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1.
Toxicol Res ; 37(4): 451-458, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34631502

RESUMO

Methylmercury is an environmental pollutant that induces potent neurotoxicity. We previously identified transcription factor 3 (TCF3) as a transcription factor that is activated in the brains of mice treated with methylmercury, and reported that methylmercury sensitivity was increased in cells in which TCF3 expression was suppressed. However, the mechanisms involved in the activation of TCF3 by methylmercury and in the reduction of methylmercury toxicity by TCF3 remained unclear. We found that treatment of mouse neuronal C17.2 cells with methylmercury increased TCF3 protein levels and promoted the binding of TCF3 to DNA consensus sequences. In cells treated with actinomycin D, a transcription inhibitor, an increase in TCF3 protein levels was also observed under methylmercury exposure. However, in the presence of cycloheximide, a translation inhibitor, methylmercury delayed the degradation of TCF3 protein. In addition, treatment with MG132, a proteasome inhibitor, increased TCF3 protein levels, and there was not significant increase in TCF3 protein levels by methylmercury under these conditions. These results suggest that methylmercury may activate TCF3 by increasing its levels through inhibition of TCF3 degradation by the proteasome. It has been previously reported that the induction of apoptosis in neurons is involved in methylmercury-induced neuronal damage in the brain. Although apoptosis was induced in C17.2 cells treated with methylmercury, this induction was largely suppressed by overexpression of TCF3. These results indicate that TCF3, which is increased in the brain upon exposure to methylmercury, may be a novel defense factor against methylmercury-induced neurotoxicity.

2.
Eur J Pharm Sci ; 168: 106047, 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34687899

RESUMO

Nintedanib (BIBF) is a biopharmaceutical classification system II (BCS II) drug that has a good therapeutic effect for the treatment of nonsmall cell lung cancer; however, it shows poor oral bioavailability due to low dissolution and intestinal absorption. This study aims to fabricate rod-shaped nanocrystals to enhance oral bioavailability by improving the dissolution and absorption of BIBF in the intestine. By prescription screening, BIBF nanocrystals (BIBF-NCs) with a particle size of 325.30 ± 1.03 nm and zeta potential of 32.70 ± 1.24 mV were fabricated by an antisolvent precipitation-ultrasound approach with a stabilizer of sodium carboxyl methyl cellulose (CMC-Na). BIBF-NCs exhibited a rod-shaped morphology by transmission electron microscopy (TEM). The results of powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC) showed that the crystal form of BIBF in BIBF-NCs was altered. The BIBF-NCs remarkably improved the saturation solubility and dissolution of BIBF compared with BIBF powder. According to the results of in situ single-pass intestinal perfusion (SPIP), BIBF-NCs showed improved absorption and membrane permeability, with Ka and Papp values in the jejunum of 0.21 ± 0.01 min-1 and (4.34 ± 0.11) × 10-4 cm/min, respectively. Further, the Ka and Papp values of BIBF-NCs were all reduced significantly after the addition of inhibitors colchicine, chlorpromazine and indomethacin, which demonstrated that BIBF-NCs could be absorbed by endocytosis mediated by caveolae and clathrin and micropinocytosis in the intestine. The cell evaluation results showed that BIBF-NCs could be taken up by macrophages and transported from Caco-2 monolayers. The in vivo pharmacokinetic results showed that the bioavailability of the BIBF-NCs was 2.51-fold higher than that of the BIBF solution (BIBF-Sol) after oral administration with a longer Tmax (4.50 ± 1.00 h vs. 2.60 ± 1.92 h). In summary, rod-shaped BIBF-NCs could significantly improve oral bioavailability through multiple intestinal absorption pathways.

