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1.
Food Chem ; 302: 125343, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31430630

RESUMO

Pectin was extracted from blueberry powder as water soluble fraction (WSF), rich in branched regions, and chelator soluble fraction (CSF), linear, with strong negative charge. Binding of pectins with three anthocyanin standards (malvidin-3-glucoside; M3G, cyanidin-3-glucoside; C3G, and delphinidin-3-glucoside; D3G) and blueberry extract (BBE) were used. Without blueberry pectin, M3G was the most stable followed by C3G, whereas D3G completely disappeared after gastrointestinal digestion. CSF prevented M3G and C3G degradation more than WSF, the in vitro stability was highest with CSF and C3G. Increased stability of anthocyanins after simulated gastrointestinal digestion suggests that anthocyanins can be transported to colon where gut microbiota actively produce anthocyanin metabolites. The amount of bound anthocyanins that interacted with blueberry pectin increased as the number of hydroxyl groups increased on anthocyanins. Hydrogen bonding in addition to electrostatic interaction contribute to stability of pectin-anthocyanins interaction at pH 4.0 and contribute to stability under gastrointestinal simulation.


Assuntos
Antocianinas/química , Antocianinas/farmacocinética , Mirtilos Azuis (Planta)/química , Pectinas/química , Antocianinas/metabolismo , Digestão , Glucosídeos/química , Glucosídeos/metabolismo , Glucosídeos/farmacocinética , Ligação de Hidrogênio , Concentração de Íons de Hidrogênio , Pectinas/metabolismo , Pectinas/farmacocinética , Extratos Vegetais/química , Eletricidade Estática
2.
Molecules ; 24(14)2019 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-31373330

RESUMO

Zein composite particles coated with caseinate-pectin electrostatic complexes (zein-caseinate-pectin particles) were fabricated using an electrostatic deposition and liquid-liquid dispersion method without heating treatment. Compared to zein particles coated only with caseinate, the acidic stability of zein-caseinate-pectin particles was greatly improved, and the particle aggregation was suppressed at pH 3-6, especially at pH values near the isoelectric point of caseinate (pH 4-5). Besides, desirable long-term storage stability and re-dispersibility were observed. Under different zein to curcumin (Cur) feeding ratios (10:1, 20:1, 30:1 and 40:1, w/w), the Cur-loaded zein-caseinate-pectin particles had a spherical shape with an average diameter ranging from 358.37 to 369.20 nm, a narrow size distribution (polydispersity index < 0.2) and a negative surface charge ranging from -18.87 to -19.53 mV. The relatively high encapsulation efficiencies of Cur (81.27% to 94.00%) and desirable re-dispersibility were also achieved. Fluorescence spectroscopy indicated that the encapsulated Cur interacted with carrier materials mainly through hydrophobic interactions. The in-vitro release profile showed a sustained release of Cur from zein-caseinate-pectin particles in acidic aqueous environment (pH 4) up to 24 h, without any burst effect. In addition, the encapsulation retained more ABTS•+ radical scavenging capacity of Cur during 4 weeks of storage. These results suggest that zein-caseinate-pectin particles may be used as a potential delivery system for lipophilic nutrients in acidic beverages.


Assuntos
Caseínas , Curcumina , Nanopartículas/química , Pectinas , Zeína , Cápsulas , Caseínas/farmacocinética , Curcumina/química , Curcumina/farmacocinética , Concentração de Íons de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Pectinas/química , Pectinas/farmacocinética , Eletricidade Estática , Zeína/química , Zeína/farmacocinética
3.
Artif Cells Nanomed Biotechnol ; 46(sup3): S661-S670, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30307317

RESUMO

Hepatocellular carcinoma (HCC) is one of the greatest public health problems worldwide, and chemotherapy remains the major approach for the HCC treatment. Doxorubicin (DOX) is one of the anthracycline antibiotics but its clinical use is limited due to its severe cardiotoxicity. In this study, novel hybrid nanoparticles by self-assembling based on pectin-doxorubicin conjugates (PDC-NPs) were fabricated for HCC treatment. The stabilized structure of the PDC-NPs was characterized by methylene blue absorption, the size, zeta potential and the morphology, which was investigated by Zetasizer nanoparticle analyzer and transmission electron microscope (TEM), of nanoparticles. The PDC-NPs achieved a sustained and prolonged release ability, which was illustrated with in vitro drug release profiles, anti-cell proliferation study, cellular uptake assay and in vivo pharmacokinetics analysis. Biocompatibility of the PDC-NPs was assessed with bovine serum albumin (BSA) adsorption test, hemolysis activity examination and viability evaluation of human umbilical vein endothelial cells. Importantly, in vivo studies of the PDC-NPs, which were performed in the athymic BALB/c nude mice, demonstrated that the PDC-NPs significantly reduced the lethal side effect of DOX. Additionally, the H&E staining and serum biochemistry study further confirmed the excellent biological security of the PDC-NPs.


