content close to theoretical values (1mgmL-1), association efficiency close to 100% (HPLC) and were able to control tioconazol release. The developed formulations showed in vitro antifungal activity (agar diffusion method) against C. albicans. The cationic nanocapsules were considered bioadhesive, showed higher viscosity and were chosen to be incorporated into an ungueal formulation. Pullulan nanobased nail formulation showed adequate viscosity for nail application and drug content close to the theoretical values. It was equivalent to the commercial formulation Trosid® in preventing nail infection by T. rubrum in an in vitro onychomycosis model. The nanocapsule suspensions and Pullulan nanobased nail formulation showed lower irritant potential than the commercial formulation and than free drug in an in vitro evaluation. Pullulan nanobased nail formulation is promising for the treatment of onychomycosis.


Asunto(s)
Antifúngicos/administración & dosificación , Glucanos/administración & dosificación , Imidazoles/administración & dosificación , Irritantes/administración & dosificación , Nanopartículas/administración & dosificación , Adhesividad , Animales , Antifúngicos/química , Antifúngicos/uso terapéutico , Antifúngicos/toxicidad , Candida albicans/efectos de los fármacos , Pollos , Membrana Corioalantoides/efectos de los fármacos , Sistemas de Liberación de Medicamentos , Liberación de Fármacos , Femenino , Glucanos/química , Glucanos/uso terapéutico , Glucanos/toxicidad , Humanos , Imidazoles/química , Imidazoles/uso terapéutico , Imidazoles/toxicidad , Irritantes/química , Irritantes/uso terapéutico , Irritantes/toxicidad , Nanopartículas/química , Nanopartículas/uso terapéutico , Nanopartículas/toxicidad , Onicomicosis/tratamiento farmacológico , Trichophyton/efectos de los fármacos
13.
Curr Drug Deliv ; 14(7): 968-980, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-27834151

RESUMEN

BACKGROUND: Current therapy for pulmonary arterial hypertension (PAH) is unable to prevent progression of disease due to continuous infusions and multiple oral administrations. This resulted in the need of novel treatment which would target directly structural vascular changes that weaken blood flow through pulmonary circulation. OBJECTIVE: The objective of present study was to develop spray dried (SD) formulation for dry powder inhaler (DPI) with enhanced aerosol performance and lung deposition by using novel bioactive, andrographolide (AGP) and carrier, scleroglucan (SCLG) with improved antihypertensive activity. The SDAGP formulation was evaluated for physicochemical properties and in vitro/in vivo lung deposition. Further, antihypertensive activity was studied by monocrotaline (MCT) induced rat model. RESULTS: The SDAGP exhibited mean median aerodynamic diameter (MMAD) and fine particle fraction (FPF) of 3.37 ± 0.47 µm and 60.24 ± 0.98%. The in vivo absorption profile of final formulation reflected increased lung deposition of AGP at the end of 24 h with no signs of inflammation and toxicity. Moreover, SDAGP formulation confirmed enhanced antihypertensive activity. CONCLUSION: The results proved use of AGP and SCLG as a novel bioactive and carrier with enhanced lung deposition and pulmonary antihypertensive activity.


Asunto(s)
Antihipertensivos , Diterpenos , Portadores de Fármacos , Inhaladores de Polvo Seco , Glucanos , Administración por Inhalación , Animales , Antihipertensivos/administración & dosificación , Antihipertensivos/química , Antihipertensivos/farmacocinética , Antihipertensivos/toxicidad , Diterpenos/administración & dosificación , Diterpenos/química , Diterpenos/farmacocinética , Diterpenos/toxicidad , Portadores de Fármacos/administración & dosificación , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/toxicidad , Liberación de Fármacos , Glucanos/administración & dosificación , Glucanos/química , Glucanos/farmacocinética , Glucanos/toxicidad , Hipertensión Pulmonar/inducido químicamente , Hipertensión Pulmonar/tratamiento farmacológico , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Masculino , Monocrotalina , Tamaño de la Partícula , Ratas Wistar
14.
Food Chem Toxicol ; 97: 57-69, 2016 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-27580979