3.
BMC Public Health ; 21(1): 1561, 2021 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-34404376

RESUMO

BACKGROUND: Published studies examining the association between childhood maltreatment (CM) and self-harm (SH) among adolescents have been accumulated. It is possible that resilience serves as a moderator or mediator in CM-SH association, nevertheless, this topic has never been thoroughly investigated. METHODS: In this population-based cross-sectional study, we surveyed 3146 students aged 10-17 in southwest China. The Childhood Trauma Questionnaire (CTQ), the Modified version of Adolescents Self-Harm Scale (MASHS), and the Resilience Scale for Chinese Adolescents (RSCA) were used to measure CM, SH, and resilience. Correlational analyses, hierarchical multivariate linear regression, and structural equation modeling (SEM) were performed to test the moderation and mediation of resilience in CM-SH association. RESULTS: Findings revealed that, resilience with its five dimensions, CM, and SH were significantly correlated with each other. Resilience partially moderated and mediated the association between CM and SH. Besides, among all dimensions of resilience, emotion regulation, interpersonal assistance, and family support presented the strongest mediation in CM-SH association. CONCLUSIONS: Our results highlight the importance of resilience in CM related SH among Chinese teenagers. Resilience-oriented intervention could be considered in SH intervention measures for adolescents who had experienced CM.


Assuntos
Maus-Tratos Infantis , Comportamento Autodestrutivo , Adolescente , Criança , China/epidemiologia , Estudos Transversais , Humanos , Comportamento Autodestrutivo/epidemiologia , Estudantes , Inquéritos e Questionários
4.
Int J Pharm ; 607: 121021, 2021 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-34416333

RESUMO

Poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) have attracted considerable interest in the medical community as a sustained-release drug delivery system for localized treatment. However, it is currently a grand challenge to simultaneously achieve low-dose drugs, stable and prolonged drug release, and long-term retention circumventing uptake by macrophages. Here, we construct a solvent-exchange in-situ depot system by incorporating progesterone (PRG) loaded PLGA NPs into a sucrose acetate isobutyrate (SAIB) and PLGA matrix for the long term treatment of Assisted Reproductive Technology (ART). The results showed that different solvent and PLGA contents could affect the drug release rate of PRG NPs-SAIB-PLGA in-situ depot system (PSPIDS). When DMSO was used as solvent with the addition of 8% PLGA to the depot, PSPIDS could achieve a constant drug release with no burst for 2 weeks in vitro. After a single intramuscular injection, such PSPIDS showed higher drug concentration and AUC (6773.0 ± 348.8 µg/L·h) over the entire 7-day testing period compared with the commercial multiple-day-dosing intramuscular PRG-oil solution (1914.5 ± 180.7 µg/L·h) in vivo. Importantly, PSPIDS could be administered at a dose of 3.65 mg/kg, which was one fourth of dose required for PRG-oil solution. The results demonstrate that PRG NPs could successfully achieve both reduced administered dosage and burst release, and therefore that PSPIDS is a promising long-acting composite system for hydrophobic drugs.


Assuntos
Nanopartículas , Progesterona , Portadores de Fármacos , Liberação Controlada de Fármacos , Ácido Láctico , Sacarose/análogos & derivados
5.
Front Pharmacol ; 12: 677014, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34276367

RESUMO

Arnebia decumbens (Vent.) Coss. et Kralik, A. euchroma (Royle) Johnst and A. guttata Bunge, three commonly used traditional Chinese medicinal plants have been widely used for the clinical treatment of inflammatory diseases caused by fungal, bacterial, oxidation, and other related pathogens. However, precise identification at the similar species level is usually challenging due to the influence of the source of medicinal materials, traditional ethnic medicine and medicinal habits. Here we developed a comprehensive and efficient identification system for three source spices of Arnebiae Radix based on DNA barcoding and HPLC fingerprinting. A total of 599 samples from thirty-five wild populations were collected and identified by using DNA barcodes of ITS2 regions, and the chemotypes of seven naphthoquinoneswere revealed by HPLC quantitative analysis including principal component analysis and hierarchical clustering analysis. Our results showed that the ITS2 sequences can distinguish three source spices of Arnebiae Radix from adulterants. However, it was difficult to identify them by HPLC-specific chromatograms combined with chemometric analysis. These results indicated that DNA barcoding was a more powerful method than HPLC fingerprinting for the identification of related species that were genetically similar. DNA barcoding analysis could be a promising and reliable tool to accurately confirm the identities of medicinal materials, especially for those whose sources are multiple and difficult to be identified by conventional chromatography.

