Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 139.258
Filtrar
1.
Anticancer Res ; 40(1): 551-556, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31892611

RESUMO

BACKGROUND/AIM: To investigate the effects of vitamin D3 supplementation on gut microbiota. PATIENTS AND METHODS: Twenty adults with vitamin D insufficiency/deficiency [25(OH)D <30 ng/ml] were enrolled and given 600, 4,000 or 10,000 IUs/day of oral vitamin D3 Stool samples were collected at baseline and 8 weeks for identifying gut microbiota using 16S rRNA gene amplification and sequencing. RESULTS: Baseline serum 25(OH)D was associated with increased relative abundance of Akkermansia and decreased relative abundance of Porphyromonas (p<0.05). After the intervention, we observed a dose-dependent increase in relative abundance of Bacteroides with a significant difference between the 600 IUs and the 10,000 IUs groups (p=0.027), and Parabacteroides with a significant difference between the 600 IUs and the 4,000 IUs groups (p=0.039). CONCLUSION: Increased serum 25(OH)D was associated with increased beneficial bacteria and decreased pathogenic bacteria. A dose-dependent increase in bacteria associated with decreased inflammatory bowel disease activity was observed after vitamin D3 supplementation.


Assuntos
Colecalciferol/administração & dosagem , Colecalciferol/farmacologia , Suplementos Nutricionais , Microbioma Gastrointestinal/efeitos dos fármacos , Administração Oral , Adulto , Bactérias/efeitos dos fármacos , Relação Dose-Resposta a Droga , Método Duplo-Cego , Humanos
2.
Angiology ; 71(1): 27-37, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31533437

RESUMO

We assessed the cardiovascular safety of long-term direct-acting oral anticoagulant (DOAC) treatment. A search of the medical literature was performed from inception until May 31, 2019. Inclusion criteria were (1) randomized trial that assessed the clinical efficacy and/or safety of 1 or more DOAC, (2) control group including oral anticoagulation and/or antiplatelet and/or placebo treatment, and (3) the incidence of acute coronary syndrome during follow-up was reported. Fixed-effect and random-effects models were applied. The analyzed outcomes were myocardial infarction (MI), major bleeding, and mortality. Twenty-eight randomized clinical trials (196 761 patients) were included. Rivaroxaban was associated with a 21% reduction in the relative risk of MI when compared to placebo (relative risk [RR]: 0.79 [95% credible interval, CrI: 0.65-0.94]) and a 31% reduction (RR: 0.70 [95% CrI: 0.53-0.89]) when compared to dabigatran. Apixaban resulted in 24% (RR: 0.76 [95% CrI: 0.58-0.99]) and vitamin K antagonists anticoagulation resulted in 19% (RR: 0.81 [95% CrI: 0.65-0.98]) risk reduction compared to dabigatran. The computed probability of being the first best choice of treatment was 61.8% for rivaroxaban. Cardiovascular safety shows considerable heterogeneity among oral anticoagulants. Treatment with rivaroxaban is associated with reduced rate of MI.


Assuntos
Anticoagulantes/administração & dosagem , Infarto do Miocárdio/prevenção & controle , Administração Oral , Anticoagulantes/efeitos adversos , Esquema de Medicação , Hemorragia/induzido quimicamente , Humanos , Infarto do Miocárdio/mortalidade , Meta-Análise em Rede , Fatores de Proteção , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
3.
Equine Vet J ; 52(1): 120-125, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30900298