Assuntos
Carcinoma Hepatocelular , Doxorrubicina , Neoplasias Hepáticas , Nanopartículas , Pectinas , Animais , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Preparações de Ação Retardada/farmacologia , Doxorrubicina/química , Doxorrubicina/farmacocinética , Doxorrubicina/farmacologia , Células Hep G2 , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanopartículas/química , Nanopartículas/uso terapêutico , Pectinas/química , Pectinas/farmacocinética , Pectinas/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto
4.
Biol Trace Elem Res ; 182(2): 257-264, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28689237

RESUMO

The objective of this study was to investigate the effects of different sources and levels of zinc (Zn) on growth performance, nutrient digestibility, serum biochemical parameters, and fur quality in growing-furring male mink. Animals in the control group were fed a basal diet with no Zn supplementation. Mink in the other nine treatments were fed the basal diet supplemented with Zn from either grade Zn sulfate (ZnSO4·7H2O), Zn glycinate (ZnGly), or Zn pectin oligosaccharides (ZnPOS) at concentrations of either 100, 300, or 900 mg Zn/kg dry matter. One hundred and fifty healthy 15-week-old male mink were randomly allocated to ten dietary treatments (n = 15/group) for a 60-day trial from mid-September to pelting in December. Mink in the Zn-POS groups had higher average daily gain than those in the control group (P < 0.05). Zn source slightly improved the feed/gain (P = 0.097). N retention was increased by Zn addition (P < 0.05). Mink supplemented with dietary Zn had higher (P < 0.05) pancreas Zn level than the control group. Fur length was greater (P < 0.05) in ZnGly and ZnPOS groups compared with the control. In addition, fur length and fur density increased (linear, P < 0.05) with Zn supplementation in the diet. In conclusion, our data show that dietary Zn addition improves growth performance by increasing nitrogen retention and fat digestibility in growing-furring mink and Z-POS is equally bioavailable to mink compared to ZnGly.


Assuntos
Pelo Animal/efeitos dos fármacos , Fenômenos Fisiológicos da Nutrição Animal/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Compostos de Zinco/farmacologia , Ração Animal/análise , Animais , Disponibilidade Biológica , Suplementos Nutricionais , Glicina/administração & dosagem , Glicina/análogos & derivados , Glicina/farmacocinética , Glicina/farmacologia , Masculino , Vison , Oligossacarídeos/administração & dosagem , Oligossacarídeos/farmacocinética , Oligossacarídeos/farmacologia , Pectinas/administração & dosagem , Pectinas/farmacocinética , Pectinas/farmacologia , Distribuição Aleatória , Fatores de Tempo , Compostos de Zinco/administração & dosagem , Compostos de Zinco/farmacocinética
5.
AAPS PharmSciTech ; 18(4): 1095-1103, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-27826799

RESUMO

This study investigated the use of a newly developed chitosan-Ca pectinate microbead formulation for the colon-targeted delivery of anti-A/B toxin immunoglobulin of egg yolk (IgY) to inhibit toxin binding to colon mucosa cells. The effect of the three components (pectinate, calcium chloride, and chitosan) used for the microbead production was examined with the aim of identifying the optimal levels to improve drug encapsulation efficiency, swelling ratio, and cumulative IgY release rate. The optimized IgY-loaded bead component was pectin 5% (w/v), CaCl2 3% (w/v), and chitosan 0.5% (w/v). Formulated beads were spherical with 1.2-mm diameter, and the drug loading was 45%. An in vitro release study revealed that chitosan-Ca pectinate microbeads inhibited IgY release in the upper gastrointestinal tract and significantly improved the site-specific release of IgY in the colon. An in vivo rat study demonstrated that 72.6% of biologically active IgY was released specifically in the colon. These results demonstrated that anti-A/B toxin IgY-loaded chitosan-Ca pectinate oral microbeads improved IgY release behavior in vivo, which could be used as an effective oral delivery platform for the biological treatment of Clostridium difficile infection (CDI).


