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1.
Stroke ; : STROKEAHA119025732, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31409268

RESUMO

Background and Purpose- In patients with symptomatic intracranial atherosclerotic stenosis, identifying the underlying stroke mechanisms may inform secondary prevention. We aimed to propose reproducible classification criteria for stroke mechanisms based on routine neuroimaging in symptomatic intracranial atherosclerotic stenosis and explore their clinical implications. Methods- We recruited patients with acute ischemic stroke attributed to 50% to 99% intracranial atherosclerotic stenosis in anterior circulation from 2 centers. Two investigators independently classified probable stroke mechanisms as parent artery atherosclerosis occluding penetrating artery, artery-to-artery embolism, hypoperfusion, and mixed mechanisms, with prespecified criteria based on infarct topography and magnetic resonance/computed tomography angiography. These stroke mechanisms were correlated with features of the patients at baseline and recurrent ischemic stroke in the same territory or relevant transient ischemic attack within 1 year. Results- Among 153 patients recruited, the most common stroke mechanisms were isolated hypoperfusion (35.3%) and mixed mechanism of artery-to-artery embolism and hypoperfusion (37.3%) that was associated with higher incidence of dyslipidemia (P=0.045) and hypertension (P=0.033) than patients with other stroke mechanisms. The proposed criteria showed substantial to excellent intrarater and interrater reproducibilities (κ, 0.791-0.908). Overall, 31 patients received interventional treatment of the diseased intracranial artery; 122 received medical treatment, among whom a mixed mechanism of artery-to-artery embolism and hypoperfusion at baseline was associated with higher risk of ischemic stroke in the same territory within 1 year (24.4% versus 7.8%; hazard ratio, 3.40; 95% CI, 1.25-9.20; log-rank P=0.010) than other mechanisms combined. Conclusions- Artery-to-artery embolism and hypoperfusion commonly coexist in ischemic stroke attributed to intracranial atherosclerotic stenosis, which may be associated with higher risk of stroke relapse.

2.
Angew Chem Int Ed Engl ; 58(34): 11879-11885, 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31210375

RESUMO

Self-assembled nanostructures of rod-like molecules are commonly limited to nematic or layered smectic structures dominated by the parallel arrangement of the rod-like components. Distinct self-assembly behavior of four categories of dendritic rods constructed by placing a tri(hydroxy) group at the apex of dendritic oligo-fluorenes is observed. Designed hydrogen bonding and dendritic architecture break the parallel arrangement of the rods, resulting in molecules with specific (fan-like or cone-like) shapes. While the fan-shaped molecules tend to form hexagonal packing cylindrical phases, the cone-shaped molecules could form spherical motifs to pack into various ordered structures, including the Frank-Kasper A15 phase and dodecagonal quasicrystal. This study provides a model system to engineer diverse supramolecular structures by rod-like molecules and sheds new light into the mechanisms of the formation of unconventional spherical packing structures in soft matter.