RESUMO

BACKGROUND: There are no published studies on the pharmacokinetics of acetaminophen at the dosage used clinically (20 mg/kg), nor has the safety of multiple doses in horses been investigated. OBJECTIVE: Define the pharmacokinetic parameters of oral acetaminophen at 20 mg/kg in adult horses as a single dose, and twice daily for 14 days to assess the safety of multiple dosing. STUDY DESIGN: Pharmacokinetic study, multiple dose safety study. METHODS: Eight healthy Thoroughbred geldings were given acetaminophen (20 mg/kg; 500 mg tablets) orally as a single dose followed by doses every 12 h for 14 days. Serial blood samples were collected for determination of plasma acetaminophen concentrations using high performance liquid chromatography with ultraviolet detection. Serum biochemical analysis, gastroscopy and liver biopsy were examined during the safety study. RESULTS: Following a single dose, mean maximum concentration (Cmax ) was 16.61 µg/mL at 1.35 h (Tmax ), and drug concentration was below the lower limit of detection in most horses by 24 h. Elimination half-life (T1/2 ) was 2.78 h. No significant accumulation was noted following multiple doses. Average Cmax of acetaminophen following multiple oral dosing was 15.85 µg/mL, with a Tmax of 0.99 h and T1/2 of 4 h. Serum activities of sorbitol dehydrogenase were significantly decreased and total bilirubin concentrations were significantly increased following the last dose. No statistically significant changes were noted in gastroscopy scores. MAIN LIMITATIONS: Only one dose level (20 mg/kg) was studied, sample size was small and only a single breed and sex was used, with no pretreatment liver biopsies. CONCLUSION: This study described the pharmacokinetics of acetaminophen following single and multiple 20 mg/kg oral doses in adult horses and demonstrated the safety of acetaminophen with multiple oral dosing over 14 days. The summary is available in Portuguese - see Supporting information.


Assuntos
Acetaminofen/farmacocinética , Cavalos/metabolismo , Acetaminofen/administração & dosagem , Acetaminofen/efeitos adversos , Acetaminofen/sangue , Administração Oral , Animais , Esquema de Medicação , Meia-Vida , Cavalos/sangue , Masculino , Estatística como Assunto
4.
Kardiologiia ; 59(11): 76-83, 2019 Dec 11.
Artigo em Russo | MEDLINE | ID: mdl-31849302

RESUMO

Less onerous, compared with warfarin, treatment with direct oral anticoagulants (DOA) can lead to better adherence to treatment of patients with atrial fibrillation (AF). However, in a certain number of patients with AF, who were recommended by DOA, cardioembolic stroke recurs, which is largely due to the patients' failure to comply with medical recommendations. The appointment of DOA as first-line drugs does not guarantee a high adherence of patients with non-valvular AF. For elderly and old patients with AF and numerous comorbidities, the proposal of a simpler pharmacotherapy regimen is especially important. In a number of large modern studies performed in clinical practice, high adherence to rivaroxaban therapy has been established, which may be a result of taking this DOA 1 time per day, its safety and effectiveness.


Assuntos
Anticoagulantes/uso terapêutico , Fibrilação Atrial , Acidente Vascular Cerebral , Administração Oral , Idoso , Fibrilação Atrial/tratamento farmacológico , Dabigatrana , Humanos , Rivaroxabana , Varfarina
5.
Kardiologiia ; 59(12): 72-83, 2019 Dec 11.
Artigo em Russo | MEDLINE | ID: mdl-31849314

RESUMO

The review presents data on the prevalence of atrial fibrillation in patients on dialysis therapy. It is shown that dialysis-dependent patients with non-valve atrial fibrillation prognosis is extremely unfavorable, significantly increased risk of death due to both ischemic and hemorrhagic complications. Scales to assess the risk of thromboembolic and hemorrhagic complications in patients with atrial fibrillation on program dialysis are not validated. The lack of data from randomized clinical trials makes it much more difficult to choose anticoagulant therapy in patients with terminal stage of chronic kidney disease on dialysis who have undergone kidney transplantation. Therefore, the need for anticoagulant therapy and the choice of drugs in patients in this category should be made on the basis of a personalized multidisciplinary approach, taking into account comorbid pathology and the patient's preferences.