Assuntos
Proteínas de Bactérias/metabolismo , Toxinas Bacterianas/metabolismo , Quitosana , Infecções por Clostridium/tratamento farmacológico , Colo , Enterotoxinas/metabolismo , Imunoglobulinas , Pectinas , Animais , Antidiarreicos/administração & dosagem , Antidiarreicos/farmacocinética , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Quitosana/química , Quitosana/farmacologia , Colo/efeitos dos fármacos , Colo/microbiologia , Sistemas de Liberação de Medicamentos , Imunoglobulinas/administração & dosagem , Imunoglobulinas/farmacologia , Microesferas , Pectinas/administração & dosagem , Pectinas/farmacocinética , Ratos
6.
Mol Nutr Food Res ; 61(1)2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27396291

RESUMO

SCOPE: This study simulates the fermentation process of barley ß-glucan and sugar beet pectin in the human colon and monitors the degradation products formed. Additionally, immune effects of the degradation products were investigated. METHODS AND RESULTS: Immunostimulatory activity of fermentation digesta was investigated using bone marrow derived dendritic cells (BMDCs) from toll-like receptor 2/4 (TLR2/4) knockout mice, which were unresponsive to microbe-associated molecular patterns. Cytokine responses were elicited to dietary fibers and not to the SCFA and microbiota. The fermentation digesta were analyzed for their SCFA profiles and glycan metabolites over time. During fermentation the amount of insoluble precipitating fibers increased and induced as well as soluble molecules of lower molecular mass greater amounts of cytokines in BMDCs than the parental fiber. Additionally, high amounts of cytokines can be attributed to soluble galactose-rich beet pectin molecules. CONCLUSIONS: The fermentation of the two fibers led to fiber-specific amounts of SCFA, glycosidic metabolites, and different immunomodulatory properties. BMDC from TLR2/4 knockout mice did not respond to the digest microbiota and SCFA, making it a useful approach to study temporal effects of fermentation on the immunomodulatory effects of fibers.


Assuntos
Citocinas/metabolismo , Fezes/microbiologia , Pectinas/metabolismo , beta-Glucanas/metabolismo , Animais , Técnicas de Cultura Celular por Lotes , Beta vulgaris/química , Células Dendríticas/metabolismo , Fibras na Dieta/metabolismo , Fibras na Dieta/farmacologia , Fermentação , Hordeum/química , Humanos , Fatores Imunológicos/farmacocinética , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pectinas/farmacocinética , Receptor 2 Toll-Like/genética , beta-Glucanas/farmacocinética
7.
PLoS One ; 11(12): e0168050, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27992455

RESUMO

Drug targeting to the colon via the oral administration route for local treatment of e.g. inflammatory bowel disease and colonic cancer has several advantages such as needle-free administration and low infection risk. A new source for delivery is plant-polysaccharide based delivery platforms such as Rhamnogalacturonan-I (RG-I). In the gastro-intestinal tract the RG-I is only degraded by the action of the colonic microflora. For assessment of potential drug delivery properties, RG-I based microcapsules (~1 µm in diameter) were prepared by an interfacial poly-addition reaction. The cross-linked capsules were loaded with a fluorescent dye (model drug). The capsules showed negligible and very little in vitro release when subjected to media simulating gastric and intestinal fluids, respectively. However, upon exposure to a cocktail of commercial RG-I cleaving enzymes, ~ 9 times higher release was observed, demonstrating that the capsules can be opened by enzymatic degradation. The combined results suggest a potential platform for targeted drug delivery in the terminal gastro-intestinal tract.


Assuntos
Cápsulas/síntese química , Pectinas/farmacocinética , Animais , Cápsulas/química , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Microbioma Gastrointestinal , Trato Gastrointestinal/microbiologia , Humanos , Tamanho da Partícula , Solanum tuberosum/química
8.
Aliment Pharmacol Ther ; 44(11-12): 1183-1198, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27778367

RESUMO

BACKGROUND: Non-alcoholic steatohepatitis (NASH) and resultant liver fibrosis is a major health problem without approved pharmacotherapy. Pre-clinical results of GR-MD-02, a galectin-3 inhibitor, suggested potential efficacy in NASH with advanced fibrosis/cirrhosis and prompted initiation of a clinical development programme in NASH with advanced fibrosis. AIM: To evaluate the safety, pharmacokinetics and exploratory pharmacodynamic markers of GR-MD-02 in subjects having NASH with bridging fibrosis. METHODS: The GT-020 study was a first-in-human, sequential dose-ranging, placebo controlled, double-blinded study with the primary objective to assess the safety, tolerability and dose limiting toxicity of GR-MD-02, in subjects with biopsy-proven NASH with advanced fibrosis (Brunt stage 3). The secondary objectives were to characterise first-dose and multiple-dose pharmacokinetic profiles and to evaluate changes in potential serum biomarkers and liver stiffness as assessed by FibroScan. RESULTS: GR-MD-02 single and three weekly repeated of 2, 4 and 8 mg/kg revealed no meaningful clinical differences in treatment emergent adverse events, vital signs, electrocardiographic findings or laboratory tests. Pharmokinetic parameters showed a dose-dependent relationship with evidence of drug accumulation following 8 mg/kg (~twofold). CONCLUSIONS: GR-MD-02 doses were in the upper range of the targeted therapeutic dose determined from pre-clinical data and were safe and well tolerated with evidence of a pharmacodynamic effect. These results provide support for a Phase 2 development programme in advanced fibrosis due to NASH.