6.
Healthcare (Basel) ; 9(6)2021 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-34205597

RESUMO

(1) Background: The effects of exercise-based cardiac rehabilitation (CR) on left ventricular function in patients with acute myocardial infarction (AMI) after percutaneous coronary intervention (PCI) are important but poorly understood. (2) Purpose: To evaluate the effects of an exercise-based CR program (exercise training alone or combined with psychosocial or educational interventions) compared with usual care on left ventricular function in patients with AMI receiving PCI. (3) Data sources, study selection and data extraction: We searched PubMed, WEB OF SCIENCE, EMBASE, EBSCO, PsycINFO, LILACS and Cochrane Central Register of Controlled Trials databases (CENTRAL) up to 12th June 2021. Article selected were randomized controlled trials and published as a full-text article. Meta-analysis was conducted with the use of the software Review manager 5.4. (4) Data synthesis: Eight trials were included in the meta-analysis, of which three trials were rated as high risk of bias. A significant improvement was seen in the exercise-based CR group compared with the control group regarding left ventricular ejection fraction (LVEF) (std. mean difference = 1.33; 95% CI:0.43 to 2.23; p = 0.004), left ventricular end-diastolic dimension (LVEDD) (std. mean difference = -3.05; 95% CI: -6.00 to -0.09; p = 0.04) and left ventricular end-systolic volume (LVESV) (std. mean difference = -0.40; 95% CI: -0.80 to -0.01; p = 0.04). Although exercise-based CR had no statistical effect in decreasing left ventricular end-systolic dimension (LVESD) and left ventricular end-diastolic volume (LVEDV), it showed a favorable trend in relation to both. (5) Conclusions: Exercise-based CR has beneficial effects on LV function and remodeling in AMI patients treated by PCI.

7.
Environ Res ; 201: 111597, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34214564

RESUMO

INTRODUCTION: Ambient air pollution might increase the risk of obesity; however, the evidence regarding the relationship between air pollution and obesity in comparable urban and rural areas is limited. Therefore, our aim was to contrast the effect estimates of varying air pollution particulate matter on obesity between urban and rural areas. METHODS: Four obesity indicators were evaluated in this study, namely, body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR). Exposure to ambient air pollution (e.g., particulate matter with aerodynamic diameters 1.0 µm [PM1], PM2.5, and PM10) was estimated using satellite-based random forest models. Linear regression and logistic regression models were used to assess the associations between air pollution particulate matter and obesity. Furthermore, the effect estimates of different air pollution particulates were contrasted between urban and rural areas. RESULTS: A total of 36,998 participants in urban areas and 31, 256 in rural areas were included. We found positive associations between long-term exposure to PM1, PM2.5, and PM10 and obesity. Of these air pollutants, PM2.5 had the strongest association. The results showed that the odds ratios (ORs) for general obesity were 1.8 (95% CI, 1.64 to 1.98) per interquartile range (IQR) µg/m3 increase in PM1, 1.89 (95% CI, 1.71 to 2.1) per IQR µg/m3 increase in PM2.5, and 1.74 (95% CI, 1.58 to 1.9) per IQR µg/m3 increase in PM10. The concentrations of air pollutants were lower in rural areas, but the effects of air pollution on obesity of rural residents were higher than those of urban residents. CONCLUSION: Long-term (3 years average) exposure to ambient air pollution was associated with an increased risk of obesity. We observed regional disparities in the effects of particulate matter exposure from air pollution on the risk of obesity, with higher effect estimates found in rural areas. Air quality interventions should be prioritized not only in urban areas but also in rural areas to reduce the risk of obesity.