3.
Ann Neurol ; 85(5): 752-764, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30840312

RESUMO

OBJECTIVE: To investigate whether hemodynamic features of symptomatic intracranial atherosclerotic stenosis (sICAS) might correlate with the risk of stroke relapse, using a computational fluid dynamics (CFD) model. METHODS: In a cohort study, we recruited patients with acute ischemic stroke attributed to 50 to 99% ICAS confirmed by computed tomographic angiography (CTA). With CTA-based CFD models, translesional pressure ratio (PR = pressurepoststenotic /pressureprestenotic ) and translesional wall shear stress ratio (WSSR = WSSstenotic - throat /WSSprestenotic ) were obtained in each sICAS lesion. Translesional PR ≤ median was defined as low PR and WSSR ≥4th quartile as high WSSR. All patients received standard medical treatment. The primary outcome was recurrent ischemic stroke in the same territory (SIT) within 1 year. RESULTS: Overall, 245 patients (median age = 61 years, 63.7% males) were analyzed. Median translesional PR was 0.94 (interquartile range [IQR] = 0.87-0.97); median translesional WSSR was 13.3 (IQR = 7.0-26.7). SIT occurred in 20 (8.2%) patients, mostly with multiple infarcts in the border zone and/or cortical regions. In multivariate Cox regression, low PR (adjusted hazard ratio [HR] = 3.16, p = 0.026) and high WSSR (adjusted HR = 3.05, p = 0.014) were independently associated with SIT. Patients with both low PR and high WSSR had significantly higher risk of SIT than those with normal PR and WSSR (risk = 17.5% vs 3.0%, adjusted HR = 7.52, p = 0.004). INTERPRETATION: This work represents a step forward in utilizing computational flow simulation techniques in studying intracranial atherosclerotic disease. It reveals a hemodynamic pattern of sICAS that is more prone to stroke relapse, and supports hypoperfusion and artery-to-artery embolism as common mechanisms of ischemic stroke in such patients. Ann Neurol 2019;85:752-764.

4.
Small ; 15(15): e1900427, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30844151

RESUMO

Micro-/nanomotors are widely used in micro-/nanoprocessing, cargo transportation, and other microscale tasks because of their ability to move independently. Many biological hybrid motors based on bacteria have been developed. Magnetotactic bacteria (MTB) have been employed as motors in biological systems because of their good biocompatibility and magnetotactic motion in magnetic fields. However, the magnetotaxis of MTB is difficult to control due to the lack of effective methods. Herein, a strategy that enables control over the motion of MTB is presented. By depositing synthetic Fe3 O4 magnetic nanoparticles on the surface of MTB, semiartificial magnetotactic bacteria (SAMTB) are produced. The overall magnetic properties of SAMTB, including saturation magnetization, residual magnetization, and blocking temperature, are regulated in a multivariate and multilevel fashion, thus regulating the magnetic sensitivity of SAMTB. This strategy provides a feasible method to manoeuvre MTB for applications in complex fluid environments, such as magnetic drug release systems and real-time tracking systems. Furthermore, this concept and methodology provide a paradigm for controlling the mobility of micro-/nanomotors based on natural small organisms.

5.
J Am Chem Soc ; 141(8): 3366-3370, 2019 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-30739439

RESUMO

Exchange coupled bimagnetic core/shell nanoparticles are promising for emerging multiferroic and spintronic technologies compared with traditional, single-phase materials, as they deliver numerous appealing effects, such as large exchange bias, tailored coercivities, and tunable blocking temperatures. However, it remains a challenge to manipulate their magnetic properties via exchange coupling due to the lack of a straightforward method that enables the general preparation of desired composites. Here we report a robust and general one-pot approach for the synthesis of different kinds of bimagnetic core/shell nanostructures (BMCS NSs). The formation of highly crystalline and monodisperse BMCS NSs adopted a self-adaptive sequential growth, circumventing the employment of complex temperature control and elaborate seeded growth techniques. As a result of large lattice misfit, the presence of interfacial imperfections as an extra source of anisotropy induced diverse exchange coupling interactions in ferro-ferrimagnetic and ferro-antiferromagnetic systems, which had great effects on the improvement of the magnetic properties of BMCS NSs. We envision that this new strategy will open up exciting opportunities toward large-scalable production of such high-quality BMCS NSs, thereby greatly potentiating the prospective applications of nanomagnetic materials.