Assuntos
Galectina 3/antagonistas & inibidores , Cirrose Hepática/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Pectinas , Adulto , Idoso , Biomarcadores/sangue , Método Duplo-Cego , Feminino , Galectina 3/sangue , Humanos , Cirrose Hepática/sangue , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/sangue , Pectinas/efeitos adversos , Pectinas/sangue , Pectinas/farmacocinética , Pectinas/farmacologia
9.
Mol Nutr Food Res ; 60(10): 2256-2266, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27174558

RESUMO

SCOPE: We aimed to investigate and compare the effects of four types of pectins on dietary fiber (DF) fermentation, microbiota composition, and short chain fatty acid (SCFA) production throughout the large intestine in rats. METHODS AND RESULTS: Male Wistar rats were given diets supplemented with or without 3% structurally different pectins for 7 weeks. Different fermentation patterns of pectins and different location of fermentation of pectin and diet arabinoxylans (AXs) in the large intestine were observed. During cecal fermentation, sugar beet pectin significantly stimulated Lactobacillus (p < 0.01) and Lachnospiraceae (p < 0.05). The stimulating effects of sugar beet pectin on these two groups of microbes are stronger than both other pectins. In the cecum, low-methyl esterified citrus pectin and complex soy pectin increased (p < 0.05) the production of total SCFAs, propionate and butyrate, whereas high-methyl esterified pectin and sugar beet pectin did not. The fermentation patterns of cereal AXs in the cecum were significantly different upon supplementation of different pectins. These differences, however, became smaller in the colon due to an enhanced fermentation of the remaining DFs. CONCLUSION: Dietary supplementation of pectin is a potential strategy to modulate the location of fermentation of DFs, and consequently microbiota composition and SCFA production for health-promoting effects.


Assuntos
Fibras na Dieta/metabolismo , Microbioma Gastrointestinal/efeitos dos fármacos , Pectinas/química , Pectinas/farmacologia , Animais , Beta vulgaris/química , Ceco/metabolismo , Ceco/microbiologia , Citrus/química , Colo/metabolismo , Colo/microbiologia , Suplementos Nutricionais , Digestão , Microbioma Gastrointestinal/genética , Masculino , Pectinas/farmacocinética , Polissacarídeos/análise , Polissacarídeos/metabolismo , Ratos Wistar , Soja/química
10.
J Opioid Manag ; 11(2): 139-46, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25901479

RESUMO

OBJECTIVE: To evaluate the effects of different dosing intervals on multiple-dose pharmacokinetics, and safety and tolerability of fentanyl pectin nasal spray (FPNS). METHODS: This was an open-label study in healthy volunteers. Five FPNS treatments (1 × 100 µg; 2 × 100 µg at 4-, 2-, and 1-hour intervals, and 8 × 100 µg consecutively) were administered to the right nostril, with a ≥ 3-day washout period. Blood samples were collected at predose and up to 1,440 minutes postdose. Plasma fentanyl concentrations were determined. Pharmacokinetic parameters-peak concentration (C(max)), time to C(max) (t(max)), and area under the concentration-time curve (AUC)-were derived using noncompartmental method. For the two-dose regimens, pharmacokinetic parameters were compared between doses using a paired t-test with p < 0.05 as statistically significant. RESULTS: Thirteen subjects were enrolled and 10 completed the study. Median tmax was 10-15 minutes across five regimens. Cmax post the second dose significantly increased for 1-hour (p < 0.0001) and 2-hour (p < 0.001) but not 4-hour intervals (p = 0.462). C(max) and AUC(0-24) following 8 × 100 µg were approximately fivefold of those following 1 × 100 µg. Dizziness (11.9 percent) and somnolence (4.9 percent) were most common adverse events (AEs). 12.9 percent of patients discontinued due to AEs. CONCLUSIONS: FPNS exhibited consistently rapid t(max). When intervals between two doses were shorter, the difference in C(max) between the first and second dose was larger. All regimens of FPNS were well tolerated. Exposure reached a plateau after eight consecutive doses, suggesting potential limited absorption through the nasal mucosa.


