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1.
Int J Biol Macromol ; 262(Pt 1): 129998, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38336326

RESUMO

How to effectively improve the poor interfacial adhesion between polylactic acid/poly(butylene adipate-co-terephthalate) (PLA/PBAT) matrix and thermoplastic starch (TPS) is still a challenge. Therefore, this work aims to introduce a convenient method to enhance the performance of PLA/PBAT/TPS blend by melt reactive extrusion. Here, using 4,4'-methylene-bis(N,N-diglycidyl-aniline) (MBDG) containing four epoxy groups as a reactive compatibilizer, and respectively using 1-methylimidazole (MI) or triethylenediamine (TD) as a catalyzer, serial PLA/PBAT/TPS ternary bio-composites are successfully prepared via melt reactive extrusion. The results showed that, under the catalysis of organic base, especially MI, the epoxy groups of MBDG can effectively react with hydroxyl and carboxyl groups of PLA/PBAT and hydroxyl groups in TPS to form chain-expanded and cross-linked structures. The tensile strength of the composites is increased by 20.0 % from 21.1 MPa, and the elongation at break is increased by 182.4 % from 17.6 % owing to the chain extension and the forming of cross-linked structures. The molecular weight, thermal stability, crystallinity, and surface hydrophobicity of the materials are gradually improved with the increase of MBDG content. The melt fluidity of the composites is also improved due to the enhancement of compatibility. The obtained PLA/PBAT/TPS materials have the potential to be green plastic products with good properties.


Assuntos
Alcenos , Resinas Epóxi , Ácidos Ftálicos , Poliésteres , Adipatos , Amido
2.
Molecules ; 28(15)2023 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-37570605

RESUMO

Organic thioethers play an important role in the discovery of drugs and natural products. However, the green synthesis of organic sulfide compounds remains a challenging task. The convenient and efficient synthesis of 5-alkoxy-3-halo-4-methylthio-2(5H)-furanones from DMSO is performed via the mediation of 1,3-dibromo-5,5-dimethylhydantoin (DBDMH), affording a facile route for the sulfur-functionalization of 3,4-dihalo-2(5H)-furanones under transition metal-free conditions. This new approach has demonstrated the functionalization of non-aromatic Csp2-X-type halides with unique structures containing C-X, C-O, C=O and C=C bonds. Compared with traditional synthesis methods using transition metal catalysts with ligands, this reaction has many advantages, such as the lower temperature, the shorter reaction time, the wide substrate range and good functional group tolerance. Notably, DMSO plays multiple roles, and is simultaneously used as an odorless methylthiolating reagent and safe solvent.

3.
Afr Health Sci ; 23(3): 117-127, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38357142

RESUMO

Background: High rates of sexual violence ratios in low-income countries are recognized as a global public health problem. The incidence of violence against African women has been increasing. However, no study has systematically summarized the global prevalence of sexual violence against African woman. Methods: We conducted a comprehensive search of PubMed, Embase and Web of Science, databases from their inception through January 2021 for pertinent studies on reporting the prevalence of sexual violence against African women. We included observational studies. The prevalence rate was estimated using a random-effects meta-analysis. The heterogeneity was evaluated using I2 statistic. Differences by study level characteristics were estimated through subgroup analysis and meta-regression. Results: A total of 9 cross-sectional studies were included (a total of 9,030 participants). The pooled sexual violence rate was 0.33 (95% CI = 0.23-0.42). Subgroup analyses found that there was a higher rates of sexual violence against pregnant woman in east Africa (0.41, 95% CI = 0.24-0.58), pregnant (0.42, 95% CI = 0.05-0.80), and interview (0.40, 95% CI = 0.01-0.78). The analysis found that the major sexual violence types were the physical violence (0.19, 95% CI = 0.07-0.31), psychological violence (0.36, 95% CI = 0.11-0.61), sexual assault (0.25, 95% CI = 0.02-0.47). Conclusions: Nearly one out of every three (33%) African woman around the world has been a victim of sexual violence in their life. This current study investigated the status and characteristics of sexual violence against women, which could provide an important reference for the African health care provider. Assessing this problem against African women helps government officials, policy makers, program designers and non-governmental organizations to design prevention and controlling strategies.


Assuntos
Violência de Gênero , Delitos Sexuais , Feminino , Humanos , Gravidez , África Oriental , Estudos Transversais , Gestantes , Prevalência , Estudos Observacionais como Assunto
4.
Chinese Journal of School Health ; (12): 659-663, 2023.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-973933

RESUMO

Objective@#To explore the correlation between non suicidal self injury(NSSI) behaviors and depressive symptoms in adolescents and to provide a theoretical basis for improvement of adolescent physical and mental health.@*Methods@#A total of 8 102 adolescents aged 12-17 years were selected by random cluster sampling method in Shanghai, Urumqi, Changsha and Kunming, using the Center for Epidemiologic Studies Depression Scale (CES-D) and the Adolescent Non Suicidal Self Injurious Behavior Assessment Questionnaire. Depressive symptoms and the occurrence of NSSI behaviors were assessed. The relationship between NSSI behaviors and depressive symptoms was analyzed using Chi square test, one way analysis and Logistic regression analysis.@*Results@#The overall detection rate of NSSI in adolescents, 24.6%, with a significantly lower detection rate in boys (23.1%) than in girls (26.2%) ( χ 2=10.97, P <0.05), and 24.7%, 24.6% in the middle school and high school segments, respectively, but the difference was not statistically significant ( χ 2=0.01, P >0.05). The overall detection rate of adolescent depressive symptoms was 49.7 % in the group with NSSI and 17.7% in the group without NSSI, with statistically significant differences ( χ 2=808.80, P < 0.01 ). The detection rates of adolescent depressive symptoms in the group with NSSI (male:44.0%, female:54.7%, middle school:49.6%, high school:49.8%) and the group without NSSI (male:14.2%, female:21.4%, middle school:14.3%, high school: 21.0 %) were statistically significant by sex and age groups ( χ 2=385.58, 412.44, 520.60, 313.78, P <0.01). Logistic regression models, after adjusting for gender and age, the risk for depressive symptoms was 2.65 times (95% CI =2.27-3.09) and 7.28 times (95% CI = 6.34- 8.37) more frequently in adolescents with episodic self injurious behavior and frequent self injurious behavior, respectively, compared to those without self injurious behavior. The association between NSSI status and depressive symptoms did not show sex differences ( P >0.05).@*Conclusion@#Adolescent NSSI behavior is positively associated with depressive symptoms, the attention should be paid to adolescent physical and mental health to reduce the occurrence of NSSI.

5.
Acta Pharmaceutica Sinica ; (12): 1685-1692, 2023.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-978727

RESUMO

Long-acting analgesia is a common clinical treatment method after surgery. The slow-release injection with long-acting analgesia has the advantages of less medication frequency and stable effect. In this study, the analgesic drug lappaconitine hydrobromide lyotropic liquid crystal injection was prepared, and its sustained release mechanism, drug release and pharmacodynamic characteristics were evaluated. The results of polarizing microscope and freeze-transmission electron microscope showed that the lyotropic liquid crystal injection of the liquid crystal precursor preparation of lappaconitine hydrobromide could be obtained by the combination of glycerol monooleate (GMO) and soybean lecithin (SPC) in different proportions. The results of dissolution study in vitro showed that the drug release rate of different forms of liquid crystal preparations was layered liquid crystal > cubic liquid crystal > hexagonal liquid crystal. The mathematical model fitting results of the release data showed that the external release of layered liquid crystal, cubic liquid crystal and hexagonal liquid crystal conforms to the Ritger-Peppas model, and the release mechanism was Fick diffusion. The results of pharmacodynamics study in vivo showed that the analgesic effect of lappaconitine hydrobromide lyotropic liquid crystal injection lasted for 3 days, and there was no abnormality in the incision and local tissue, showing good safety and tolerance. The study on drug release and elimination process of the in vivo gel repository showed that lappaconitine hydrobromide could be completely released from the lyotropic liquid crystal 3 days after administration, and the sustained-release materials could be gradually eliminated locally. All animal experiments were approved by the Experimental Animal Ethics Committee of the Shanghai Institute of Materia Medica, Chinese Academy of Sciences (No. 2021-08-GY-61) and the experiments were conducted in accordance with the relevant guiding principles and regulations. The lyotropic liquid crystal injection of lappaconitine hydrobromide prepared in this study presented a solution state at room temperature, and underwent phase transition in contact with the body fluid at the administration site, formed a drug depot and exerted a slow drug release effect. This preparation can reduce systemic toxicity, prolong the duration of analgesia, reduce the number of administrations, improve the compliance of postoperative patients, and provide a reference for the design of long-term sustained release analgesic preparations.

6.
Acta Pharmaceutica Sinica B ; (6): 1460-1472, 2022.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-929368

RESUMO

Transporters are traditionally considered to transport small molecules rather than large-sized nanoparticles due to their small pores. In this study, we demonstrate that the upregulated intestinal transporter (PCFT), which reaches a maximum of 12.3-fold expression in the intestinal epithelial cells of diabetic rats, mediates the uptake of the folic acid-grafted nanoparticles (FNP). Specifically, the upregulated PCFT could exert its function to mediate the endocytosis of FNP and efficiently stimulate the traverse of FNP across enterocytes by the lysosome-evading pathway, Golgi-targeting pathway and basolateral exocytosis, featuring a high oral insulin bioavailability of 14.4% in the diabetic rats. Conversely, in cells with relatively low PCFT expression, the positive surface charge contributes to the cellular uptake of FNP, and FNP are mainly degraded in the lysosomes. Overall, we emphasize that the upregulated intestinal transporters could direct the uptake of ligand-modified nanoparticles by mediating the endocytosis and intracellular trafficking of ligand-modified nanoparticles via the transporter-mediated pathway. This study may also theoretically provide insightful guidelines for the rational design of transporter-targeted nanoparticles to achieve efficient drug delivery in diverse diseases.

7.
iScience ; 24(6): 102518, 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34142032

RESUMO

The bio-based lactic acid (LA) and the common metal ion chelating agent iminodiacetic acid (IDA) are used to design and prepare a polymeric sustained-release Pb2+ chelating agent by a brief one-step reaction. After the analysis on theoretical calculation for this reaction, poly(lactic acid-iminodiacetic acid) [P(LA-co-IDA)] with different monomer molar feed ratios is synthesized via direct melt polycondensation. P(LA-co-IDA) mainly has star-shaped structure, and some of them have two-core or three-core structure. Thus, a possible mechanism of the polymerization is proposed. The degradation rate of P(LA-co-IDA)s can reach 70% in 4 weeks. The change of IDA release rate is consistent with the trend of the degradation rate, and the good Pb2+ chelating performance is confirmed. P(LA-co-IDA) is expected to be developed as a lead poisoning treatment drug or Pb2+ adsorbent in the environment with long-lasting effect, and this research provides a new strategy for the development of such drugs.

8.
PLoS One ; 16(4): e0248870, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33793576

RESUMO

Since ionizing radiation has showed the dramatic effect to kill the cancer cells through direct DNA damage as well as triggering anti-cancer immune responses including induction of NKG2D ligands, it has used for long time to treat many cancer patients. However, it has been known that radiotherapy might promote the remnant cancer cells to escape immune system and metastasis. One of the suggested ways of immune evasion is induction of a ligand for programmed death-1 (PD-L1) in head and neck cancer, bladder cancer and lung cancer cells which engages the receptor, programmed death-1 (PD-1) in immune cells. PD-1/PD-L1 axis transduces the inhibitory signal and suppresses the adaptive immunity. However, their role in innate immunity remains poorly understood. Therefore, we investigated whether ionizing radiation could change the expression of PD-L1 in malignant melanoma cells and the receptor, programmed death-1 (PD-1), in NK-92 cells. Surface PD-L1 levels on melanoma cells were increased by ionizing radiation in a dose-independent manner but the level of PD-L1 was not changed significantly in NK-92 cells. Radiation-induced PD-L1 suppressed the activity of the NK-92 cells against melanoma cells despite of upregulation of NKG2D ligands. Furthermore, activated NK cells had high level of PD-1 and could not kill PD-L1+ melanoma cells effectively. When we used PD-L1 inhibitor or silenced PD-L1 gene, inhibited PD-1/PD-L1 axis reversed the activity of the suppressed NK cells. Through these results, we supposed that PD-1/PD-L1 blockade could enhance the immune responses of NK cells against melanoma cells after radiotherapy and might overcome the PD-L1 mediated radioresistance of cancer cells.


Assuntos
Antígeno B7-H1/metabolismo , Melanoma , Receptor de Morte Celular Programada 1/metabolismo , Linhagem Celular Tumoral , Humanos , Imunidade Celular , Células Matadoras Naturais , Melanoma/imunologia , Melanoma/radioterapia , Tolerância a Radiação
9.
Preprint em Inglês | bioRxiv | ID: ppbiorxiv-439275

RESUMO

Safe, economical and effective vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are needed to achieve adequate herd immunity and halt the pandemic. We have constructed a novel SARS-CoV-2 vaccine, CoVac501, which is a self-adjuvanting peptide vaccine conjugated with Toll-like receptor 7 (TLR7) agonists. The vaccine contains two immunodominant peptides screened from receptor-binding domain (RBD) and is fully chemically synthesized. And the vaccine has optimized nanoemulsion formulation, outstanding stability and safety. In non-human primates (NHPs), CoVac501 elicited high and persistent titers of RBD-specific and protective neutralizing antibodies (NAbs), which were also effective to RBD mutations. CoVac501 was found to elicit the increase of memory T cells, antigen-specific CD8+ T cell responses and Th1-biased CD4+ T cell immune responses in NHPs. More importantly, the sera from the immunized NHPs can prevent infection of live SARS-CoV-2 in vitro. One-Sentence SummaryA novel SARS-CoV-2 vaccine we developed, CoVac501, which is a fully chemically synthesized and self-adjuvanting peptides conjugated with TLR7 agonists, can induce high-efficient humoral and cellular immune responses against SARS-CoV-2.

10.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-885973

RESUMO

Based on the needs of healthcare system reform, Australia has implemented activity based funding(ABF) payment mode nationwide, and established the Independent Hospital Pricing Authority as the specific implementation agency in 2011. The main responsibilities and functions of the ABF payment mode covers pricing of medical services, classification of healthcare services, collection of clinical data and cost accounting of healthcare services. ABF payment mode presents outstanding advantages in promoting the capacity of healthcare service, maintaining fairness of healthcare service supplies and carrying out cooperation across different institutions. These efforts provide important references for China in its top-level design of payment method, pilot project of classification system, medical service items and price dynamic adjustment, informationization and information standardization construction among public hospitals.

11.
Preprint em Inglês | medRxiv | ID: ppmedrxiv-20142554

RESUMO

BackgroundAfter the outbreak of Coronavirus disease in 2019 (COVID-19), stringent lockdown measures were imposed in Wuhan between January 23, 2020 and April 8, 2020. To provide evidence on the post-lockdown risk of COVID-19 epidemic in Wuhan, the city government conducted a citywide nucleic acid screening of SARS-CoV-2 infection between May 14 and June 1, 2020. MethodsAll city residents aged [≥]6 years were potentially eligible to participate the screening programme. The rate of detection of asymptomatic infected cases was calculated, and their demographic and geographic distributions were investigated. ArcGIS 10.0 was used to draw a geographic distribution of asymptomatic infected persons. ResultsThe screening programme recruited a total of 9,899,828 persons (response rate, 92.9%). The screening found no newly confirmed patients with COVID-19, and identified 300 asymptomatic infected cases (detection rate 0.303/10,000). In addition, 107 of 34,424 previously recovered patients with a history of COVID-19 diagnosis were tested positive (relapse rate, 0.31%). Virus culture of SARS-CoV-2 was negative for all 300 asymptomatic cases and all 107 recovered COVID-19 patients. A total of 1,174 close contacts of asymptomatic cases were traced and all of them had a negative nucleic acid testing result. ConclusionsPrevalence of COVID-19 nucleic acid test positivity was very low in the Wuhan general population, in recovered cases and in contacts of asymptomatic cases, five to eight weeks after the end of lockdown. These findings help resolve concerns about the post-lockdown risk of COVID-19 epidemic, and promote the recovery of economy and normal social life in Wuhan.

12.
Preprint em Inglês | medRxiv | ID: ppmedrxiv-20120808

RESUMO

BackgroundSo far, there has been no published population study on the relationship between COVID-19 infection and publics risk perception, information source, knowledge, attitude and four non-pharmaceutical interventions(NPI: hand washing, proper coughing habits, social distancing and mask wearing) during the COVID-19 outbreak in China. MethodsAn online survey of 8158 Chinese adults between 22 February to 5 March 2020 was conducted. Bivariate associations between categorical variables were examined using Fisher exact test. We also explored the determinants of four NPIs as well as their association with COVID-19 infection using logistic regression. ResultsOf 8158 adults included, 57 (0.73%) were infected with COVID-19. The overwhelming majority of respondents showed a positive attitude (99.2%), positive risk perception (99.9%) and high knowledge levels that were among the strongest predictors of four highly adopted NPIs (hand washing:96.8%; proper coughing: 93.1%; social distancing:87.1%; mask wearing:97.9%). There was an increased risk of COVID-19 infection for those who not washing hands (2.28% vs 0.65%; RR=3.53: 95%CI: 1.53-8.15; P<0.009); not practicing proper coughing (1.79% vs 0.73%; RR=2.44: 95%CI: 1.15-5.15;P=0.026); not practicing social distancing (1.52% vs 0.58%; RR=2.63:95%CI:1.48 - 4.67; P=0.002); and not wearing a mask (7.41% vs 0.6%; RR=12.38:95%CI:5.81-26.36; P<0.001). For those who did practice all other three NPIs, wearing mask was associated with significantly reduced risk of infection compared to those who did not wear a mask (0.6% vs 16.7%; p=0.035). Similarly, for those who did not practice all or part of the other three NPIs, wearing mask was also associated with significantly reduced risk of infection. In a penalised logistic regression model including all four NPIs, wearing a mask was the only significant predictor of COVID-19 infection among four NPIs (OR=7.20; 95%CI:2.24-23.11; p<0.001). ConclusionsWe found high levels of risk perception, positive attitude, desirable knowledge as well as a high level of adopting four NPIs. The relevant knowledge, risk perception and attitude were strong predictors of adapting the four NPIs. Mask wearing, among four personal NPIs, was the most effective protective measure against COVID-19 infection with added preventive effect among those who practised all or part of the other three NPIs.

13.
Curr Microbiol ; 77(7): 1292-1300, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32140834

RESUMO

Characterizing soil bacterial community is important to understand microbial distribution affected by environmental factors. Here, we investigated the bacterial communities distributed from different location on Nanshazhou island, South China Sea. We collected and compared soil bacterial communities from central island, intertidal island, and inshore island. Results showed no difference in the bacterial richness and diversity for the soils from the three different locations. However, weighted and unweighted UniFrac distances analysis revealed that the three soil samples were clearly separated from each other. Five bacterial phyla, including Proteobacteria, Bacteroidetes, Verrucomicrobia, Spirochaetes and Tenericutes were more abundant in the inshore island sample; while Deinococcus-Thermus was more abundant in the intertidal island sample; and the central island sample had more abundant Gemmatimonadetes and Planctomycetes. Bacterial structure showed significantly positive relationships with organic matter content, but it was significantly negatively correlated with sodium content. Furthermore, a network analysis based on Spearman correlation coefficients showed that there were similar numbers of positive and negative correlations within the bacterial community of Nanshazhou island. Our results revealed that the soil bacterial communities in the three sampling sites were easily affected by environmental fluctuations.


Assuntos
Bactérias , Microbiota/genética , Microbiologia do Solo , Bactérias/classificação , Bactérias/genética , Biodiversidade , China , Ilhas , Oceanos e Mares
14.
Acta Pharmaceutica Sinica ; (12): 1549-1561, 2020.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-823320

RESUMO

Diabetes is characterized by hyperglycemia, resulting from insulin deficiency or resistance, or both. Insulin plays an irreplaceable role in the treatment of diabetes. Subcutaneous injection is the main route of insulin administration, but usually leads to poor compliance and many side effects. Oral insulin is safer and more convenient, which has always been the Holy Grail for people to explore. After oral administration, insulin is absorbed into the hepatic portal vein and transported to the liver, which can activate the normal physiological functions and reduce the risk of hypoglycemia, insulin resistance, and improve patient compliance. However, the gastrointestinal tract has multiple absorption barriers such as chemical barrier, enzyme barrier, and permeation barrier. Due to the physical and chemical properties of insulin, it is difficult to achieve desired oral bioavailability. This article reviews the recent attempts and progress in the field of oral administration of insulin driven by innovative drug delivery technologies and biomaterials, including structural modification, enzyme inhibitors, absorption enhancers, various nanoparticles, liposomes, microspheres, and even microorganisms. Some clinical researches on oral insulin are also introduced.

15.
Cell Cycle ; 18(20): 2674-2684, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31416388

RESUMO

This study aimed to investigate the role and underlying mechanism of exosomes secreted by oxidized low-density lipoprotein (oxLDL)-stimulated macrophages in the progression of atherosclerosis (AS). Exosomes from peripheral blood of AS patients or oxLDL-treated macrophages were co-cultured with human neutrophils. Neutrophil extracellular traps (NETs) were detected by immunofluorescence staining. The levels of inflammatory cytokines were quantified by enzyme-linked immunosorbent assay (ELISA). The expression levels of miR-146a and superoxide dismutase 2 (SOD2) were determined by quantitative real-time PCR (qRT-PCR) and western blot. The generation of intracellular reactive oxygen species (ROS) was observed by using dichlorofluorescin diacetate (DCFH-DA). ApoE-deficient mice were fed with high-fat diet (HFD) to induce AS. Atherosclerotic plaques were evaluated by Oil red O (ORO) and hematoxylin-eosin (HE) staining. Our results showed that miRNA-146a was enriched in serum-derived exosomes of AS patients and oxLDL-treated macrophage THP-1-derived exosomes. Importantly, exosomal miR-146a secreted by oxLDL-treated macrophages promoted ROS and NETs release via targeting SOD2. In addition, intravenous administration of oxLDL-treated THP-1 cells-derived exosomes into AS mice significantly deteriorated AS in vivo. Our findings indicate that exosomal miR-146a derived from oxLDL-treated macrophages promotes NETs formation via inducing oxidative stress, which might provide a novel scientific basis for the understanding of AS progression.


Assuntos
Aterosclerose/sangue , Exossomos/metabolismo , Armadilhas Extracelulares/metabolismo , Lipoproteínas LDL/farmacologia , Macrófagos/metabolismo , Neutrófilos/metabolismo , Idoso , Animais , Apolipoproteínas E/genética , Apolipoproteínas E/metabolismo , Aterosclerose/metabolismo , Técnicas de Cocultura , Citocinas/metabolismo , Progressão da Doença , Exossomos/ultraestrutura , Armadilhas Extracelulares/efeitos dos fármacos , Feminino , Humanos , Macrófagos/efeitos dos fármacos , Masculino , Camundongos , Camundongos Knockout , MicroRNAs/genética , MicroRNAs/metabolismo , Microscopia Eletrônica de Transmissão , Pessoa de Meia-Idade , Placa Aterosclerótica/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo
16.
Acta Pharmaceutica Sinica B ; (6): 107-117, 2019.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-774999

RESUMO

Increasing the degree of supersaturation of drugs and maintaining their proper stability are very important in improving the oral bioavailability of poorly soluble drugs by a supersaturated drug delivery system (SDDS). In this study, we reported a complex system of Soluplus-Copovidone (Soluplus-PVPVA) loaded with the model drug silybin (SLB) that could not only maintain the stability of a supersaturated solution but also effectively promote oral absorption. The antiprecipitation effect of the polymers on SLB was observed using the solvent-shift method. In addition, the effects of the polymers on absorption were detected by cellular uptake and transport experiments. The mechanisms by which the Soluplus-PVPVA complex promotes oral absorption were explored by dynamic light scattering, transmission electron microscopy, fluorescence spectra and isothermal titration calorimetry analyses. Furthermore, a pharmacokinetic study in rats was used to demonstrate the advantages of the Soluplus-PVPVA complex. The results showed that Soluplus and PVPVA spontaneously formed complexes in aqueous solution the adsorption of PVPVA on the hydrophilic-hydrophobic interface of the Soluplus micelle, and the Soluplus-PVPVA complex significantly increased the absorption of SLB. In conclusion, the Soluplus-PVPVA complex is a potential SDDS for improving the bioavailability of hydrophobic drugs.

17.
Acta Pharmaceutica Sinica B ; (6): 858-870, 2019.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-774937

RESUMO

Recently, liposomes have been widely used in cancer therapeutics, but their anti-tumor effects are suboptimal due to limited tumor penetration. To solve this problem, researchers have made significant efforts to optimize liposomal diameters and potentials, but little attention has been paid to liposomal membrane rigidity. Herein, we sought to demonstrate the effects of cholesterol-tuned liposomal membrane rigidity on tumor penetration and anti-tumor effects. In this study, liposomes composed of hydrogenated soybean phospholipids (HSPC), 1,2-distearoyl--glycero-3-phosphoethanolamine--[methoxy(polyethylene glycol)-2000] (DSPE-PEG) and different concentrations of cholesterol were prepared. It was revealed that liposomal membrane rigidity decreased with the addition of cholesterol. Moderate cholesterol content conferred excellent diffusivity to liposomes in simulated diffusion medium, while excessive cholesterol limited the diffusion process. We concluded that the differences of the diffusion rates likely stemmed from the alterations in liposomal membrane rigidity, with moderate rigidity leading to improved diffusion. Next, the tumor penetration and the anti-tumor effects were analyzed. The results showed that liposomes with moderate rigidity gained excellent tumor penetration and enhanced anti-tumor effects. These findings illustrate a feasible and effective way to improve tumor penetration and therapeutic efficacy of liposomes by changing the cholesterol content, and highlight the importance of liposomal membrane rigidity.

18.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-821300

RESUMO

Objective@#To explore the distribution characteristics of MTHFR gene polymorphism of Chinese Han population in Beijing, and analyze the differences of distribution of MTHFR gene polymorphism between Beijing area and the other parts of northern China. @*Methods@#MTHFR C677T gene was detected by PCR-gold magnetic particles chromatography. The distribution characteristics of MTHFR gene polymorphism of 3 945 healthy subjects from September 2014 to May 2018 detected in Peking Union Medical College Hospital were analyzed retrospectively. The distribution of MTHFR gene polymorphism in Chinese Han population in Beijing area was compared with the Han population of the other area from northern China by reviewing domestic and foreign literature databases. @*Results@#The frequencies of CC, CT and TT genotype of MTHFR C677T gene in the male population undergoing physical examination in Beijing were 23.3%, 50.5% and 26.2%, respectively, and the frequencies of C and T allele frequencies were 48.6% and 51.4%, respectively. The frequencies of CC, CT and TT genotype of MTHFR C677T gene in the female population were 22.7%, 49.4% and 27.9%, respectively, and the C and T allele frequencies were 47.4% and 52.6%, respectively. There was no difference in genotype frequency and allele freaaency between male and femal (P>0.05). The frequencies of CC, CT and TT genotypes and allele frequencies of MTHFR C677T gene in the population of Beijing area were significantly different from those of Heilongjiang, Jilin, Hebei, Shandong and Henan provinces (P<0.01). @*Conclusion@#There was no significant difference of polymorphism distribution of MTHFR C677T gene between male and female populations in Beijing. The distinct distribution characteristics of MTHFR gene in Beijing area should be presented.

19.
Acta Pharmaceutica Sinica B ; (6): 1145-1162, 2019.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-815863

RESUMO

Drug delivery systems (DDS) are defined as methods by which drugs are delivered to desired tissues, organs, cells and subcellular organs for drug release and absorption through a variety of drug carriers. Its usual purpose to improve the pharmacological activities of therapeutic drugs and to overcome problems such as limited solubility, drug aggregation, low bioavailability, poor biodistribution, lack of selectivity, or to reduce the side effects of therapeutic drugs. During 2015-2018, significant progress in the research on drug delivery systems has been achieved along with advances in related fields, such as pharmaceutical sciences, material sciences and biomedical sciences. This review provides a concise overview of current progress in this research area through its focus on the delivery strategies, construction techniques and specific examples. It is a valuable reference for pharmaceutical scientists who want to learn more about the design of drug delivery systems.

20.
Acta Pharmaceutica Sinica ; (12): 22-28, 2019.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-778664

RESUMO

The poor solubility of cyclosporine A (CsA) in water limits its oral absorption. We prepared CsA/ Soluplus/SDS complex, which can form CsA/Soluplus/SDS supersaturated micelles (CSS-SM) after hydration. Then, We further prepared CSS-SM osmotic pump tablets (CSS-SM-T). CSS-SM had a particle size of 156 nm, where in encapsulation efficiency and drug loading efficiency of CsA were 89.0% and 17.5%, respectively. CSS-SM-T achieved zero-level drug release in vitro. Pharmacokinetic data from Beagle dogs (all animal experiments were conducted under the guidelines approved by the Institutional Animal Care and Use Committee of the Shanghai Institute of Materia Medica, Chinese Academy of Sciences) indicated that CsA in the ordinary osmotic pump tablets was hardly absorbed after orally administered; despite slightly lower bioavailability [relative bioavailability: (85.1 ± 47.4) %] than that of Sandimmum Neoral, CSS-SM-T displayed lower fluctuations in CsA plasma concentration and obvious sustained-release characteristics in vivo, implying lower toxicity. Therefore, CSS-SM-T provides a new research idea for the design and development of oral sustained- and controlled-release preparations of poorly water-soluble drugs.

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