6.
Nanoscale ; 11(16): 7648-7655, 2019 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-30720812

RESUMO

The first stage of biofilm-associated infections is commonly caused by initial adhesion of bacteria to intravascular tubes, catheters and other medical devices. The overuse of antibiotics to treat these infections has led to the spread of antibiotic resistance, which has made infections difficult to eradicate. It is crucial to develop advanced strategies to inhibit biofilm formation, avoiding the emergence of antibiotic resistance. Previously, it has been reported that substrate stiffness plays an important role in the initial attachment of bacteria. However, the mechanism of how the stiffness modulates the initial adhesion of bacteria remains unclear. Here, we developed magnetic nanoprobe-based force-induced remnant magnetization spectroscopy (FIRMS) as a new platform to measure the adhesion force of bacteria. Through examining the initial adhesion force and the adhesive protein, fibronectin-binding protein (FnBP), of Staphylococcus aureus (S. aureus), we found that the increase of the substrate stiffness promoted the expression of FnBP, thus enhancing the initial adhesion force of bacteria. Following the formation of initial adhesion, the substrates with soft stiffness delayed the biofilm formation, whereas those with moderate stiffness showed preferential promotion of the biofilm formation. We expect this versatile platform to be beneficial to the study of adhesion behaviors of bacteria that sheds light on the design of new medical materials to treat microbial infections.


Assuntos
Aderência Bacteriana , Nanopartículas de Magnetita/química , Staphylococcus aureus/fisiologia , Adesinas Bacterianas/química , Adesinas Bacterianas/metabolismo , Biofilmes/crescimento & desenvolvimento , Microscopia de Força Atômica , Microscopia de Fluorescência
7.
Chemistry ; 25(12): 2978-2982, 2019 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-30600858

RESUMO

Multivalent interactions occur throughout biology, and have a number of characteristics that monovalent interactions do not. However, it remains challenging to directly measure the binding force of molecular multivalent interactions and identify the mechanism of interactions. In this study, the specific interaction between bivalent aptamer and thrombin has been measured directly and quantitatively by force-induced remnant magnetization spectroscopy to investigate the binding force and through-bond effects of the multivalent interactions. The measured differential binding forces enable through-bond effects in thrombin-aptamer complexes to be identified, where aptamer binding at exosite II produces visible effects on their binding at exosite I and vice versa. This method might be suitable for practical applications in the design of high-performance ligands.

8.
J Alzheimers Dis ; 61(4): 1611-1618, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29376851

RESUMO

BACKGROUND: Delayed Matching-to-Sample Task 48 (DMS48), a brief tool measuring visual recognition memory, is valid to identify the early stage of Alzheimer's disease (AD) in Caucasians. However, little data is available in Chinese. OBJECTIVE: To develop norms and optimal cutoff points for the DMS48 in Chinese elders. METHODS: A cross-sectional study was conducted in seven memory clinics from five cities across China. DMS48 was applied to 369 Chinese aged 50 or older (138 cognitively normal [CN], 112 mild cognitive impairment due to AD (MCI-A), and 119 mild AD dementia). The demographic factors which influence DMS48 scores were investigated and the norms were established considering those factors. Receiver operating characteristic (ROC) analysis was used to determine the optimal cutoff points. RESULTS: Age was shown to influence DMS48 scores (r = -0.36, p < 0.05), and we presented the age-stratified normative data for the DMS48. The optimal cutoff point is 42/43 for identifying cognitive impairment (MCI-A and AD dementia) against CN (sensitivity 97.80% and specificity 89.13%) and MCI-A against CN (sensitivity 86.60% and specificity 94.20%). A cutoff of 39/40 obtained good sensitivity (100.00%) and specificity (94.90%) in discriminating AD dementia from CN. The age-stratified optimal cutoff points for identifying MCI-A were 43/44 for individuals aged 50 to 59 years old, 42/43 for 60 to 69 years old, 41/42 for 70 to 79 years old, and 40/41 for 80 or older, respectively (sensitivity 84.80% and specificity 95.70%). CONCLUSION: This study proved that DMS48 is of good validation in screening MCI-A in elderly Chinese.