Assuntos
Fentanila/farmacocinética , Dor/tratamento farmacológico , Pectinas/farmacocinética , Administração Intranasal , Adolescente , Adulto , Idoso , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/farmacocinética , Estudos Cross-Over , Relação Dose-Resposta a Droga , Esquema de Medicação , Combinação de Medicamentos , Feminino , Fentanila/administração & dosagem , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Sprays Nasais , Dor/metabolismo , Pectinas/administração & dosagem , Estudos Retrospectivos , Adulto Jovem
11.
J Microencapsul ; 31(3): 220-9, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24047213

RESUMO

The present work aims at the development of a low-cost controlled release system of glipizide beads embedded in pectin to overcome the problem of frequent dosing of drug. The method of preparation has been optimised by experimental design to achieve satisfactory responses with respect to controlling variables. The controlling variables are X1, drug-polymer ratio; X2, surfactant concentration and X3, isooctane-acetone ratio. The most effective combination is X1(1:6), X2(1%), X3(50:50). Various parameters such as mucoadhesivity and swellability of beads, characterisation, dissolution, stability, ex vivo absorption and in vivo (Oral glucose tolerance test in rat) studies were performed with the optimised product. The optimised product was found quiet satisfactory that showed yield of 86.78%, drug entrapment efficiency (DEE) of 87.38% and drug release was extended up to 18 h. The present formulation of glipizide is a promising multiparticulate system of glipizide with significant hypoglycemic effect, and moreover it was prepared rapidly with ease.


Assuntos
Portadores de Fármacos , Desenho de Fármacos , Glipizida , Hipoglicemiantes , Pectinas , Adesividade , Animais , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Preparações de Ação Retardada/farmacologia , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacologia , Avaliação Pré-Clínica de Medicamentos , Glipizida/química , Glipizida/farmacocinética , Glipizida/farmacologia , Teste de Tolerância a Glucose , Hipoglicemiantes/química , Hipoglicemiantes/farmacocinética , Hipoglicemiantes/farmacologia , Pectinas/química , Pectinas/farmacocinética , Pectinas/farmacologia , Ratos , Ratos Wistar
12.
Int J Clin Pharmacol Ther ; 51(12): 942-7, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24120713

RESUMO

OBJECTIVE: Fentanyl pectin nasal spray (FPNS) is approved for management of breakthrough pain in cancer. It is available in 100 and 400 µg strength products which allow for doses of 100 - 800 µg (1 or 2 sprays). Existing titration strategies require a transition from the 100 µg product to the 400 µg product when increasing the dose from 200 to 400 µg. This study assessed the pharmacokinetic (PK) profile of FPNS administered as 4 sprays of 100 µg as an alternate titration strategy. METHODS: In this 3-way, crossover study, healthy subjects aged 18 - 65 years were randomized to receive each of 3 dosages of FPNS (4 × 100 µg, 2 × 100 µg, and 1 × 400 µg). PK samples were collected over 24 hours. RESULTS: Of 22 subjects randomized, 20 were included in the PK analysis. Administration of both 400 µg regimens (4 × 100 µg and 1 × 400 µg) provided greater systemic fentanyl exposure compared with the 200 µg dose (C(max): 1,748 and 1,485 pg/ml vs. 1,051 pg/ml; AUC(0-1h): 1,012 and 944 pg×h/ml vs. 665 pg×h/ml; and tmax: 0.25 hours and 0.50 hours vs. 0.25 hours); fentanyl exposure after 4 × 100 µg and 1 × 400 µg regimens was similar. Adverse events (AEs) were all mild or moderate in intensity; most common AEs were nausea (50%) and headache (23%). AE frequency was similar across treatments without reports of nasal effects. CONCLUSIONS: Given that systemic fentanyl exposure from FPNS administered as 4 × 100 µg is similar to that from FPNS as 1 × 400 µg, the 4 × 100 µg regimen provides an alternate titration strategy for patients needing more than 200 µg. This alternate strategy will facilitate a patient's ability to achieve an optimized FPNS regimen and reduce opioid wastage.


Assuntos
Analgésicos Opioides/farmacocinética , Fentanila/farmacocinética , Pectinas/farmacocinética , Administração Intranasal , Adulto , Estudos Cross-Over , Feminino , Fentanila/administração & dosagem , Fentanila/efeitos adversos , Humanos , Masculino , Pectinas/administração & dosagem , Pectinas/efeitos adversos
13.
Int J Nanomedicine ; 8: 2399-407, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23861585

RESUMO

Hyaluronan-cisplatin conjugate nanoparticles (HCNPs) were chosen as colon-targeting drug-delivery carriers due to the observation that a variety of malignant tumors overexpress hyaluronan receptors. HCNPs were prepared by mixing cisplatin with a hyaluronan solution, followed by dialysis to remove trace elements. The cells treated with HCNPs showed significantly lower viability than those treated with cisplatin alone. HCNPs were entrapped in Eudragit S100-coated pectinate/alginate microbeads (PAMs) by using an electrospray method and a polyelectrolyte multilayer-coating technique in aqueous solution. The release profile of HCNPs from Eudragit S100-coated HCNP-PAMs was pH-dependent. The percentage of 24-hour drug release was approximately 25.1% and 39.7% in pH 1.2 and pH 4.5 media, respectively. However, the percentage of drug released quickly rose to 75.6% at pH 7.4. Moreover, the result of an in vivo nephrotoxicity study demonstrated that Eudragit S100-coated HCNP-PAMs treatment could mitigate the nephrotoxicity that resulted from cisplatin. From these results, it can be concluded that Eudragit S100-coated HCNP-PAMs are promising carriers for colon-specific drug delivery.