Assuntos
Poluição do Ar , Poluição do Ar/efeitos adversos , China/epidemiologia , Humanos , Obesidade/epidemiologia , Obesidade/etiologia
9.
Int J Pharm ; 601: 120577, 2021 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-33839227

RESUMO

Resistance to platinum agents is a crucial challenge in the treatment of cancer using platinum drugs. To overcome the resistance of cells, the survivin protein is supposed to be decreased, since it has previously been found to be overexpressed in drug-resistant cancer cells in anti-apoptosis pathways, while the intracellular effective platinum accumulation should be increased. In the present work, a protamine/hyaluronic acid nanocarrier was used to load survivin siRNA with Pt(IV) loaded outside the coated polyglutamic acid (PGA) by chemical conjugation. The siRNA was released from the co-loaded nanoparticle prior to Pt(IV), in this way, the expression of survivin protein was effectively reduced, which, in turn, could avoid the anti-apoptosis of drug resistant cells. Here, Pt(IV) displayed a sustained release effect and gradually reduced to the toxic Pt(II) species, which reduced drug efflux and enhance apoptosis of the cancer cells. In vitro studies demonstrated that co-loaded nanoparticles resulted in similar cell killing performance in A549/DDP cells (cisplatin resistant) compared with non-siRNA loaded nanoparticles in A549 cells (cisplatin sensitive). NP-siRNA/Pt(IV) exhibited a greatly improved therapeutic effect (TIR, 82.46%) in a nude mice A549/DDP tumor model, with no serious adverse effects observed. Thus, co-loading of Pt(IV) and survivin siRNA nanoparticles could reverse cisplatin resistance and therefore has promising prospects for efficient cancer chemotherapy.


Assuntos
Antineoplásicos , Neoplasias Pulmonares , Nanopartículas , Pró-Fármacos , Animais , Antineoplásicos/farmacologia , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Camundongos , Camundongos Nus , Compostos Organoplatínicos/farmacologia , Pró-Fármacos/farmacologia , RNA Interferente Pequeno/farmacologia , Survivina/genética
10.
J Control Release ; 333: 269-282, 2021 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-33798664

RESUMO

Periodontitis is a chronic inflammation of the soft tissue surrounding and supporting the teeth, which causes periodontal structural damage, alveolar bone resorption, and even tooth loss. Its prevalence is very high, with nearly 60% of the global population affected. Hence, periodontitis is an important public health concern, and the development of effective healing treatments for oral diseases is a major target of the health sciences. Currently, the application of local drug delivery systems (LDDS) as an adjunctive therapy to scaling and root planning (SRP) in periodontitis is a promising strategy, giving higher efficacy and fewer side effects by controlling drug release. The cornerstone of successful periodontitis therapy is to select an appropriate bioactive agent and route of administration. In this context, this review highlights applications of LDDS with different properties in the treatment of periodontitis with or without systemic diseases, in order to reveal existing challenges and future research directions.


Assuntos
Periodontite , Sistemas de Liberação de Medicamentos , Humanos , Periodontite/tratamento farmacológico
11.
Artigo em Inglês | MEDLINE | ID: mdl-33712991