Assuntos
Fibrilação Atrial , Acidente Vascular Cerebral , Administração Oral , Anticoagulantes , Humanos , Prognóstico , Diálise Renal , Acidente Vascular Cerebral/tratamento farmacológico
6.
Zhongguo Zhong Yao Za Zhi ; 44(22): 4932-4939, 2019 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-31872603

RESUMO

This study is aimed to establish a method for the determination of baicalin,baicalin and purpurin in the plasma of rats after oral administration of Pudilan Xiaoyan Oral Liquid( PDL) by using liquid chromatography-mass spectrometry( LC-MS),analyze the pharmacokinetics of three components in rats,and investigate the effects of PDL on drug-metabolizing enzymes in rat liver. C18 column was used for liquid chromatography separation,with acetonitrile-water( containing 0. 2% formic acid) as the mobile phase for gradient elution. The mass spectrometry was detected by electrospray ion source( ESI) under multi-reaction monitoring mode( MRM),as well as positive and negative ion alternating mode. Plasma sample collection was performed by using an automatic blood collection meter for small animals. The pharmacokinetic parameters were calculated by Win Nonlin software. The total protein concentration of rat liver microsomes and the total enzyme content of CYP450 were determined by BCA method and spectrophotometry respectively. The methodological study in terms of linear range,recovery rate,precision and sample stability,was used to confirm that the LC-MS analysis method established in this experiment was simple,exclusive,accurate and reliable,and can meet the requirement of determining the content of baicalin,oroxindin and corynoline in plasma after PDL administration in rats. The drug-time curve showed that baicalin and oroxindin had a bimodal phenomenon,and the pharmacokinetic parameters indicated that baicalin,oroxindin and corynoline in PDL had certain drug-like properties. After 7 consecutive days of PDL administration,the rat liver coefficient,total liver microparticle protein and CYP450 enzyme content were increased,but there was no significant difference,indicating that PDL was less likely to develop drug-drug interaction based on CYP enzyme. The results of this experiment can provide reference for the research on in vivo efficacy and drug interaction of PDL as well as on its clinical application.


Assuntos
Medicamentos de Ervas Chinesas/farmacocinética , Espectrometria de Massas em Tandem , Administração Oral , Animais , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Fígado , Ratos , Reprodutibilidade dos Testes , Espectrometria de Massas por Ionização por Electrospray
7.
Kardiologiia ; 59(11S): 28-35, 2019 Nov 25.
Artigo em Russo | MEDLINE | ID: mdl-31884938

RESUMO

The thematic review presents modern solutions using oral anticoagulants with a focus on direct coagulation factor X inhibitors. It contains information about the pharmacodynamics and pharmacokinetics of apixaban and rivaroxaban against the background of different drug intake regimens - twice and once per day. There are shown studies of concentration dynamics and the corresponding functional response, measured using the integral method - the thrombin generation test, which is widely used in scientific research to describe hemostatic processes based on an objective quantitative assessment of the thrombin formation - a key coagulation cascade serine protease. The logical relationship between the pharmacodynamics of anticoagulant action and the clinical presentation of the effectiveness and safety of drugs is traced. The review provides links to actual literature and current clinical guidelines.


Assuntos
Inibidores do Fator Xa/uso terapêutico , Administração Oral , Anticoagulantes , Coagulação Sanguínea , Piridonas , Rivaroxabana , Trombina
8.
Wiad Lek ; 72(11 cz 2): 2214-2217, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31860839

RESUMO

In the last two decades a group of novel oral anticoagulants (NOACs) has been developed that directly block the activity of thrombin or activated factor X. No randomized controlled trials have been conducted to verify their efficacy and safety in patients with advanced chronic kidney disease (CKD) and atrial fibrillation. Few studies compared NOACs (dabigatran, rivaroxaban, apixaban, edoxaban) with classic anticoagulants in this unique group, and the results of these analyses remain controversial and inconclusive. Simple extrapolation of recommendations from the general population may be erroneous and lead to an increased risk of complications. Several controlled randomized trials with oral direct anticoagulants in hemodialysis patients are currently underway.