Assuntos
Cisplatino/química , Ácido Hialurônico/química , Microesferas , Nanoconjugados/química , Ácidos Polimetacrílicos/química , Alginatos/química , Alginatos/farmacocinética , Animais , Peso Corporal/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cisplatino/farmacocinética , Cisplatino/farmacologia , Cisplatino/toxicidade , Neoplasias do Colo , Ácido Glucurônico/química , Ácido Glucurônico/farmacocinética , Células HCT116 , Ácidos Hexurônicos/química , Ácidos Hexurônicos/farmacocinética , Humanos , Ácido Hialurônico/farmacocinética , Ácido Hialurônico/toxicidade , Masculino , Nanoconjugados/toxicidade , Pectinas/química , Pectinas/farmacocinética , Ácidos Polimetacrílicos/farmacocinética , Ratos , Ratos Wistar
14.
J Biomater Sci Polym Ed ; 24(11): 1333-42, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23796034

RESUMO

Injectable hydrogels have advantages over pre-formed hydrogels in biomedical applications. In our previous study, we showed usefulness of sugar beet pectin (SBP) as an injectable gel material. However, the in vivo biodegradability of the gels was low because animals lack suitable hydrolytic enzymes of SBP. In this study we developed SBP-based injectable gels with higher in vivo biodegradability than the previous SBP gels by incorporating biodegradable gelatin into the latter. An aqueous solution with dissolved SBP and gelatin rapidly (< 1 min) formed gels through a horseradish peroxidase-catalyzed oxidative coupling reaction between feruloyl moieties on the SBP molecules and phenolic moieties on the gelatin molecules. Gelation time and mechanical properties of the gels were tunable by adjusting the polymer concentrations. The gels containing doxorubicin, an anti-cancer drug, successfully suppressed the growth of a solid tumor created by subcutaneous injection of mouse melanoma B16F1 cells into nude mice. These results indicate that injectable and biodegradable SBP/gelatin gels are useful in biomedical applications.


Assuntos
Beta vulgaris/química , Tecnologia Biomédica/métodos , Portadores de Fármacos/síntese química , Gelatina/administração & dosagem , Hidrogéis/administração & dosagem , Pectinas/administração & dosagem , Implantes Absorvíveis , Animais , Linhagem Celular Tumoral , Doxorrubicina/administração & dosagem , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Gelatina/química , Gelatina/farmacocinética , Hidrogéis/química , Hidrogéis/farmacocinética , Injeções , Masculino , Melanoma Experimental/tratamento farmacológico , Melanoma Experimental/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pectinas/química , Pectinas/farmacocinética , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologia
15.
Pharm Dev Technol ; 18(5): 1259-64, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-22304683

RESUMO

The aim of this study was to examine the effect of a change of the degree of esterification of pectin on the in situ gelation and release characteristics of 1.5% (w/v) pectin solutions over a wide pH range. Formulations of pectin with degrees of esterification of 9% (DE9) and 31% (DE31) containing complexed calcium ions formed gels in vitro at pH 1.2 as a consequence of cross-linking of the pectin chains by free calcium ions released from the complex. In vitro release of paracetamol from these gels was diffusion controlled. A sustained release of paracetamol was observed following oral administration of pectin DE9 and DE31 formulations to gastric acidity-controlled rats at pH 2.5 but only with DE9 formulations at pH 5.5. Examination of the stomach contents confirmed effective in situ gelation of pectin DE9 formulations at a gastric pH of 6 but there was no evidence of the gelation of pectin DE31 formulations at this pH.


Assuntos
Acetaminofen/química , Pectinas/química , Acetaminofen/administração & dosagem , Acetaminofen/farmacocinética , Administração Oral , Animais , Cálcio/metabolismo , Química Farmacêutica/métodos , Preparações de Ação Retardada/química , Difusão , Sistemas de Liberação de Medicamentos , Esterificação , Mucosa Gástrica/metabolismo , Géis/administração & dosagem , Géis/química , Concentração de Íons de Hidrogênio , Masculino , Pectinas/administração & dosagem , Pectinas/farmacocinética , Ratos , Ratos Wistar
16.
Eur J Pharm Biopharm ; 82(2): 250-61, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22885158