RESUMO

Lipid-polymer hybrid nanoparticles (LPNs) are promising drug delivery systems in various of disease treatment areas, particularly for cancer treatments. Here, a water-insoluble antitumor agent, hydroxycamptothecin (HCPT), was successfully incorporated into LPNs formed from polylactic-co-glycolic acid (PLGA), 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-(methoxy(polyethylene glycol)-2000) (DSPE-PEG2000), and lecithin, by a modified single emulsification-solvent evaporation method. Quality-by-design (QbD) strategy composed of Plackett-Burman and Box-Behnken designs were applied for optimizing HCPT-LPNs with desired properties. The optimized HCPT-loaded lipid-polymer hybrid nanoparticles (HCPT-LPNs) were on the nanoscale, with a final size of 220.9 nm, drug loading of 2.50%. HCPT-LPNs were highly stable in plasma and had pH- and drug loading-related sustained release characteristics. The in vitro cytotoxicity of HCPT-LPNs against MCF-7 and HepG2 cells showed that HCPT-LPNs had higher in vitro cytotoxicity than HCPT solution (HCPT-Sol) with reduced cell viability and IC50 values. In vivo pharmacokinetic assays demonstrated that the AUC of HCPT-LPNs was more than 3 times higher than that of HCPT-Sol after tail vein injection in SD rats. Tumor growth was significantly inhibited compared with HCPT-Sol after a single tail vein injection of HCPT-LPNs in murine LLC-GFP-luc lung cancer bearing mice at a dose of 6 mg/kg, without severe side effects. These results indicate that HCPT-LPNs are the promising drug delivery system for antitumor treatments.

12.
Nat Commun ; 12(1): 1595, 2021 03 11.
Artigo em Inglês | MEDLINE | ID: mdl-33707433

RESUMO

NH groups in proteins or nucleic acids are the most challenging target for chemical shift prediction. Here we show that the RNA base pair triplet motif dictates imino chemical shifts in its central base pair. A lookup table is established that links each type of base pair triplet to experimental chemical shifts of the central base pair, and can be used to predict imino chemical shifts of RNAs to remarkable accuracy. Strikingly, the semiempirical method can well interpret the variations of chemical shifts for different base pair triplets, and is even applicable to non-canonical motifs. This finding opens an avenue for predicting chemical shifts of more complicated RNA motifs. Furthermore, we combine the imino chemical shift prediction with NMR relaxation dispersion experiments targeting both 15N and 1HN of the imino group, and verify a previously characterized excited state of P5abc subdomain including an earlier speculated non-native G•G mismatch.


Assuntos
Pareamento de Bases/fisiologia , Mutação/genética , RNA/química , Repetições de Trinucleotídeos/genética , Sequência de Bases , Ressonância Magnética Nuclear Biomolecular
13.
Gen Psychiatr ; 34(2): e100246, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33782658

RESUMO

Background: There is an urgent need in clinical practice to measure the stress of parenting. The Caregiver Strain Questionnaire (CGSQ) was found to be useful to measure parenting stress, but it has not been validated among the Chinese population. Aims: To assess the reliability and construct validity of the Chinese version of CGSQ among Chinese parents. Methods: From 2016 to 2017, 266 parents (patient group) with a child having DSM-5-defined attention deficit hyperactivity disorder (ADHD) (n=107) or autism spectrum disorder (ASD) (n=159) and 268 parents of healthy children (control group) were recruited to the present study in Kunming, Yunnan province. All the parents were asked to fill out the Chinese version of CGSQ. We conducted exploratory factor analysis and confirmatory factor analysis (CFA) to verify construct validity of CGSQ in both patient and control groups. Cronbach's α coefficient as an index of internal consistency was assessed for each subscale. Fourteen days later, 23 subjects filled out the scale again. Intra-class correlation coefficient was calculated to evaluate the test-retest reliability. Results: (1) Cronbach's alpha of the global scale was 0.901 for the control group and 0.952 for the patient group. The test-retest reliability for the whole scale was 0.890; (2) CFA indicated that the three-factor model had better fitting indices compared with the two-factor model in both groups. Besides, the fitting indices in the patient group were more favourable than those of the control group, with χ2/df=1.564, Goodness-of-Fit Index=0.841, Comparative Fit Index=0.954, and root mean square error of approximation=0.065 for the patient group at three-factor model; (3) The caregiver strain of ASD parents was statistically higher than that of ADHD parents, and caregiver strain of ADHD parents was higher than that of control group. Conclusion: These findings provide initial evidence to support the construct validity and reliability of CGSQ as a parenting stress measurement tool for Chinese parents, especially for parents of children with ADHD or ASD.