RESUMEN

The potential toxicity of corn starch fiber was assessed and compared to polydextrose, a commonly used bulking agent with a long history of safe use in the food supply. Groups of male and female Crl:CD(SD) rats were fed 0 (control), 1,000, 3,000, or 10,000 mg/kg-bw/day corn starch fiber in the diet for 90 days. The polydextrose reference article was offered on a comparable regimen at 10,000 mg/kg-bw/day. Following a single gavage dose of [14C]-corn starch fiber on study day 13 or 90, the mass balance of the test article was assessed by analysis of excreta samples collected from 0 to 168 h post-dose. There were no toxicologically or biologically relevant findings in any of the test article-treated groups. The few minor differences observed between the corn starch fiber and polydextrose exposed groups were considered to be due to normal biological variation. Following [14C]-corn starch fiber dosing, nearly complete excretion of the administered dose occurred over 168 h post-dosing, with the majority excreted in the feces. The dietary no-observed-adverse-effect level of corn starch fiber after 90 days was 10,000 mg/kg-bw/day. Similar toxicity profiles for corn starch fiber and polydextrose were observed due to the structural and compositional similarities of these materials.


Asunto(s)
Radioisótopos de Carbono/análisis , Fibras de la Dieta/toxicidad , Heces/química , Almidón/toxicidad , Administración Oral , Animales , Fibras de la Dieta/administración & dosificación , Relación Dosis-Respuesta a Droga , Femenino , Aditivos Alimentarios/administración & dosificación , Aditivos Alimentarios/toxicidad , Glucanos/administración & dosificación , Glucanos/toxicidad , Masculino , Nivel sin Efectos Adversos Observados , Ratas , Ratas Sprague-Dawley , Almidón/administración & dosificación
15.
Regul Toxicol Pharmacol ; 80: 71-81, 2016 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-27311684

RESUMEN

Euglena gracilis is a microalga capable of synthesizing various nutrients of interest in human and animal nutrition. When cultivated aerobically in the dark, Euglena synthesize paramylon, a storage polysaccharide comprised of high molecular weight beta-1,3-D-glucose polymers organized in cytoplasmic granules. Beta-glucans have been shown to have immune modulation effects, including anti-microbial, anti-tumor, and anti-oxidant properties, and metabolic effects, such as regulation of cholesterol and blood sugar levels. Preparations of E. gracilis and paramylon may therefore have potential utility as functional food ingredients for human and animal nutrition. A battery of toxicological studies was conducted on a dried preparation of E. gracilis and paramylon to support their safe food use. The dried alga was not genotoxic in a bacterial reverse mutation test and mammalian micronucleus test. In the subchronic toxicity study, rats were provided E. gracilis in the diet at levels of 0, 12,500, 25,000 or 50,000 ppm. Paramylon was provided at a concentration of 50,000 ppm. No effects that could be attributable to treatment were observed in clinical observations, body weight, food consumption, ophthalmology, hematology and clinical chemistry, urinalysis, and macroscopic and microscopic findings. A NOAEL of 50,000 ppm in the diet was determined for both ingredients.


Asunto(s)
Euglena gracilis/metabolismo , Inocuidad de los Alimentos , Alimentos Funcionales/toxicidad , Glucanos/toxicidad , Pruebas de Mutagenicidad/métodos , Pruebas de Toxicidad Subcrónica/métodos , Administración Oral , Animales , ADN Bacteriano/efectos de los fármacos , ADN Bacteriano/genética , Desecación , Relación Dosis-Respuesta a Droga , Femenino , Glucanos/administración & dosificación , Glucanos/metabolismo , Humanos , Masculino , Micronúcleos con Defecto Cromosómico/inducido químicamente , Pruebas de Micronúcleos , Mutagénesis , Nivel sin Efectos Adversos Observados , Polvos , Ratas Sprague-Dawley , Medición de Riesgo , Factores de Tiempo
16.
Int J Biol Macromol ; 86: 129-38, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-26800902

RESUMEN

Pullulan, a neutral polysaccharide, was chemically modified in order to obtain two charged derivatives: reaction with SO3(.)DMF complex afforded a sulfate derivative (SP), while reaction with glycidyltrimethylammonium chloride gave a quaternary ammonium salt (AP). The presence of the charged groups was confirmed by FTIR. Assessment of the positions where the reaction took place was based on (1)H- and (13)C NMR (COSY, HSQC-TOCSY, HSQC-DEPT, and HMBC) experiments. Estimation of the degree of substitution (DS) was made from elemental analysis data, and further confirmed by NMR peak areas in the case of AP. These new derivatives showed the capability to condense with each other, forming nanoparticles with the ability to associate a model protein (BSA) and displaying adequate size for drug delivery applications, therefore making them good candidates for the production of pullulan-based nanocarriers by polyelectrolyte complexation.