RESUMO

The purpose of this study was to improve in vitro dissolution and in vivo absorption of itraconazole (ITZ), a poorly water-soluble drug, by means of novel pectin-based nanoparticles prepared from nanoemulsion templates. Nanoemulsion templates were prepared by a high-pressure homogenization using pectin (i.e., 0.5-3.0%w/w low-methoxyl pectin (LMP), amidated low-methoxyl pectin (ALMP), or high-methoxyl pectin (HMP)) as an emulsifier and chloroform as an oil phase. HMP provided good oil-in-water emulsions with ITZ loaded in the oil phase. The chloroform in nanoemulsions was then removed to produce the suspensions of nanoparticles dispersed in water phase. After lyophilization, the dried core-shell nanoparticles with good properties in terms of redispersibility, dissolution, and stability were obtained. The alteration of ITZ crystallinity was clearly observed from powder X-ray diffractogram while no interaction between ITZ and pectin was found in the nanoparticles. The ITZ-loaded nanoparticles showed high percent drug dissolved, especially those prepared from HMP, and could maintain their good dissolution properties even after 6-month storage. The in vivo absorption study in fasted rats demonstrated that pectin-based nanoparticles prepared from nanoemulsion templates could improve absorption of ITZ, that is, 1.3-fold higher than the ITZ commercial product (p<0.05). Pectin type highly influenced the dissolution properties and also in vivo plasma profile. These findings suggested that HMP-based nanoparticles seem to be a promising formulation due to their high AUC(0-24h) and C(max).


Assuntos
Nanopartículas/química , Pectinas/química , Água/química , Absorção , Animais , Área Sob a Curva , Química Farmacêutica , Estabilidade de Medicamentos , Emulsões/administração & dosagem , Emulsões/química , Itraconazol/administração & dosagem , Itraconazol/química , Itraconazol/farmacocinética , Masculino , Nanopartículas/administração & dosagem , Óleos/química , Tamanho da Partícula , Pectinas/administração & dosagem , Pectinas/farmacocinética , Ratos , Ratos Wistar , Solubilidade , Suspensões/administração & dosagem , Suspensões/química
17.
An. R. Acad. Farm ; 78(1): 82-97, ene.-mar. 2012. ilus
Artigo em Espanhol | IBECS | ID: ibc-102743

RESUMO

La pectina es un polisacárido de origen vegetal que posee excelentes características de gelificación, y biocompatibilidad, por lo que ha sido ampliamente estudiada como excipiente en diversas formas farmacéuticas para modular la liberación de moléculas activas. La pectina permanece intacta en la parte alta del tracto gastrointestinal, y sólo es degradada por la microflora del colon. Por tal motivo, se ha incluido en esta revisión el desarrollo de diferentes formulaciones de liberación colónica de fármacos basadas en este polisacárido para tratar afecciones locales como el cáncer de colon y la enfermedad de Crohn. También se incluyen diversos estudios acerca de aplicaciones terapéuticas de la pectina como coadyuvante en diferentes patologías digestivas como el reflujo gastroesofágico y la diarrea persistente. El efecto que, sobre los niveles de glucosa, insulina y lípidos en plasma, puede tener una dieta rica en pectina es así mismo analizado(AU)


Pectin: Pharmaceutical and Therapeutic UsesPectin is a polysaccharide of vegetarian origin, combining both excellent gelation and biocompatibility characteristics, and thus has been widely studied as an excipient in different pharmaceutical forms in order to modulate the release of active molecules. Pectin remains intact in the upper gastrointestinal tract and only gets degraded by colonic microflora. Hence, different formulations based on this polysaccharide, which have been developed to target drugs to the colon and treat local affections like colon cancer and Crohn’s disease, were included in this review. Also, different studies on therapeutic uses of pectin as an adjuvant in various digestive pathologies such as the gastro-esophageal reflux and persistent diarrhea have been discussed. The effects of a rich pectin-diet over the glucose, insulin and lipid plasma levels are also commented(AU)


Assuntos
Animais , Masculino , Feminino , Camundongos , Pectinas/uso terapêutico , Polissacarídeo-Liase/uso terapêutico , Hidrogéis/uso terapêutico , Anticarcinógenos/uso terapêutico , Pectinas/metabolismo , Pectinas/farmacologia , Pectinas/farmacocinética , Colesterol/uso terapêutico , Teste de Materiais/métodos
18.
Support Care Cancer ; 20(3): 565-73, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21424794