9.
Small ; 14(10)2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29271605

RESUMO

Macroporous particles that combine the property features of spherical structures and porous materials are expected to find use over micro- and macroscopic length scales from miniaturized systems such as cell imaging, drug and gene delivery to industrial applications. However, the capacity for de novo design of such materials is still limited. Here, a spontaneous process to fabricate monodisperse multifunctional macroporous particles (MMMPs) by high internal phase emulsion templating is reported. An interesting physical phenomenon involving self-emulsification and synergistic effects between nanoparticles and amphiphilic diblock copolymers is observed in this process. These MMMPs, featured with tailor-made pore structures, pH responsiveness, and magnetic response, could be used as stimuli-responsive carriers for multiple functional molecules with a high loading and releasing efficiency. This new understanding regarding the underlying phenomena that control self-emulsification behavior and synergistic action in emulsion systems provides a unique outlook and a novel approach to the design of potentially multifunctional porous materials for controllable release and delivery processes.

10.
J Alzheimers Dis ; 61(2): 613-618, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29226866

RESUMO

Frontotemporal dementia with parkinsonism-linked to chromosome 17 (FTDP-17) is a rare autosomal dominant neurodegenerative disorder. Most patients with FTDP-17 carry the mutation in the microtubule-associated protein tau (MAPT) gene. Striatum is predominantly and early affected in FTDP-17. Five family members (two symptomatic patients and three presymptomatic mutation carriers) from a Chinese pedigree of FTDP-17 with N279K mutation in MAPT were enrolled. Parkinsonism was the initial symptom for symptomatic patients. 2b-carbomethoxy-3b-(4-trimethylstannylphenyl) tropane (11C-CFT) uptake was obviously affected in the putamen of two presymptomatic mutation carriers. Presymptomatic case 3, whose 11C-CFT uptake in the right putamen was normal at baseline, was still free of parkinsonism during follow-up. In conclusion, 11C-CFT-positron emission tomography could be a potential biomarker for the presymptomatic stage of FTDP-17 to predict the disease onset.

11.
ACS Cent Sci ; 3(8): 860-867, 2017 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-28852700

RESUMO

To understand the hierarchical self-organization behaviors of soft materials as well as their dependence on molecular geometry, a series of AB n dendron-like molecules based on polyhedral oligomeric silsesquioxane (POSS) nanoparticles were designed and synthesized. The apex of these molecules is a hydrophilic POSS cage with 14 hydroxyl groups (denoted DPOSS). At its periphery, there are different numbers (n = 1-8) of hydrophobic POSS cages with seven isobutyl groups (denoted BPOSS), connected to the apical DPOSS via flexible dendron type linker(s). By varying the BPOSS number from one to seven, a supramolecular lattice formation sequence ranging from lamella (DPOSS-BPOSS), double gyroid (space group of Ia3̅d, DPOSS-BPOSS2), hexagonal cylinder (plane group of P6mm, DPOSS-BPOSS3), Frank-Kasper A15 (space group of Pm3̅n, DPOSS-BPOSS4, DPOSS-BPOSS5, and DPOSS-BPOSS6), to Frank-Kasper sigma (space group of P42/mnm, DPOSS-BPOSS7) phases can be observed. The nanostructure formations in this series of AB n dendron-like molecules are mainly directed by the molecular geometric shapes. Furthermore, within each spherical motif, the spherical core consists hydrophilic DPOSS cages with flexible linkages, while the hydrophobic BPOSS cages form the relative rigid shell, and contact with neighbors to provide decreased interfaces among the spherical motifs for constructing final polyhedral motifs in these Frank-Kasper lattices. This study provides the design principle of molecules with specific geometric shapes and functional groups to achieve anticipated structures and macroscopic properties.

12.
Adv Mater ; 29(19)2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28295720

RESUMO

Block copolymers (BCPs) have the capacity to self-assemble into a myriad of well-defined aggregate structures, offering great promise for the construction of drug delivery, photolithographic templates, and complex nanoscale assemblies. A uniqueness of these materials is their propensity to become kinetically frozen in non-equilibrium states, implying that the process of self-assembly can be utilized to remodel the resulting structures. Here, a new semiconfined system for processing the BCP self-assembly is constructed, in which an unusual dual-phase separation occurs, including nonsolvent-induced microphase separation and osmotically driven macrophase separation, ultimately yielding heterogeneous BCP membranes. These membranes with cellular dimensions show unique anisotropy that can be used for cell encoding and patterning, which are highly relevant to biology and medicine. This processing method not only provides new levels of tailorability to the structures and encapsulated contents of BCP assemblies, but can also be generalized to other block polymers, particularly those with attractive electronic and/or optical properties.