Assuntos
Anticoagulantes/uso terapêutico , Insuficiência Renal Crônica , Administração Oral , Hemorragia , Humanos , Rivaroxabana , Acidente Vascular Cerebral , Resultado do Tratamento
9.
Soins ; 64(841): 20-21, 2019 Dec.
Artigo em Francês | MEDLINE | ID: mdl-31864506

RESUMO

Oral chemotherapy is a therapy which is increasingly prescribed in outpatient care but which should not be trivialised. The patient must be given information and education to ensure compliance and awareness of the side effects to share with the care team as soon as they appear.


Assuntos
Neoplasias/tratamento farmacológico , Administração Oral , Humanos
10.
Anticancer Res ; 39(11): 6265-6271, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31704856

RESUMO

BACKGROUND/AIM: The present study aimed to examine the influence of antibiotics (AB) on the clinical outcomes of Japanese patients treated with immune check point inhibitors (ICIs) for metastatic renal cell carcinoma (RCC) patients. PATIENTS AND METHODS: A total of 31 patients with metastatic RCC treated with ICIs from November 2016 to April 2019 were retrospectively reviewed and analyzed. RESULTS: Five patients were treated with AB prior to ICIs treatment. Median progression free survival (PFS) of patients treated with AB vs. patients not treated with AB was 2.8 months and 18.4 months, respectively. The difference between PFS was statistically significant (p=0.0004). In multivariate analyses, AB use (p=0.0377) and presence of immune related adverse events (p=0.0042) were independent prognostic factors for PFS in association with ICIs therapy. CONCLUSION: The use of AB before ICIs treatment was a predictor of poor ICIs response in metastatic RCC.


Assuntos
Antibacterianos/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Administração Oral , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/administração & dosagem , Antineoplásicos Imunológicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Grupo com Ancestrais do Continente Asiático , Carcinoma de Células Renais/imunologia , Carcinoma de Células Renais/secundário , Feminino , Humanos , Ipilimumab/efeitos adversos , Ipilimumab/uso terapêutico , Japão , Neoplasias Renais/imunologia , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Nivolumabe/efeitos adversos , Nivolumabe/uso terapêutico , Prognóstico , Intervalo Livre de Progressão , Estudos Retrospectivos , Resultado do Tratamento
11.
Isr Med Assoc J ; 21(11): 743-746, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31713363

RESUMO

BACKGROUND: The use of oral midazolam as premedication to induce anxiolysis before surgical procedures under local anesthesia is widely accepted in plastic surgery. Rhinoplasty performed under local anesthesia is known to generate high levels of perioperative anxiety, thus the use of appropriate premedication is important. Oral midazolam has been shown to be safe in various procedures. However, the safety of oral midazolam before rhinoplasty has not been evaluated. OBJECTIVES: To evaluate the safety of premedication with oral midazolam prior to rhinoplasty by analyzing the intraoperative blood oxygen saturation levels as predictors of adverse respiratory events. METHODS: We retrospectively reviewed the anesthesia records of 62 patients who underwent rhinoplasty under local anesthesia and received premedication with oral midazolam for anxiolysis between March 2017 and December 2017. The median age of the patients was 25.4 years, and they were all classified as American Society of Anesthesiologists class 1. The patients received 10 mg midazolam hydrochloride orally 1 hour prior to the procedure. Oxygen blood saturation was monitored using a pulse oximeter and recorded every 15 minutes. RESULTS: All the patients maintained blood oxygen saturation levels above 95% (median peripheral capillary oxygen saturation 99%) on room air, and they did not require supplemental intraoperative oxygen. There were no transient hypoxemic events during and following the procedure. CONCLUSIONS: Our study confirmed the safety of oral midazolam premedication to reduce perioperative anxiety when performing rhinoplasty under local anesthesia.