Asunto(s)
Portadores de Fármacos/química , Glucanos/química , Nanopartículas , Animales , Bovinos , Línea Celular , Supervivencia Celular/efectos de los fármacos , Portadores de Fármacos/síntesis química , Portadores de Fármacos/toxicidad , Estabilidad de Medicamentos , Glucanos/síntesis química , Glucanos/toxicidad , Enlace de Hidrógeno , Muramidasa/metabolismo , Polielectrolitos/química , Compuestos de Amonio Cuaternario/química , Albúmina Sérica Bovina/química , Electricidad Estática , Sulfatos/química
17.
J Toxicol Sci ; 41(1): 33-44, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26763391

RESUMEN

Resistant glucan mixture (RGM), a water-soluble dietary fiber produced by the random polymerization of glucose with activated carbon as a catalyst at a high temperature, has been recently developed by our group. There has been little physiological and safety research into RGM and therefore we now present our research into its safety. A reverse mutation assay indicated that RGM is not mutagenic either with or without metabolic activation. We conducted a 90-day subchronic oral toxicity study in rats. Male and female rats fed either a 3% or 5% w/w RGM diet had no muddy or watery stools, and there was no RGM-related death in any group. Although some parameters in the 3% and 5% w/w groups were significantly different from those in the control group, these changes were not due to any toxicity from RGM. The results indicated that the No Observed Adverse Effect Level (NOAEL) of RGM was 3.3 and 3.9 g/kg body weight (BW) per day in male and female rats, respectively. We then studied the gastrointestinal effects of RGM in healthy adult humans. Gastrointestinal symptoms, such as gurgling sounds, flatus and tenesmus, were mild and transient. In men and women, the maximum no-effect dose for diarrhea was more than 0.9 g RGM /kg BW. The results of our current safety assessment studies suggest that RGM is safe for human consumption.


Asunto(s)
Fibras de la Dieta/toxicidad , Glucanos/toxicidad , Administración Oral , Animales , Catálisis , Carbón Orgánico/química , Fibras de la Dieta/administración & dosificación , Femenino , Tracto Gastrointestinal/efectos de los fármacos , Tracto Gastrointestinal/fisiología , Glucanos/administración & dosificación , Glucosa/química , Calor , Humanos , Masculino , Nivel sin Efectos Adversos Observados , Polimerizacion , Polvos , Ratas Sprague-Dawley , Seguridad , Solubilidad , Factores de Tiempo , Agua
18.
J Nanosci Nanotechnol ; 15(9): 6405-12, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26716194

RESUMEN

It is recognized that the stability and journey in the body of nanoparticles are important issues for drug formulations. In this study, we prepared folate-conjugated pullulan acetate nanoparticles (FPANs) and epirubicin loaded FPANs (FPA/EPI) using dialysis method. The storage stability of FPANs and FPA/EPI at 4 degrees C could be up to 3 months. Using folate receptor overexpressed Hela cells, dose dependent cellular uptake and receptor-mediated endocytosis of FPA/EPI were confirmed. From the in vivo pharmacokinetics test, compared to free EPI, half-life time (t½) of FPA/EPI was extended 1.57 times and the area under-the-curve (AUC) increased 3.95 times as well. In addition, biodistribution data showed that, EPI concentration in tumor in FPA/EPI group was 2.01 times higher than that in free EPI group after 96 h; The concentration of drug in liver treated by FPA/EPI was 5.7-11.6 times, while in heart, kidney, especially in stomach and intestine were much lower than those in free EPI group from 24 to 96 h. Furthermore, blank FPANs showed no apparent acute toxicity at dose up to 125 mg/kg. All results suggested that FPA/EPI showed a promising potential on treating cervical carcinoma and its metastatic hepatocellular carcinoma in future because of the high stability, less toxicity and tumor targeting.


Asunto(s)
Antineoplásicos/farmacocinética , Portadores de Fármacos/toxicidad , Epirrubicina/farmacocinética , Ácido Fólico/farmacocinética , Glucanos/toxicidad , Nanopartículas/toxicidad , Animales , Antineoplásicos/química , Antineoplásicos/farmacología , Peso Corporal/efectos de los fármacos , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Estabilidad de Medicamentos , Epirrubicina/química , Epirrubicina/farmacología , Femenino , Ácido Fólico/química , Glucanos/química , Células HeLa , Humanos , Masculino , Ratones , Ratones Endogámicos ICR , Ratones Desnudos , Nanopartículas/química , Ratas Wistar , Distribución Tisular , Neoplasias del Cuello Uterino
19.
Sci Rep ; 5: 12945, 2015 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-26256047