RESUMO

PURPOSE: Previous studies show that fentanyl pectin nasal spray (FPNS) rapidly provides clinically meaningful pain relief in the treatment of breakthrough cancer pain (BTCP). This study assessed the long-term tolerability, acceptability and consistency of effect of FPNS in patients with BTCP. METHODS: Patients (new and rolled over from earlier controlled studies) with cancer experiencing one to four episodes per day of BTCP whilst taking ≥ 60 mg/day of morphine (or equivalent) given orally for cancer pain entered an open-label 16-week safety study. Safety and tolerability were assessed by adverse events (AEs), adverse drug reactions (ADRs), withdrawal due to AEs and by nasal assessments. Acceptability assessments included ratings of overall satisfaction with each treated episode and ease of use and convenience of FPNS. Additional rescue medication and dose stability were used to evaluate the consistency of effect. RESULTS: Four hundred three patients were included in the safety and intent-to-treat analysis (42,227 episodes), 356 entered the treatment phase and 110 completed 16 weeks. Overall, 24.6% of 403 patients reported treatment-related treatment-emergent AEs that were generally mild/moderate and typical of opioids; 20 patients discontinued treatment due to an AE (9 were ADRs). Nasal assessments revealed no clinically significant effects; 94% of FPNS-treated episodes required no additional rescue medication. More than 90% of patients did not have to increase their dose during the study. Patients reported overall satisfaction with FPNS for 90.1% of episodes. At week 12, 96.9% of patients were satisfied with the ease of use and 97.9% with the convenience of FPNS. CONCLUSIONS: FPNS was generally well tolerated and well accepted for the treatment of BTCP, and doses remained stable over the 4-month study period.


Assuntos
Dor Irruptiva/tratamento farmacológico , Fentanila/administração & dosagem , Neoplasias/complicações , Satisfação do Paciente , Absorção , Administração Intranasal , Administração Oral , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/farmacocinética , Dor Irruptiva/etiologia , Feminino , Fentanila/farmacocinética , Humanos , Masculino , Pessoa de Meia-Idade , Morfina/administração & dosagem , Mucosa Nasal/metabolismo , Sprays Nasais , Medição da Dor , Pectinas/administração & dosagem , Pectinas/farmacocinética
19.
AAPS PharmSciTech ; 12(1): 201-14, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21194013

RESUMO

Colon cancer is the fourth most common cancer globally with 639,000 deaths reported annually. Typical chemotherapy is provided by injection route to reduce tumor growth and metastasis. Recent research investigates the oral delivery profiles of chemotherapeutic agents. In comparison to injection, oral administration of drugs in the form of a colon-specific delivery system is expected to increase drug bioavailability at target site, reduce drug dose and systemic adverse effects. Pectin is suitable for use as colon-specific drug delivery vehicle as it is selectively digested by colonic microflora to release drug with minimal degradation in upper gastrointestinal tract. The present review examines the physicochemical attributes of formulation needed to retard drug release of pectin matrix prior to its arrival at colon, and evaluate the therapeutic value of pectin matrix in association with colon cancer. The review suggests that multi-particulate calcium pectinate matrix is an ideal carrier to orally deliver drugs for site-specific treatment of colon cancer as (1) crosslinking of pectin by calcium ions in a matrix negates drug release in upper gastrointestinal tract, (2) multi-particulate carrier has a slower transit and a higher contact time for drug action in colon than single-unit dosage form, and (3) both pectin and calcium have an indication to reduce the severity of colon cancer from the implication of diet and molecular biology studies. Pectin matrix demonstrates dual advantages as drug carrier and therapeutic for use in treatment of colon cancer.


Assuntos
Antineoplásicos/administração & dosagem , Antineoplásicos/farmacocinética , Neoplasias do Colo/tratamento farmacológico , Portadores de Fármacos , Pectinas , Veículos Farmacêuticos , Administração Oral , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Colo/anatomia & histologia , Sistemas de Liberação de Medicamentos , Humanos , Pectinas/química , Pectinas/farmacocinética
20.
Vopr Pitan ; 80(4): 47-55, 2011.
Artigo em Russo | MEDLINE | ID: mdl-22232883

RESUMO

Daily inclusion in the diet of Pskov GRES workers the drinks or kissels containing 2 g pectin per daily serving (cup) during 6 months was accompanied by a statistically significant decline of their supply with vitamins C, B2, A and beta-carotene. This is reflected both in reducing the average vitamin concentration in blood serum and in the increase of the quota of people with deficiency of several vitamins. Additional inclusion of 13 vitamins in these drinks and kissels, in a dose about 80% of the RDA, has prevented the deterioration of vitamin status.


Assuntos
Deficiência de Vitaminas/prevenção & controle , Bebidas , Pectinas/administração & dosagem , Vitaminas/administração & dosagem , Adulto , Feminino , Humanos , Indústrias , Masculino , Pessoa de Meia-Idade , Pectinas/farmacocinética , Federação Russa , Fatores de Tempo , Vitaminas/farmacocinética , beta Caroteno/administração & dosagem , beta Caroteno/farmacocinética
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