Assuntos
Hipnóticos e Sedativos/administração & dosagem , Midazolam/administração & dosagem , Oxigênio/sangue , Rinoplastia , Administração Oral , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Oximetria , Pré-Medicação , Estudos Retrospectivos
12.
N Engl J Med ; 381(20): 1918-1928, 2019 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-31722152

RESUMO

BACKGROUND: The small-molecule phosphodiesterase 4 inhibitor apremilast modulates cytokines that are up-regulated in Behçet's syndrome. In a phase 2 trial involving patients with Behçet's syndrome, apremilast reduced the incidence and severity of oral ulcers. Data on the efficacy and safety of apremilast in patients with Behçet's syndrome who had active oral ulcers and had not previously received biologic agents are limited. METHODS: In a phase 3 trial, we randomly assigned, in a 1:1 ratio, patients who had Behçet's syndrome with active oral ulcers but no major organ involvement to receive either apremilast at a dose of 30 mg or placebo, administered orally, twice daily for 12 weeks, followed by a 52-week extension phase. The primary end point was the area under the curve (AUC) for the total number of oral ulcers during the 12-week placebo-controlled period (with lower values indicating fewer ulcers). There were 13 secondary end points, including complete response of oral ulcers, change from baseline in pain associated with oral ulcers, disease activity, and change from baseline in the Behçet's Disease Quality of Life score (range, 0 to 30, with higher scores indicating greater impairment in quality of life). Safety was also assessed. RESULTS: A total of 207 patients underwent randomization (104 patients to the apremilast group and 103 to the placebo group). The AUC for the number of oral ulcers was 129.5 for apremilast, as compared with 222.1 for placebo (least-squares mean difference, -92.6; 95% confidence interval [CI], -130.6 to -54.6; P<0.001). The change from baseline in the Behçet's Disease Quality of Life score was -4.3 points in the apremilast group, as compared with -1.2 points in the placebo group (least-squares mean difference, -3.1 points; 95% CI, -4.9 to -1.3). Adverse events with apremilast included diarrhea, nausea, and headache. CONCLUSIONS: In patients with oral ulcers associated with Behçet's syndrome, apremilast resulted in a greater reduction in the number of oral ulcers than placebo but was associated with adverse events, including diarrhea, nausea, and headache. (Funded by Celgene; ClinicalTrials.gov number, NCT02307513.).


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Síndrome de Behçet/tratamento farmacológico , Úlceras Orais/tratamento farmacológico , Inibidores da Fosfodiesterase 4/uso terapêutico , Talidomida/análogos & derivados , Administração Oral , Adulto , Anti-Inflamatórios não Esteroides/efeitos adversos , Área Sob a Curva , Síndrome de Behçet/complicações , Método Duplo-Cego , Feminino , Humanos , Masculino , Úlceras Orais/etiologia , Inibidores da Fosfodiesterase 4/efeitos adversos , Qualidade de Vida , Talidomida/efeitos adversos , Talidomida/uso terapêutico
13.
MMW Fortschr Med ; 161(Suppl 6): 15-23, 2019 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-31587168

RESUMO

BACKGROUND: Non-vitamin K-dependent oral anticoagulants (NOAC) have changed the management of patients with oral anticoagulation. This raises the question of which patients should preferably be anticoagulated with NOAC and which preferably with vitamin K antagonists (VKA). This discussion has so far been insufficiently conducted and often decided on a flat-rate basis in favor of the NOAC. METHOD: To clarify the question owhich form of anticoagulation - NOAC or VKA - is the best choice for patients with atrial fibrillation, an interdisciplinary team of experts met. RESULTS AND CONCLUSIONS: The experts discussed essential practical aspects of NOAC and VKA therapy. Based on typical clinical scenarios, they developed assistance, comments and tips on the differentiated use of oral anticoagulants in patients with atrial fibrillation. A criteria served amongst others practicability in daily medical practice, contraindications, side effects and interactions, but also the patient's desire. The advantages and disadvantages of therapy with VKA and NOAC were summarized in a table.