13.
J Neurol Sci ; 372: 379-386, 2017 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-27838006

RESUMO

The missense mutation V717I in amyloid precursor protein (APP) gene has been reported in many early-onset familial Alzheimer's disease (EOFAD) families. However, no detailed clinical picture regarding this mutation has ever been described for Chinese EOFAD. We investigate the age at onset (AAO), initial clinical features and non-cognitive neurological symptoms in 34 affected subjects from five Han Chinese EOFAD families with the APPV717I mutation to characterize the clinical phenotype. The AAO was 54.7±4.9years (n=34), with the APOE ɛ4 allele correlating with a decreased AAO. Prominent early affective symptoms, executive dysfunction and disorientation at onset were exhibited in 26 (76.5%), 18 (52.9%) and 16 (47%) cases, respectively. Spastic paraparesis and cerebellar ataxia occurred frequently in 13 (38.2%) and 12 (35.3%) cases, respectively, during the late stages of disease. The specific clinical phenotype of the APPV717I mutation for Chinese families is characterized by prominent early affective symptoms, executive dysfunction and disorientation as well as frequent late spastic paraparesis and cerebellar ataxia as compared to Western reports. We conclude that ethnic differences, environment or additional unknown factors may challenge the homogeneity of EOFAD with identical APP mutations.


Assuntos
Doença de Alzheimer/genética , Precursor de Proteína beta-Amiloide/genética , Saúde da Família , Mutação/genética , Idade de Início , Idoso , Doença de Alzheimer/diagnóstico por imagem , Análise de Variância , Apolipoproteína E4/genética , Grupo com Ancestrais do Continente Asiático/etnologia , Grupo com Ancestrais do Continente Asiático/genética , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/genética , Análise Mutacional de DNA , Feminino , Humanos , Isoleucina/genética , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Transtornos do Humor/etiologia , Transtornos do Humor/genética , Testes Neuropsicológicos , Valina/genética
14.
Artigo em Inglês | MEDLINE | ID: mdl-26938543

RESUMO

Individuals afflicted with occupational formaldehyde (FA) exposure often suffer from abnormal behaviors such as aggression, depression, anxiety, sleep disorders, and in particular, cognitive impairments. Coincidentally, clinical patients with melatonin (MT) deficiency also complain of cognitive problems associated with the above mental disorders. Whether and how FA affects endogenous MT metabolism and induces cognitive decline need to be elucidated. To mimic occupational FA exposure environment, 16 healthy adult male mice were exposed to gaseous FA (3 mg/m³) for 7 consecutive days. Results showed that FA exposure impaired spatial memory associated with hippocampal neuronal death. Biochemical analysis revealed that FA exposure elicited an intensive oxidative stress by reducing systemic glutathione levels, in particular, decreasing brain MT concentrations. Inversely, intraperitoneal injection of MT markedly attenuated FA-induced hippocampal neuronal death, restored brain MT levels, and reversed memory decline. At tissue levels, injection of FA into the hippocampus distinctly reduced brain MT concentrations. Furthermore, at cellular and molecular levels, we found that FA directly inactivated MT in vitro and in vivo. These findings suggest that MT supplementation contributes to the rescue of cognitive decline, and may alleviate mental disorders in the occupational FA-exposed human populations.