RESUMEN

Cigarette smoke induces injury and neutrophilic inflammation in the airways of smokers. The stability and activity of inflammatory effectors, IL8 and neutrophil elastase (NE), can be prolonged by binding to airway heparan sulfate (HS)/syndecan-1, posing risk for developing chronic obstructive pulmonary disease(COPD). We hypothesize that antagonizing HS/syndecan-1 binding of the inflammatory effectors could reduce smoking-related neutrophil-mediated airway inflammation. Analysis of bronchoalveolar lavage fluid(BALF) of COPD patients found both total and unopposed NE levels to be significantly higher among smokers with COPD than non-COPD subjects. Similar NE burden was observed in smoke-exposed rats compared to sham air controls. We chose sulfated-maltoheptaose(SM), a heparin-mimetic, to antagonize HS/sydecan-1 binding of the inflammatory mediators in airway fluids and lung tissues of the smoke-exposed rat model. Airway treatment with SM resulted in displacement of CINC-1 and NE from complexation with bronchio-epithelial HS/syndecan-1, dissipating the chemokine gradient for neutrophil flux across to the bronchial lumen. Following SM displacement of NE from shed HS/syndecan-1 in bronchial fluids, NE became accessible to inhibition by α1-antitrypsin endogenous in test samples. The antagonistic actions of SM against syndecan-1 binding of NE and CINC-1 in smoke-exposed airways suggest new therapeutic opportunities for modulating airway inflammation in smokers with SM delivery.


Asunto(s)
Glucanos/química , Inflamación/metabolismo , Neutrófilos/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/patología , Fumar , Sindecano-1/metabolismo , Anciano , Animales , Bronquios/metabolismo , Líquido del Lavado Bronquioalveolar/química , Líquido del Lavado Bronquioalveolar/citología , Estudios de Casos y Controles , Quimiocina CXCL1/metabolismo , Quitosano/química , Modelos Animales de Enfermedad , Ensayo de Inmunoadsorción Enzimática , Femenino , Glucanos/toxicidad , Heparitina Sulfato/química , Heparitina Sulfato/metabolismo , Humanos , Mediadores de Inflamación/metabolismo , Elastasa de Leucocito/metabolismo , Masculino , Persona de Mediana Edad , Neutrófilos/efectos de los fármacos , Neutrófilos/enzimología , Peroxidasa/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Ratas , Ratas Sprague-Dawley , Sindecano-1/química , alfa 1-Antitripsina/análisis
20.
Toxicol Sci ; 147(1): 104-15, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26048652

RESUMEN

Xyloglucan-block-polycaprolactone (XGO-PCL) copolymer nanoparticles have been proposed as nanocarriers for drug delivery. However, the possible harmful effects of exposure to nanoparticles still remain a concern. Therefore, the aim of this study is to evaluate the potential toxicity of XGO-PCL nanoparticles using in vitro and in vivo assays. Cytotoxicity and genotoxicity studies were conducted on MRC-5 human fetal lung fibroblast cells upon exposure to XGO-PCL nanoparticles. No significant reduction in the cell viability and no DNA damage were observed at the different concentrations tested. Erythrocyte toxicity was assessed by the incubation of nanoparticles with human blood. XGO-PCL nanoparticles induced a hemolytic ratio of less than 1%, indicating good blood compatibility. Finally, the subacute toxicity of XGO-PCL nanoparticles (10 mg/kg/day) was evaluated in BALB/c mice when administered orally or intraperitoneally for 14 days. Results of the in vivo toxicity study showed no clinical signs of toxicity, mortality, weight loss, or hematological and biochemical alterations after treatment with nanoparticles. Also, microscopic analysis of the major organs revealed no histopathological abnormalities, corroborating the previous results. Thus, it can be concluded that XGO-PCL nanoparticles induced no effect indicative of toxicity, indicating their potential use as drug delivery systems.


Asunto(s)
Sistemas de Liberación de Medicamentos/efectos adversos , Glucanos/toxicidad , Nanopartículas/toxicidad , Poliésteres/toxicidad , Xilanos/toxicidad , Animales , Apoptosis/efectos de los fármacos , Recuento de Células Sanguíneas , Peso Corporal/efectos de los fármacos , Línea Celular , Supervivencia Celular/efectos de los fármacos , Daño del ADN , Eritrocitos/efectos de los fármacos , Femenino , Hemólisis/efectos de los fármacos , Humanos , Ratones , Ratones Endogámicos BALB C , Mutágenos/toxicidad , Polímeros
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