Assuntos
Anticoagulantes/uso terapêutico , Fibrilação Atrial , Vitamina K/antagonistas & inibidores , Administração Oral , Anticoagulantes/administração & dosagem , Fibrilação Atrial/tratamento farmacológico , Fibrinolíticos , Humanos , Modalidades de Fisioterapia
14.
Medicine (Baltimore) ; 98(42): e17323, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31626087

RESUMO

BACKGROUND: Non-adherence can be highlighted as one of the main contributors to the occurrence of adverse events in patients treated with warfarin. The usefulness of self-reporting measures of drug adherence could be improved by following psychometric properties in the development of the measurement scales. Thus, we aimed to describe the protocol of a systematic literature review designed to investigate and describe validated instruments used to assess adherence to warfarin therapy. METHODS: We will perform a systematic review will include observational and experimental studies involving the use of validated instruments to assess adherence to warfarin therapy. Dimensions of adherence raised by the selected studies will be extracted to be compared. We will systematically search electronic databases including MEDLINE, LILACS, EMBASE, and Cochrane Library using a comprehensive strategy from inception to June 31, 2019. Two reviewers will revise the literature independently using a standardized form and assess the potential bias. After the comparison of results, discrepancies will be solved after the analysis of a third reviewer. RESULT: The development of the present systematic will help to summarize and evaluate the validated instruments that have been previously published to assess adherence to warfarin therapy. CONCLUSION: This review will substantiate the discussion of relevant topics that should be assessed while providing care to patients taking warfarin. This knowledge will enable a comprehensive approach for healthcare professionals to improve treatment outcomes and the design of future investigations. REGISTRATION: The systematic review is registered in the PROSPERO international prospective register of systematic review (PROSPERO# CRD42019128324).


Assuntos
Anticoagulantes/uso terapêutico , Adesão à Medicação , Varfarina/uso terapêutico , Administração Oral , Humanos , Revisão Sistemática como Assunto , Estudos de Validação como Assunto
15.
Chem Commun (Camb) ; 55(89): 13362-13365, 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31631195

RESUMO

Rule-of-five parameters and membrane permeabilities have been routinely used to guide development of orally bioavailabile drugs. Here we compare enantiomeric pairs of cyclic hexapeptides with identical rule-of-five parameters and membrane permeabilities. For each enantiomeric pair, the isomer with more l- than d-amino acids is much more orally bioavailable in rats, more metabolically stable to rat liver microsomes, and cleared more slowly in vivo.


Assuntos
Peptídeos Cíclicos/metabolismo , Peptídeos Cíclicos/farmacocinética , Administração Oral , Animais , Disponibilidade Biológica , Microssomos Hepáticos/química , Microssomos Hepáticos/metabolismo , Conformação Molecular , Peptídeos Cíclicos/administração & dosagem , Ratos , Estereoisomerismo
18.
Int J Nanomedicine ; 14: 7743-7758, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31571874