14.
Health Qual Life Outcomes ; 19(1): 86, 2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33726779

RESUMO

BACKGROUND: Health education basing on patients' information-seeking styles can improve the effectiveness of health education and patients' health outcomes. The Miller Behavioral Style Scale (MBSS) is widely used to identify individual's information-seeking styles, but the Chinese version is lacking. The study aim was to translate and culturally adapt the MBSS into Chinese version and test the content validity, construct validity and internal consistency reliability of the Chinese version of MBSS (C-MBSS). METHODS: The forward-back-translation procedure was adopted in the translation of the MBSS. Content validity was assessed in a panel of experts. In a sample of 1343 individuals including patients, patients' caregivers, university students, and medical staff, reliability and construct validity were assessed using Cronbach's alpha coefficient and factor analysis. The measurement invariance across samples was tested using multigroup confirmatory factor analysis (MGCFA). Floor and ceiling effects were checked. RESULTS: The C-MBSS achieved conceptual and semantic equivalence with the original scale. The item-level content validity index (I-CVI) of each item ranged from 0.78 to 1, and the averaging scale-level content validity index (S-CVI/ Ave) was 0.95. The exploratory factor analysis resulted in 2-factor assumption for each hypothetical threat-evoking scenario. Confirmatory factor analysis demonstrated a good fit between theoretical model and data, which provided confirmatory evidence for the second-order factor structure of 2-factor solution (Monitoring and Blunting). The Cronbach's alpha coefficients for the Monitoring and Blunting sub-scales of the C-MBSS were 0.75 and 0.62 respectively. MGCFA results supported the measurement invariance for the Monitoring sub-scale of the C-MBSS across samples. No floor or ceiling effects occurred. CONCLUSIONS: This study indicates that the C-MBSS has good content and construct validity. The Monitoring sub-scale of the C-MBSS had acceptable internal consistency reliability while the Blunting sub-scale had unsatisfactory one, which suggest that the Monitoring sub-scale of the C-MBSS can be used to identify individuals' information-seeking styles in Chinese contexts across different populations.


Assuntos
Educação em Saúde/normas , Comportamento de Busca de Informação , Inquéritos e Questionários/normas , Adulto , China , Comparação Transcultural , Análise Fatorial , Feminino , Humanos , Masculino , Qualidade de Vida , Reprodutibilidade dos Testes , Traduções
15.
Artigo em Inglês | MEDLINE | ID: mdl-33531926

RESUMO

Flat warts are a common and recurrent skin disease that has no specific antiviral treatment. As an alternative or complementary therapy, fire needle therapy has been widely used in the treatment of flat warts. The objective of this study was to systematically evaluate the efficacy and safety of fire needle therapy for flat warts. Using the search terms "flat warts" and "fire needle," we searched the PubMed, Embase, Cochrane, China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, Chinese biomedical (SinoMed) database, and the China Science and Technology Journal databases for studies until March 12, 2020. Randomized controlled trials comparing fire needle therapies with conventional therapies were also included. We calculated the risk ratios (RR) and mean differences with a 95% confidence interval (CI). We analyzed 29 trials involving 2,666 patients. Results showed that the use of fire needle therapy alone may have a higher efficacy rate compared with that of an immunomodulator (RR = 1.11, 95% CI: 1.03 to 1.20, I 2 = 0%, P = 0.006; RR = 1.19, 95% CI: 1.03 to 1.37, I 2 = 70%, P = 0.02, respectively) or tretinoin (RR = 1.39, 95% CI: 1.25 to 1.55, I 2 = 0%, P < 0.00001), with a lower risk of blisters (P = 0.03) or erythema (P = 0.04), but with a higher risk of pigmentation (P = 0.02). We also determined the efficacy rate of fire needle therapy in combination with traditional Chinese medicine (RR = 1.16, 95% CI: 1.10 to 1.23, I 2 = 21%, P < 0.00001), immunomodulators (RR = 1.17, 95% CI: 1.07 to 1.28, I 2 = 33%, P = 0.0005), imiquimod (RR = 1.21, 95% CI: 1.04 to 1.42, P = 0.02), or as multidrug therapies (RR = 1.15, 95% CI: 1.07 to 1.24, I 2 = 0%, P = 0.0001) and found that the combination treatments could reduce recurrence rates (P < 0.00001) and provided a lower risk of desquamation (P = 0.006). In conclusion, fire needle therapy seems to be effective for flat warts, with a reduced incidence of adverse events, such as blisters, erythema, and desquamation, but may increase incidence of pigmentation.