Assuntos
Encéfalo/efeitos dos fármacos , Transtornos Cognitivos/etiologia , Cognição/efeitos dos fármacos , Formaldeído/efeitos adversos , Hipocampo/efeitos dos fármacos , Melatonina/fisiologia , Memória/efeitos dos fármacos , Hipersensibilidade Respiratória/fisiopatologia , Adulto , Animais , Humanos , Masculino , Camundongos , Exposição Ocupacional , Estresse Oxidativo/efeitos dos fármacos
15.
Adv Mater ; 28(16): 3131-7, 2016 04.
Artigo em Inglês | MEDLINE | ID: mdl-26923562

RESUMO

Amphiphilic Janus particles are successfully obtained via a powerful strategy combining diffusion-induced phase separation and magnetically driven dewetting. A large-area, amphiphilic monolayer is been formed via a self-assembly paradigm based on a synergy between the amphiphilicity, shape anisotropy, and external magnetic field. This functionality holds great promise for practical applications in intelligent coatings, anti-bioadhesion, and antifouling surfaces.


Assuntos
Difusão , Interações Hidrofóbicas e Hidrofílicas , Campos Magnéticos , Material Particulado/química , Material Particulado/síntese química , Molhabilidade , Anisotropia , Incrustação Biológica/prevenção & controle
16.
Zhonghua Yan Ke Za Zhi ; 50(6): 421-5, 2014 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-25241974

RESUMO

OBJECTIVE: To investigate the correlation of amaurosis fugax and carotid stenosis as well as posterior ocular blood vessel hemodynamic changes. METHODS: Case series studies. 32 patients (19 men and 13 women whose age were 50 to 80 years old and average age was 64.31 ± 8.15) who were diagnosed as amaurosis fugax with 32 eyes were enrolled from 2011.5-2012.12. During the same period 30 cases without posterior ocular ischemic diseases were collected as the control group. Their ophthalmic artery, central retinal artery and carotid artery were examinated by color Doppler ultrasound, to detect vascular peak systolic velocity, end diastolic velocity, resistance index, the degree of carotid stenosis, carotid artery plaque area and type. All data were analyzed by chi-square test and t-test. RESULTS: PSV (25.95 ± 2.45) cm/s, EDV (6.01 ± 0.87) cm/s of the ophthalmic artery in AmF group were lower compared with the control group [PSV:(27.53 ± 1.41) cm/s, EDV: (6.89 ± 0.56) cm/s]. The differences were statistically significant (t = 3.087, 0.712, P = 0.003, 0.048). There was no statistical difference of RI between AmF and the control group (t = 0.188, P = 0.852) . PSV (7.13 ± 0.96) cm/s, EDV (1.78 ± 0.26) cm/s of the central retinal artery in AmF group were lower compared with the control group[PSV:(8.23 ± 0.92) cm/s, EDV:(2.13 ± 0.29) cm/s]. The differences were statistically significant (t = 4.648, 4.976, P = 0.000, 0.000). There was no statistical difference of RI between AmF and the control group (t = 0.180, P = 0.855). Detection rate of carotid artery moderately and severe stenosis (59.4%) was significantly higher compared with the control group (6.7%) . The difference was statistically significant (χ(2) = 19.205, P = 0.000). CONCLUSIONS: The blood flow velocity of ophthalmic artery and central retinal artery in amaurosis fugax patients reduced significantly, while the resistance was normal. About 60% of the patients had carotid artery moderately and severe stenosis. There was significant correlation between amaurosis fugax and carotid artery stenosis.


Assuntos
Amaurose Fugaz/fisiopatologia , Artérias Carótidas/fisiopatologia , Estenose das Carótidas/diagnóstico por imagem , Artéria Oftálmica/fisiopatologia , Artéria Retiniana/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Amaurose Fugaz/diagnóstico por imagem , Velocidade do Fluxo Sanguíneo/fisiologia , Artérias Carótidas/diagnóstico por imagem , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Artéria Oftálmica/diagnóstico por imagem , Artéria Retiniana/diagnóstico por imagem , Ultrassonografia , Resistência Vascular/fisiologia
17.
J Phys Chem B ; 115(14): 3777-83, 2011 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-21417291

RESUMO

Stimuli response behaviors of cystamine-core dendrimer in the presence of several reducing agents including vitamin C, sodium bisulfite, and DL-Dithiothreitol are described. A competitive redox cleavage and supramolecular aggregate formation model is proposed based on PFG NMR and (1)H NMR titration experiments. Furthermore, reduction-responsive release of guest molecules from interior pockets of the cystamine-core dendrimer is confirmed by NOE studies. The results suggest that cystamine-core dendrimer is a versatile scaffold or precursor in the design of reduction-sensitive polymeric nanocapsules for biomedical purposes.


Assuntos
Cistamina/química , Dendrímeros/química , Ácido Ascórbico/química , Ácido Desoxicólico/química , Difusão , Ditiotreitol/química , Espectroscopia de Ressonância Magnética , Nanocápsulas/química , Oxirredução , Substâncias Redutoras/química , Sulfitos/química
18.
J Phys Chem B ; 114(34): 11017-26, 2010 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-20695473

RESUMO

The host-guest chemistry of dendrimer-biomacromolecule complexes is of great significance to both design and optimization of dendrimer-based drug delivery and host-guest systems. Here, we characterized the interactions between dendrimer and heparin by isothermal titration calorimetry (ITC), (1)H nuclear magnetic resonance ((1)H NMR), pulsed-field gradient (PFG) NMR, nuclear Overhauser effect spectroscopy (NOESY), and atomic force microscopy (AFM) studies. The calorimetric results suggest that miscellaneous aggregates are formed at different stages when heparin was titrated into a dendrimer solution: dendrimer-heparin "necklace" structures, followed by the formation of larger and more stable aggregates, and then macroscopic complexes which precipitate from the solution. The binding process is significantly influenced by dendrimer generation, surface functionality, and ion strength, indicating that the formation of dendrimer-heparin aggregates is predominantly driven by electrostatic interactions. The NMR results confirm the dendrimer-heparin binding models established by calorimetric measurement and present a new type of dendrimer-heparin aggregates at higher heparin/dendrimer molar ratios. Formulations containing generation 5 (G5) PAMAM dendrimers with a heparin/G5 molar ratio of 0.5-1.2 are proposed as effective ones for the treatment of thrombosis in noninvasive delivery routes such as nasal, pulmonary, transdermal, and oral routes. The combination of ITC and NMR in this study provides new insight into the interactions between globular and linear polymers and the delivery of macromolecular therapeutics such as heparin by dendrimers.


Assuntos
Dendrímeros/química , Heparina/química , Calorimetria , Portadores de Fármacos/química , Composição de Medicamentos , Heparina/administração & dosagem , Espectroscopia de Ressonância Magnética , Microscopia de Força Atômica , Concentração Osmolar , Eletricidade Estática
19.
J Phys Chem B ; 114(21): 7265-73, 2010 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-20462223

RESUMO

We studied the formation and growth of miscellaneous mixed micelles in dendrimer and surfactant mixtures. NMR techniques including (1)H NMR titration, diffusion (PGSE and DOSY) measurement, and NOE analysis were used to investigate the shape, size, interaction mode, spatial localization, and molecular orientation of the formed dendrimer/surfactant aggregates at different stages. The results suggest the formation of the following supramolecular aggregates when an equal molar concentration of sodium dodecylsulfate (SDS) and sodium deoxycholate (SDC) were added into a generation 4 (G4) cationic dendrimer: (1) the encapsulation of the two surfactants in the interior pockets of dendrimer at extremely low surfactant concentrations; (2) the binding of SDS on the surface of G4 dendrimer above the saturated encapsulation concentration; (3) the formation of globular SDS micelles and SDC dimer in the aqueous solution above the CMC of each surfactant; (4) the accumulation of SDS molecules on the surface of dendrimer in a bilayer fashion at high surfactant concentrations; (5) the interactions of dendrimer with the globular SDS micelles; and (6) the encapsulation of SDC monomers or dimers in the globular SDS micelles. The competitive binding/encapsulation of the two surfactants at different stages was evaluated. The results provide a new insight into the interactions of dendrimers with mixed surfactant systems.

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