RESUMO

Purpose: Peptide drugs have been used in therapy various diseases. However, the poor bioavailability of peptide drugs for oral administration has limited their clinical applications, on account of the acidic environment and digestive enzymes inside the human gastrointestinal tract. To enhance stability in the human gastrointestinal tract, bioavailability, and targeted drug delivery of peptide drugs through oral administration, a vitamin B12-modified amphiphilic sodium alginate derivative (CSAD-VB12) was synthesized. Materials and methods: A vitamin B12-modified amphiphilic sodium alginate derivative (CSAD-VB12) was synthesized via the N,N'-dicyclohexylcarbodiimide active method at room temperature, and then characterized using FTIR and 1H NMR spectroscopy. Insulin was used as a model peptide drug and the insulin-loaded CSAD-VB12 (CSAD-VB12/insulin) nanoparticles with negative zeta potentials were prepared in PBS (pH=7.4). Scanning electron microscopy was used to observe CSAD-VB12/insulin as spherical nanoparticles. The CSAD-VB12 derivatives and CSAD-VB12/insulin nanoparticles displayed nontoxicity towards the human colon adenocarcinoma (Caco-2) cells by CCK-8 test. Caco-2 cell model was used to measure the apparent permeability (Papp) of insulin, CSAD/insulin and CSAD-VB12/insulin. Furthermore, confocal was used to confirm the endocytosis of intestinal enterocytes. Type 1 diabetes mice were used to evaluate the intestinal absorption and retention effect of test nanoparticles. Results: They were observed as spherical nanoparticles in the size of 30-50 nm. The CSAD-VB12 derivatives and CSAD-VB12/insulin nanoparticles displayed nontoxicity towards the human colon adenocarcinoma (Caco-2) cells. Comparing with insulin and the CSAD/insulin nanoparticles, the CSAD-VB12/insulin nanoparticles exhibited higher permeation ability through intestinal enterocytes in the Caco-2 cell model. Oral administration of the CSAD-VB12/insulin nanoparticles to Type 1 diabetic mice yields higher intestinal retention effect, targeted absorption, and outstanding efficacy. Conclusion: CSAD-VB12 derivatives enhance the small intestinal absorption efficacy and retention of peptide by oral administration, which indicated that it could be a promising candidate for oral peptide delivery in the prospective clinical application.


Assuntos
Alginatos/química , Sistemas de Liberação de Medicamentos , Peptídeos/administração & dosagem , Preparações Farmacêuticas/administração & dosagem , Vitamina B 12/química , Administração Oral , Alginatos/síntese química , Animais , Células CACO-2 , Morte Celular/efeitos dos fármacos , Permeabilidade da Membrana Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Diabetes Mellitus Experimental/tratamento farmacológico , Liberação Controlada de Fármacos , Endocitose/efeitos dos fármacos , Feminino , Humanos , Insulina/administração & dosagem , Insulina/farmacologia , Insulina/uso terapêutico , Absorção Intestinal/efeitos dos fármacos , Masculino , Camundongos , Nanopartículas/química , Nanopartículas/ultraestrutura , Peptídeos/farmacologia , Peptídeos/uso terapêutico , Espectroscopia de Prótons por Ressonância Magnética , Espectroscopia de Infravermelho com Transformada de Fourier , Vitamina B 12/síntese química
19.
Int J Nanomedicine ; 14: 7095-7106, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31564867

RESUMO

Background: Norisoboldine (NOR), the main isoquinoline alkaloid constituent in Radix Linderae, was demonstrated to have an outstanding anti-arthritis activity. However, a poor oral bioavailability of NOR creates a barrier for its development and application. Methods: A new self-nanoemulsifying drug delivery system (SNEDDS) loaded with the phospholipid complex (PC) was designed to improve the oral bioavailability of NOR. NOR-PC was prepared by solvent evaporation method with a mixture of phospholipid and NOR at a mass ratio of 3:1. The property of PC is to improve the liposolubility of NOR, and made PC embedded in the drug delivery system. The physicochemical property of NOR-PC was characterized by differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FT-IR). According to the ability to dissolve NOR-PC, the oil and cosurfactant were chosen. The surfactant was selected based on its emulsification efficiency in SNEDDS. Pseudo-ternary phase diagram was created to select the best formulation of NOR-PC-SNEDDS, and the pharmacokinetic parameters were detected in rats. In addition, intestinal lymphatic transport and liver microsome experiment were studied to gain insight into the mechanism for NOR-PC-SNEDDS increasing the oral bioavailability of NOR. Results: Solubility detection showed that the PC significantly improved the liposolubility of NOR. NOR-PC-SNEDDS was prepared using NOR-PC, Ethyl oleate, Labrasol, Cremophor EL and transcutol HP at a weight ratio of 1:2:3.36:2.24:2.4 (w/w/w/w/w). The particle size and zeta potential of NOR-PC-SNEDDS were 36.72±1.47 nm and -4.91±0.49 mV after dilution with distilled water at a ratio of 1:50 (w/w). The absolute bioavailability of NOR in the NOR-PC-SNEDDS group significantly increased and the value was 372% in relative to NOR group. Further studies indicated that NOR-PC-SNEDDS promoted the oral bioavailability of NOR by enhancing intestinal lymphatic absorption and inhibiting Phase II metabolism of NOR. Conclusion: These findings suggested that NOR-PC-SNEDDS was able to promote the oral bioavailability of NOR, which provided a foundation for the further development and application of NOR.