16.
Int J Pharm ; 597: 120279, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33540020

RESUMO

To mask the bitterness of drug is profoundly important especially in children's medication. This study designed and investigated a quaternary enteric solid dispersion (QESD) by secondary hot-melt-extrusion. Erythromycin (EM) was chosen as a model drug. The optimal QESD contained enteric polymer HPMCP-55, plasticizer and water-soluble polymer copovidone VA64. Raman and Atomic force microscope has exploited that majority EM was distributed in VA64 matrix, nanometer-sized EM-VA64 system was entrapped within enteric continuous phase to form a solid emulsion-like structure. For the prepared QESD, EM released concentration was far less than bitterness threshold (7 µg/mL to 20 µg/mL) in artificial saliva within the first 30 s. And dissolution rate was increased by 10% in article intestine fluid, which dominated by water-soluble VA64. Stress testing after two months at high-humidity (75% RH) and high-temperature (60 °C) revealed, compared with traditional enteric SDs, the chemical degradation of EM was slowed down in QESD. Furthermore, hydrogen and salt bonds were respectively formed between EM and VA64 and between leaking EM and HPMCP-55, which increasing the system stability and taste-masking. The effect of masking bitter taste can be satisfied as well as enhance drug dissolution rate in the intestine, and formulation physicochemical stability during storage.


Assuntos
Portadores de Fármacos , Paladar , Criança , Composição de Medicamentos , Estabilidade de Medicamentos , Tecnologia de Extrusão por Fusão a Quente , Temperatura Alta , Humanos , Solubilidade
17.
J Control Release ; 333: 41-64, 2021 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-33450321

RESUMO

For the past few years, nanotechnology has provided a lot of new treatment opportunities for prostate cancer patients, and brilliant achievements have been acquired indeed. It not only prolonged circulation time in vivo but also increased bio-availability of drugs. Among them, nanoparticles with specificity ligand can be better targeted at prostate cancer, which improves the curative effect and reduces side effects. What's more, in terms of combined administration, the synergistic effect of chemotherapeutic drugs and hormones, or co-delivery two or more different drugs into the same delivery system, has achieved good therapeutic progress as well. In this paper, a comprehensive overview of nano-technology and the combination therapy for prostate cancer by pharmaceutical and clinical pharmaceutical strategies have been proposed to further appreciate and recommend the design and development of prostate cancer treatment.


Assuntos
Nanopartículas , Neoplasias da Próstata , Portadores de Fármacos/uso terapêutico , Sistemas de Liberação de Medicamentos , Humanos , Masculino , Neoplasias da Próstata/tratamento farmacológico
18.
J Clin Endocrinol Metab ; 106(5): e2096-e2105, 2021 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-33507274

RESUMO

CONTEXT: Loss of sleep or disturbance of sleep-wake cycles has been related to metabolic impairments. However, few studies have investigated the association between daily sleep duration and hyperuricemia. OBJECTIVE: We investigated daily sleep duration (daytime napping and nocturnal sleep) with hyperuricemia risk. METHODS: We cross-sectionally analyzed data from the China Multi-Ethnic Cohort (CMEC), Yunnan region. A total of 22 038 participants aged 30 to 79 years were recruited in 2018. Hyperuricemia was defined as serum uric acid (SUA) above 7.0 mg/dL in men and above 6.0 mg/dL in women. Outcomes were associations between daily sleep duration and hyperuricemia. RESULTS: We found that the longest daytime napping duration was associated with a higher risk of hyperuricemia in the crude model (odds ratio [OR] [95% CI], 2.22 [1.88-2.61], P < .001) and in a multivariable adjustment model (OR, 1.69; 95% CI, 1.41-2.01, P < .001) after adjusting for demographic, sleep habits, and metabolic risk factors. The association was moderately attenuated with additionally adjusted for serum creatinine (OR, 1.54; 95% CI, 1.28-1.86, P < .001). Longer daytime napping duration was also related to higher risk of hyperuricemia combined with metabolic syndrome (MetS). Respondents in the group with daytime napping duration greater than or equal to 90 minutes presented with a higher risk of hyperuricemia combined with MetS (OR, 1.39; 95% CI, 1.06-1.79; P < .001) in the fully adjusted model. We did not observe any relation between nocturnal sleep duration and risk of hyperuricemia in the study. CONCLUSION: Longer daytime napping duration (but not nocturnal sleep duration) was independently associated with risk of hyperuricemia in a Chinese population.


Assuntos
Hiperuricemia/epidemiologia , Síndrome Metabólica/epidemiologia , Transtornos do Sono-Vigília/fisiopatologia , China/epidemiologia , Estudos Transversais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Prognóstico , Fatores de Risco , Fatores de Tempo
19.
Pharmaceutics ; 13(2)2021 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-33498470

RESUMO

Breviscapine (BVP), a flavonoid compound, is widely used in the treatment of cardiovascular and cerebrovascular diseases; however, the low oral bioavailability and short half-life properties limit its application. The aim of this study was to investigate the three preparations for improving its oral bioavailability: nanosuspensions (BVP-NS), liposomes (BVP-LP) and phospholipid complexes (BVP-PLC). In vitro and in vivo results suggested that these three could all significantly improved the cumulative released amount and oral bioavailability compared with physical mixture, in which BVP-PLC was the most optimal preparation with the relative bioavailability and mean retention time of 10.79 ± 0.25 (p < 0.01) and 471.32% (p < 0.01), respectively. Furthermore, the influence of drug-lipid ratios on the in vitro release and pharmacokinetic behavior of BVP-PLC was also studied and the results showed that 1:2 drug-lipid ratio was the most satisfactory one attributed to the moderate-intensity interaction between drug and phospholipid which could balance the drug loading and drug release very well.

20.
AAPS PharmSciTech ; 22(1): 38, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33409712

RESUMO

The objective of this study was to encapsulate the poorly water-soluble drug TM-2 into polymer micelles using mPEG2k-b-PLA2.4k to increase its aqueous solubility and improve its therapeutic effect for liver cancer. Furthermore, in order to achieve long-term storage, the micelle solution was successfully freeze-dried. This study theoretically clarified the possibility of enhancing the water solubility of TM-2 using mPEG2k-b-PLA2.4k micelles as well as the protective effects of mixed lyoprotectants. Differential scanning calorimetry (DSC), X-ray diffraction (XRD), and scanning electron microscopy (SEM) were performed, which showed that the drug has a good affinity with the polymer (χ = 0.489) according to Flory-Huggins theory and that lyoprotectants reduced the crystallinity of PEG in mPEG2k-b-PLA2.4k and played a space-protective role in the lyophilization process. In vivo experiments showed that micellization could improve the drug bioavailability and give a high therapeutic effect with a tumor inhibition rate of 84.5% under the tolerated dose.


Assuntos
Antineoplásicos/química , Antineoplásicos/uso terapêutico , Micelas , Poliésteres/química , Poliésteres/uso terapêutico , Polietilenoglicóis/química , Polietilenoglicóis/uso terapêutico , Liofilização , Humanos , Neoplasias/tratamento farmacológico , Solubilidade
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