Assuntos
Absorção Fisiológica , Alcaloides/farmacologia , Sistemas de Liberação de Medicamentos , Emulsões/química , Nanopartículas/química , Fosfolipídeos/química , Administração Oral , Alcaloides/sangue , Alcaloides/química , Alcaloides/farmacocinética , Animais , Varredura Diferencial de Calorimetria , Intestinos/fisiologia , Sistema Linfático/fisiologia , Masculino , Desintoxicação Metabólica Fase II , Microssomos Hepáticos/efeitos dos fármacos , Microssomos Hepáticos/metabolismo , Transição de Fase , Ratos Sprague-Dawley , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier , Tensoativos/química , Termodinâmica , Fatores de Tempo
20.
Int J Nanomedicine ; 14: 7291-7306, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31564878

RESUMO

Purpose: The aims of this study were to prepare a baicalein self-microemulsion with baicalein-phospholipid complex as the intermediate (BAPC-SMEDDS) and to compare its effects with those of conventional baicalein self-microemulsion (CBA-SMEDDS) on baicalein oral absorption and lymphatic transport. Methods: Two SMEDDS were characterized by emulsifying efficiency, droplet size, zeta potential, cloud point, dilution stability, physical stability, and in vitro release and lipolysis. Different formulations of 40 mg/kg baicalein were orally administered to Sprague-Dawley rats to investigate their respective bioavailabilities. The chylomicron flow blocking rat model was used to evaluate their lymphatic transport. Results: The droplet sizes of BAPC-SMEDDS and CBA-SMEDDS after 100x dilution were 9.6±0.2 nm and 11.3±0.4 nm, respectively. In vivo experiments indicated that the relative bioavailability of CBA-SMEDDS and BAPC-SMEDDS was 342.5% and 448.7% compared to that of free baicalein (BA). The AUC0-t and Cmax of BAPC-SMEDDS were 1.31 and 1.87 times higher than those of CBA-SMEDDS, respectively. The lymphatic transport study revealed that 81.2% of orally absorbed BA entered the circulation directly through the portal vein, whereas approximately 18.8% was transported into the blood via lymphatic transport. CBA-SMEDDS and BAPC-SMEDDS increased the lymphatic transport ratio of BA from 18.8% to 56.2% and 70.2%, respectively. Therefore, self-microemulsion not only significantly improves oral bioavailability of baicalein, but also increases the proportion lymphatically transported. This is beneficial to the direct interaction of baicalein with relevant immune cells in the lymphatic system and for proper display of its effects. Conclusion: This study demonstrates the oral absorption and lymphatic transport characteristics of free baicalein and baicalein SMEDDS with different compositions. This is of great significance to studies on lymphatic targeted delivery of natural immunomodulatory compounds.


Assuntos
Absorção Fisiológica , Sistemas de Liberação de Medicamentos , Emulsões/química , Flavanonas/administração & dosagem , Flavanonas/farmacologia , Fosfolipídeos/química , Administração Oral , Animais , Disponibilidade Biológica , Composição de Medicamentos , Sistema Linfático/efeitos dos fármacos , Sistema Linfático/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley , Solubilidade
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA