RESUMO
OBJECTIVE: To investigate the metabolism and brain tissue distribution of borneol-modified tanshinone IIA liposome (BO-TA-Lip) and its effect on NF-κB and ICAM-1 in cerebral ischemia reperfusion rats, thereby exploring the ameliorative mechanism of BO-TA-Lip on ischemic encephalopathy. METHODS: Particle size, entrapment efficiency, drug loading were measured to evaluate the preparation comprehensively. Metabolism and brain tissue distributions in vivo were measured by HPLC, and the pharmacokinetic parameters were calculated. In addition, 24 SD rats were randomly divided into sham, model, STS (sodium tanshinone IIA sulfonate, 30 mg/kg) and BO-TA-Lip groups (44 mg/kg). The middle cerebral artery occlusion (MCAO) rats were constructed with thread embolism method. Neurological deficits were scored using Zea Longa scoring standard. TTC and HE staining were used for the cerebral infarction and histopathological examination, respectively. The protein expression was examined by immunohistochemistry and Western blot. RESULTS: The average particle size, encapsulation efficiency and drug loading of BO-TA-Lip were (135.33 ± 7.25) nm, (85.95 ± 3.20)% and (4.06 ± 0.31)%, respectively. Both in the pharmacokinetic analysis of plasma and brain tissue, in BO-TA-Lip group, the peak concentration and the area under the curve increased, and the clearance rate decreased. The neurological deficit scores and infarct area of the BO-TA-Lip group were significantly lower than that of the model and STS groups. Besides, BO-TA-Lip reduced the protein expression of NF-κB, ICAM-1, IL-1ß, TNF-α and IL-6 in the brain tissue. CONCLUSION: BO-TA-Lip had higher bioavailability and better absorption in brain tissue, and could improve cerebral ischemia reperfusion injury, which might be related to the inhibitory effect of BO-TA-Lip in expression of NF-κB and ICAM-1.
Assuntos
Isquemia Encefálica , Traumatismo por Reperfusão , Abietanos , Animais , Isquemia Encefálica/tratamento farmacológico , Canfanos , Molécula 1 de Adesão Intercelular , Lipossomos , NF-kappa B , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/tratamento farmacológicoRESUMO
Solution radical homopolymerization of isobornyl acrylate (iBoA) under starved-feed higher temperature conditions unexpectedly leads to polymer product with low dispersity (<1.3) compared to the polymerization of butyl acrylate (BA) under identical conditions. Both backbiting and ß-scission reactions occur, as the poly(iBoA) product contains close to 100% terminal double bond (TDB) functionality. However, the addition of monomer to the midchain radicals formed by backbiting is sterically hindered, greatly reducing both short and long-chain branching. The poly(iBoA) macromonomer functions as an excellent addition-fragmentation agent, not only lowering dispersity but also providing a means to efficiently produce blocky acrylate copolymers through sequential monomer feeding in the starved-feed semibatch process.
Assuntos
Acrilatos , Polímeros , Canfanos , PolimerizaçãoRESUMO
Cell-based therapies are gaining prominence in treating a wide variety of diseases and using synthetic polymers to manipulate these cells provides an opportunity to impart function that could not be achieved using solely genetic means. Herein, we describe the utility of functional block copolymers synthesized by ring-opening metathesis polymerization (ROMP) that can insert directly into the cell membrane via the incorporation of long alkyl chains into a short polymer block leading to non-covalent, hydrophobic interactions with the lipid bilayer. Furthermore, we demonstrate that these polymers can be imbued with advanced functionalities. A photosensitizer was incorporated into these polymers to enable spatially controlled cell death by the localized generation of 1 O2 at the cell surface in response to red-light irradiation. In a broader context, we believe our polymer insertion strategy could be used as a general methodology to impart functionality onto cell-surfaces.
Assuntos
Canfanos/química , Engenharia Celular , Polímeros/química , Células 3T3 , Animais , Humanos , Interações Hidrofóbicas e Hidrofílicas , Células Jurkat , Camundongos , Polimerização , Espectroscopia de Prótons por Ressonância MagnéticaRESUMO
BACKGROUND The purpose of the present research is to analyze the effect of polyphenols and flavonoids substrat (PFS) from plants Calendula officinalis, Salvia fruticosa, Achillea millefolium, and propolis as immunomodulatory in the production of interleukin (IL)-1ß and IL-10 in peripheral blood leukocytes medium (PBLM) in patients who were diagnosed with mucositis of peri-implant tissue compared to patients with healthy implant tissue. It was hypothesized that IL-1ß and IL-10 contribute to the inflammation processes noticed in the diseases of peri-implant tissues. MATERIAL AND METHODS Sixty non-smoking patients were included in this study: patients with healthy implants (HP group) and patients with peri-implant mucositis (MP group). Peri-mucositis was diagnosed by radiologic and clinical examination. The PBLM from MP were treated with PFS at various concentrations. The levels of IL-10 and IL-1ß excreted by the PBLM stimulated and unstimulated with viable Porphyromonas gingivalis test-tube were committed by the enzyme amplified immunoassay sensitivity method. RESULTS Unstimulated and stimulated PBLM and treatment with 5.0 mg/mL or 10.0 mg/mL of PFS in the MP group produced significantly higher levels IL-10 (P<0.001) that analogous mediums of the HP group. The levels of IL-1ß decreased more considerably in the stimulated PBLM of the MP group than in those of HP group (P<0.001) after the treatment with PFS at only 10.0 mg/mL concentration. CONCLUSIONS Theses results suggest that the solution of PFS might offer a new potential for the development of a new therapeutic path to prevent and treat peri-implant mucositis.
Assuntos
Interleucina-10/biossíntese , Interleucina-1beta/biossíntese , Leucócitos/imunologia , Estomatite/tratamento farmacológico , Achillea/química , Idoso , Calendula/química , Canfanos , Implantes Dentários , Índice de Placa Dentária , Medicamentos de Ervas Chinesas/farmacologia , Feminino , Flavonoides/farmacologia , Humanos , Interleucina-10/imunologia , Interleucina-1beta/imunologia , Leucócitos/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Mucosite/tratamento farmacológico , Panax notoginseng , Peri-Implantite/metabolismo , Índice Periodontal , Extratos Vegetais/farmacologia , Polifenóis/farmacologia , Porphyromonas gingivalis/efeitos dos fármacos , Salvia miltiorrhiza , Estomatite/sangue , Estomatite/imunologiaRESUMO
The influence of esters based on gamma-aminobutyric acid (GABA) and mono-/bicyclic terpenoids on membrane structure was investigated. The mechanism of action for terpenoid esters on phospholipids of artificial membranes and lipids isolated from the rat stratum corneum was studied by fluorescence and FT-IR spectroscopy. We report here, that inclusion of monocyclic terpenoid esters in phospholipid liposomes leads to growth of excimer to monomer ratio (IE/IM) indicating a decrease of membrane microviscosity. Another mechanism of influence on biomembranes was proposed for ester of bicyclic borneol - in this case a high ratio of vibronic peak intensities (I1/I3) was revealed. The addition of terpenoid esters appears in the FT-IR spectra as intensity reduction of absorption bands associated with C = O, P = O and P-O-С groups of lecithin phospholipids. Similar results were obtained after esters addition to lipids isolated from stratum corneum indicating a decrease of hydrogen bonds number between polar groups of lipids. Thus, the influence of terpenoid esters on molecular organization of the lipid matrix substantiates the feasibility of their use after transdermal delivery in vivo.
Assuntos
Ésteres/química , Lipossomos/química , Membranas Artificiais , Fosfolipídeos/química , Terpenos/química , Ácido gama-Aminobutírico/química , Administração Cutânea , Animais , Canfanos/química , Ligação de Hidrogênio , Lecitinas/química , Masculino , Fluidez de Membrana , Pirenos/química , Ratos Wistar , ViscosidadeRESUMO
Ginkgolides (GG), containing ginkgolide A (GA), ginkgolide B (GB) and ginkgolide C (GC), are mainly prescribed for ischemic stroke and cerebral infarction. However, the ginkgolides can hardly pass the blood-brain barrier (BBB) into the brain. The purpose of this study was to prepare borneol-modified ginkgolides liposomes (GGB-LPs) to study whether borneol could enhance the transport of ginkgolides across the BBB. The preparation conditions of GGB-LPs were optimized by a response surface-central composite design. Also, pharmacokinetics and biodistribution studies of GGB-LPs were conducted using UPLC-MS. The optimal preparation conditions for GGB-LP were as follows: ratio of lipid to drug (w/w) was 9:1, ratio of phospholipid to cholesterol (w/w) was 7:1, and hydrate volume was 17.5 mL. Under these conditions, the GGB-LP yield was 89.73 ± 3.45%. With GGB-LPs, borneol significantly promoted the transport of ginkgolide across the BBB. The pharmacokinetic parameters of GGB-LP were significantly improved too, with Tmax of 15 min and a high drug concentration of 3.39 µg/g in brain. Additionally, the drug targeting index and relative uptake rate of GGB-LP was increased. Borneol-modified ginkgolide liposomes can thus potentially be used to improve the BBB permeability of gingkolide formulations.
Assuntos
Barreira Hematoencefálica/metabolismo , Canfanos , Células Endoteliais/metabolismo , Ginkgolídeos , Animais , Barreira Hematoencefálica/patologia , Canfanos/química , Canfanos/farmacocinética , Canfanos/farmacologia , Linhagem Celular Transformada , Células Endoteliais/patologia , Ginkgolídeos/química , Ginkgolídeos/farmacocinética , Ginkgolídeos/farmacologia , Lipossomos , Camundongos , PermeabilidadeRESUMO
Disgust has been proposed to have evolved as a means to rid the body and mouth of noxious substances and toxins, as well as to motivate and facilitate avoidance of contact with disease-causing organisms and infectious materials. Nonemetic species, such as the rat, show distinctive facial expressions, including the gaping reaction, indicative of nausea-based disgust. These conditioned disgust responses can be used to model anticipatory nausea in humans, which is a learned response observed following chemotherapy treatment. As social factors play a role in the modulation and expression of conditioned disgust responses in rats, and the nonapeptide, oxytocin (OT), is involved in the modulation of social behavior, the present study examined the effects of an OT antagonist, L-368 899, on the development and expression of socially mediated conditioned disgust in male rats. When administered 10 min before testing in a distinct context (different from the original conditioning context), L-368 899 (5 mg/kg) significantly decreased gaping behavior in rats that were conditioned with a social partner. LiCl-treated rats administered L-368 899 before testing also showed decreased social initiations toward their social partner. These findings suggest that OT may play a role in the modulation and expression of socially mediated conditioned disgust in rats.
Assuntos
Canfanos/farmacologia , Condicionamento Psicológico/fisiologia , Ocitocina/metabolismo , Piperazinas/farmacologia , Vômito Precoce/psicologia , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Comportamento Animal/efeitos dos fármacos , Comportamento Animal/fisiologia , Expressão Facial , Cloreto de Lítio/toxicidade , Masculino , Náusea/psicologia , Ratos , Ratos Long-Evans , Comportamento SocialRESUMO
Xingnaojing microemulsion (XNJ-M) administered intranasally is used for stroke treatment. In order to decrease the XNJ-M-induced mucosal irritation, XNJ-M modified by mPEG2000-PLA (XNJ-MM) were prepared in a previous work. The present work aimed to assess the impact of mPEG2000-PLA on pharmacokinetic features and brain-targeting ability of XNJ-M. The bioavailability and brain-target effects of borneol and geniposide in XNJ-M and XNJ-MM were compared in mice after intravenous (i.v.) and intranasal (i.n.) administrations. Gas chromatography, high-performance liquid chromatography, and ultra-performance liquid chromatography/tandem mass spectrometry methods were developed for the quantification of borneol and geniposide. Blood and brain samples were collected from mice at different time points after i.v. and i.n. treatments with borneol at 8.0 mg/kg, geniposide at 4.12 mg/kg. In addition, near-infrared fluorescence dye, 1,1'-dioctadecyl-3,3,3',3'-tetramethyl indotricarbocyanine iodide was loaded into microemulsions to evaluate the brain-targeting ability of XNJ-M and XNJ-MM by near-infrared fluorescence imaging in vivo and ex vivo. For XNJ-M and XNJ-MM, the relative brain targeted coefficients (Re) were 134.59% and 198.09% (borneol), 89.70% and 188.33% (geniposide), respectively. Besides, significant near-infrared fluorescent signal was detected in the brain after i.n. administration of microemulsions, compared with that of groups for i.v. administration. These findings indicated that mPEG2000-PLA modified microemulsion improved drug entry into blood and brain compared with normal microemulsion: the introduction of mPEG2000-PLA in microemulsion resulted in brain-targeting enhancement of both fat-soluble and water-soluble drugs. These findings provide a basis for the significance of mPEG2000-PLA addition in microemulsion, defining its effects on the drugs in microemulsion.
Assuntos
Encéfalo/efeitos dos fármacos , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/farmacocinética , Emulsões/administração & dosagem , Cavidade Nasal/metabolismo , Poliésteres/química , Polietilenoglicóis/química , Administração Intranasal , Animais , Disponibilidade Biológica , Canfanos/química , Sistemas de Liberação de Medicamentos , Medicamentos de Ervas Chinesas/química , Emulsões/química , Emulsões/farmacocinética , Iridoides/química , Masculino , Camundongos , Camundongos Endogâmicos ICR , Acidente Vascular Cerebral/tratamento farmacológicoRESUMO
BACKGROUND: To determine the effect of Salvia przewalskii extract (SPE) from total phenolic acids on puromycin aminonucleoside (PAN)-induced rat podocyte injury. METHODS: The rats were divided into groups that were treated with either PAN only or PAN followed by tacrolimus or SPE. We evaluated the effects of SPE on podocyte injury 5, 10, 15 and 21 days following treatment. RESULTS: (1) Proteinuria was observed starting on day 5 in all groups. The peak levels of proteinuria differed among the groups with tacrolimus and high-dose SPE, which significantly decreased proteinuria relative to the PAN and low- and medium-dose SPE groups. The proteinuria in each group decreased by day 15 and returned to a normal level by day 21. (2) H&E and PAS staining revealed no abnormality in glomerular morphology. With electron microscopy, we observed foot process effacement in the rats of all groups starting on day 5, but rats in the tacrolimus and high-dose SPE groups exhibited a lower degree. (3) IHC staining of nephrin and podocin revealed unaffected expression and better linear distributions in the high-dose SPE and tacrolimus groups. Western blot analysis confirmed that SPE could improve the expression of proteins. (4) The mRNA levels of nephrin and podocin in the tacrolimus and high-dose SPE groups were significantly higher than that in the others. CONCLUSION: In our study, we first demonstrated the ability of SPE to reduce proteinuria, preserve the morphology and structure of podocytes and retain the levels of slit diaphragm proteins on PAN-induced rat podocytes injury.
Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Fitoterapia , Podócitos/efeitos dos fármacos , Proteinúria/prevenção & controle , Saliva , Animais , Canfanos , Avaliação Pré-Clínica de Medicamentos , Medicamentos de Ervas Chinesas/farmacologia , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Rim/metabolismo , Rim/patologia , Masculino , Proteínas de Membrana/metabolismo , Panax notoginseng , Proteinúria/induzido quimicamente , Proteinúria/metabolismo , Proteinúria/patologia , Puromicina , Ratos Sprague-Dawley , Salvia miltiorrhiza , TacrolimoRESUMO
Borneol, known as a "guide" drug in traditional Chinese medicine, is widely used as a natural penetration enhancer in modern clinical applications. Despite a large number of experimental studies on borneol's penetration enhancing effect, the molecular basis of its action on bio-membranes is still unclear. We carried out a series of coarse-grained molecular dynamics simulations with the borneol concentration ranging from 3.31% to 54.59% (v/v, lipid-free basis) to study the interactions of borneol with aDPPC(1,2-dipalmitoylsn-glycero-3-phosphatidylcholine) bilayer membrane, and the temperature effects were also considered. At concentrations below 21.89%, borneol's presence only caused DPPC bilayer thinning and an increase in fluidity; A rise in temperature could promote the diffusing progress of borneol. When the concentration was 21.89% or above, inverted micelle-like structures were formed within the bilayer interior, which led to increased bilayer thickness, and an optimum temperature was found for the interaction of borneol with the DPPC bilayer membrane. These findings revealed that the choice of optimal concentration and temperature is critical for a given application in which borneol is used as a penetration enhancer. Our results not only clarify some molecular basis for borneol's penetration enhancing effects, but also provide some guidance for the development and applications of new preparations containing borneol.
Assuntos
1,2-Dipalmitoilfosfatidilcolina/química , Canfanos/química , Membranas Artificiais , Simulação de Dinâmica Molecular , Difusão , Bicamadas Lipídicas/química , Porosidade , Reprodutibilidade dos Testes , Temperatura , Água/químicaRESUMO
Ultratrace 2-methylisoborneol (2-MIB, â¼ng/L) in source water is the main odorant in the algae-derived odor episodes, whose accurate on-site detection will have a promising application potential. Due to the chemical inertness of 2-MIB, sensitive and selective detection of 2-MIB remains much challenging. Herein, molecularly imprinted polymer cavities were polymerized on the heterostructure Ti3C2Tx@CuFc-metal-organic framework to selectively capture 2-MIB, where the heterostructure could catalyze the probe redox reaction of [Fe(CN)63-/4-] and amplify the corresponding current signals. The prepared electrochemical sensor showed higher sensitivity on 2-MIB detection than the reported ones. Excellent stability, reusability, and selectivity for 2-MIB detection were also verified. The linear range and limit of detection of our sensor for 2-MIB were optimized to 0.0001-100 µg/L and 30 pg/L, respectively, performing much better than the reported sensors. Comparable performance to gas chromatography-mass spectrometry was achieved when the sensor was applied to real water samples with or without 2-MIB standards. Overall, our research has made great progress in the application of an on-site sensor in 2-MIB detection and well advances the development of molecularly imprinted polymer-based electrochemical sensors.
Assuntos
Canfanos , Impressão Molecular , Água , Polímeros Molecularmente Impressos , Polímeros/química , Impressão Molecular/métodosRESUMO
Biofilm-associated infections remain a tremendous obstacle to the treatment of microbial infections globally. However, the poor penetrability to a dense extracellular polymeric substance matrix of traditional antibacterial agents limits their antibiofilm activity. Here, we show that nanoaggregates formed by self-assembly of amphiphilic borneol-guanidine-based cationic polymers (BGNx-n) possess strong antibacterial activity and can eliminate mature Staphylococcus aureus (S. aureus) biofilms. The introduction of the guanidine moiety improves the hydrophilicity and membrane penetrability of BGNx-n. The self-assembled nanoaggregates with highly localized positive charges are expected to enhance their interaction with negatively charged bacteria and biofilms. Furthermore, nanoaggregates dissociate on the surface of biofilms into smaller BGNx-n polymers, which enhances their ability to penetrate biofilms. BGNx-n nanoaggregates that exhibit superior antibacterial activity have the minimum inhibitory concentration (MIC) of 62.5 µg·mL-1 against S. aureus and eradicate mature biofilms at 4 × MIC with negligible hemolysis. Taken together, this size-variable self-assembly system offers a promising strategy for the development of effective antibiofilm agents.
Assuntos
Antibacterianos , Biofilmes , Canfanos , Guanidina , Testes de Sensibilidade Microbiana , Polímeros , Staphylococcus aureus , Biofilmes/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/síntese química , Guanidina/química , Guanidina/farmacologia , Canfanos/química , Canfanos/farmacologia , Polímeros/química , Polímeros/farmacologia , Tensoativos/química , Tensoativos/farmacologia , Humanos , Interações Hidrofóbicas e HidrofílicasRESUMO
Crocetin (CCT), a natural bioactive compound extracted and purified from the traditional Chinese medicinal herb saffron, has been shown to play a role in neurodegenerative diseases, particularly depression. However, due to challenges with solubility, targeting, and bioavailability, formulation development and clinical use of CCT are severely limited. In this study, we used the emulsification-reverse volatilization method to prepare CCT-loaded nanoliposomes (CN). We further developed a borneol (Bor) and lactoferrin (Lf) dual-modified CCT-loaded nanoliposome (BLCN) for brain-targeted delivery of CCT. The results of transmission electron microscope (TEM) and particle size analysis indicated that the size of BLCN (â¼140 nm) was suitable for transcellular transport across olfactory axons (â¼200 nm), potentially paving a direct path to the brain. Studies on lipid solubility, micropolarity, and hydrophobicity showed that BLCN had a relatively high Lf grafting rate (81.11 ± 1.33 %) and CCT entrapment efficiency (83.60 ± 1.04 %) compared to other liposomes, likely due to Bor improving the lipid solubility of Lf, and the combination promoting the orderly arrangement of liposome membrane molecules. Microplate reader and fluorescence microscopy analysis showed that BLCN efficiently promoted the endocytosis of fluorescent coumarin 6 into HT22 cells with a maximal fluorescence intensity of (13.48 ± 0.80 %), which was significantly higher than that of CCT (5.73 ± 1.17 %) and CN (12.13 ± 1.01 %). BLCN also exhibited sustained function, remaining effective for more than 12 h after reaching a peak at 1 h in cells, while CN showed a significant decrease after 4 h. The uptake mechanisms of BLCN in HT22 cells mainly involve energy-dependent, caveolae-mediated, and microtubule-mediated endocytosis, as well as micropinocytosis. Furthermore, BLCN displayed a significant neuroprotective effect on HT22 cells in glutamate-, corticosterone-, and H2O2-induced models. Tissue fluorescence image analysis of mice showed that BLCN exhibited substantial retention of fluorescent DiR in the brain after nasal administration for 12 h. These findings suggest that CCT has the potential for cellular uptake, neuroprotection, and targeted delivery to the brain following intranasal administration when encapsulated in Bor and Lf dual-modified nanoliposomes.
Assuntos
Encéfalo , Canfanos , Carotenoides , Lactoferrina , Lipossomos , Nanopartículas , Fármacos Neuroprotetores , Vitamina A , Animais , Vitamina A/química , Vitamina A/administração & dosagem , Vitamina A/análogos & derivados , Lipossomos/química , Carotenoides/química , Carotenoides/farmacologia , Camundongos , Encéfalo/metabolismo , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/administração & dosagem , Canfanos/química , Canfanos/farmacologia , Lactoferrina/química , Lactoferrina/farmacologia , Lactoferrina/administração & dosagem , Nanopartículas/química , Linhagem Celular , Tamanho da Partícula , Masculino , Estrutura Molecular , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Relação Estrutura-Atividade , Neuroproteção/efeitos dos fármacosRESUMO
OBJECTIVE: Angiogenesis depends on a complex interaction between cellular networks and mediators. The endocannabinoid system and its receptors have been shown to play a role in models of inflammation. Here, we investigated whether blockade of cannabinoid receptors may interfere with inflammatory angiogenesis. MATERIALS AND METHODS: Polyester-polyurethane sponges were implanted in C57Bl/6j mice. Animals received doses (3 and 10 mg/kg/daily, s.c.) of the cannabinoid receptor antagonists SR141716A (CB1) or SR144528 (CB2). Implants were collected at days 7 and 14 for cytokines, hemoglobin, myeloperoxidase, and N-acetylglucosaminidase measurements, as indices of inflammation, angiogenesis, neutrophil and macrophage accumulation, respectively. Histological and morphometric analysis were also performed. RESULTS: Cannabinoid receptors expression in implants was detected from day 4 after implantation. Treatment with CB1 or CB2 receptor antagonists reduced cellular influx into sponges at days 7 and 14 after implantation, although CB1 receptor antagonist were more effective at blocking leukocyte accumulation. There was a reduction in TNF-α, VEGF, CXCL1/KC, CCL2/JE, and CCL3/MIP-1α levels, with increase in CCL5/RANTES. Both treatments reduced neovascularization. Dual blockade of cannabinoid receptors resulted in maximum inhibition of inflammatory angiogenesis. CONCLUSIONS: Blockade of cannabinoid receptors reduced leukocyte accumulation, inflammation and neovascularization, suggesting an important role of endocannabinoids in sponge-induced inflammatory angiogenesis both via CB1 and CB2 receptors.
Assuntos
Corpos Estranhos/imunologia , Reação a Corpo Estranho/imunologia , Neovascularização Patológica/imunologia , Receptor CB1 de Canabinoide/imunologia , Receptor CB2 de Canabinoide/imunologia , Animais , Canfanos/farmacologia , Antagonistas de Receptores de Canabinoides/farmacologia , Citocinas/imunologia , Reação a Corpo Estranho/etiologia , Reação a Corpo Estranho/patologia , Leucócitos/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neovascularização Patológica/etiologia , Neovascularização Patológica/patologia , Piperidinas/farmacologia , Poliésteres , Poliuretanos , Pirazóis/farmacologia , Rimonabanto , Pele/imunologiaRESUMO
PURPOSE: To evaluate the effect of borneol on the brain targeting efficiency of aprotinin-conjugated poly (ethyleneglycol)-poly (L-lactic-co-glycolic acid) nanoparticles (Apr-NP) and the activity of huperzine A (Hup A) loaded nanoparticles to AD rats . METHOD: Apr-NP was prepared by emulsion and solvent evaporation method. The uptake of Apr-NP alone or combined with borneol by brain capillary endothelial cells (BCECs) was evaluated by incorporating coumarin-6 as a tracer. In vivo imaging and the distribution of Hup A in the brain were measured to investigate the brain delivery of Apr-NP in rats, with or without the oral administration of borneol. Morris water maze was used to evaluate the memory improvement effect of Hup A loaded nanoparticles (Apr-NP-Hup). RESULTS: Co-incubation with borneol could increase the uptake of nanoparticles by BCECs. Nanoparticles delivered into the rat brain were enhanced significantly by the co-administration of borneol. The pharmacological effects of Hup A loaded nanoparticles on improving the memory impairment of AD rats were greatly improved when combined with borneol. CONCLUSIONS: Borneol is a promising enhancer for brain-targeting delivery systems. When co-administered with aprotinin-modified nanoparticles, borneol could improve the brain targeting efficiency of nanoparticles significantly.
Assuntos
Doença de Alzheimer/tratamento farmacológico , Aprotinina/química , Encéfalo/metabolismo , Canfanos/química , Nanoconjugados/química , Poliésteres/química , Polietilenoglicóis/química , Alcaloides/administração & dosagem , Alcaloides/farmacocinética , Alcaloides/uso terapêutico , Doença de Alzheimer/metabolismo , Animais , Comportamento Animal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Células Endoteliais/metabolismo , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Camundongos Nus , Fármacos Neuroprotetores/administração & dosagem , Fármacos Neuroprotetores/farmacocinética , Fármacos Neuroprotetores/uso terapêutico , Ratos , Ratos Sprague-Dawley , Sesquiterpenos/administração & dosagem , Sesquiterpenos/farmacocinética , Sesquiterpenos/uso terapêutico , Distribuição TecidualRESUMO
The aims of this study were to prepare a thermosensitive composite hydrogel (TCH) by mixing 24% (w/v) poloxamer 407 (P407), 16% (w/v) poloxamer 188 (P188) and 0.1% (w/v) carbopol 940 (C940), and to determine the effect of natural borneol/ (2-hydroxypropyl)-ß-cyclodextrin (NB/HP-ß-CD) inclusion complex on the phase transition temperature, mechanical, rheological properties, and release behaviors of the TCH using the tube inversion method, a texture analyzer, a rheometer, and in vitro release , respectively. The results showed that as the concentration of NB/HP-ß-CD increased, the phase transition temperature of the TCH was increased from 37.26 to 38.34 °C and the mechanical properties of the TCH showed that the hardness, cohesiveness, strength, and adhesiveness were increased from 0.025 to 0.064 kg, 0.022 to 0.064 kg, 0.110 to 0.307 kg and 0.036 to 0.105 kg, respectively, but the rheological properties of the TCH showed that G', G'' and η were decreased from 7,760 to 157.50 Pa, 1,274 to 36.28 Pa and 1,252 to 25.37 Pas, respectively. The in vitro release showed that an increasing NB/HP-ß-CD concentration decreased the release rate of NB from the TCH, but the amount of NB released was more than 96% at 60 min, which showed the TCH had good release behavior.
Assuntos
Resinas Acrílicas/química , Poloxâmero/química , Adesividade , Canfanos/química , Elasticidade , Dureza , Hidrogéis , Reologia , Temperatura de Transição , Viscosidade , beta-Ciclodextrinas/químicaRESUMO
The aim of this study is to prepare self-microemulsifying drug delivery system (SMEDDS) of the mixture of paeonol (Pae) and borneol (Bor). Solubility test, ternary phase diagrams and simplex lattice method were employed to screen and optimize the formulation of the mixture of Pae and Bor-loaded SMEDDS. After formed into microemulsions, the particle diameter (PD) was determined and a TEM was employed to observe the microemulsions' morphology. The contents of Pae and Bor were determined by gas chromatography. As a result, while ethyl oleate (EO) as the oil phase, cremophor EL35 (EL35) as surfactant and Transcutol HP (HP) as cosurfactant, the range of the microemulsion on the ternary phase diagram was larger than other combinations. And at a ratio of 20:45:35, the microemulsions' PD was about 34 nm and the polydispersity index (PI) was about 0.2. There were 16% of Pae, 2% of Bor, 16% of EO, 37% of EL35 and 29% of HP in the prepared SMEDDS. The preparation process of the Pae and Bor-loaded SMEDDS based on Xingbi Fang is simple and feasible. This study provides a reference for the researches on the related traditional Chinese medicine and the related components.
Assuntos
Acetofenonas/administração & dosagem , Canfanos/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Medicamentos de Ervas Chinesas/administração & dosagem , Acetofenonas/toxicidade , Administração Intranasal , Animais , Bufonidae , Canfanos/toxicidade , Cílios/efeitos dos fármacos , Combinação de Medicamentos , Medicamentos de Ervas Chinesas/toxicidade , Emulsões , Etilenoglicóis/química , Feminino , Masculino , Mucosa Nasal/efeitos dos fármacos , Ácidos Oleicos/química , Tamanho da Partícula , Polietilenoglicóis/química , Solubilidade , Tensoativos/químicaRESUMO
Infection is a huge obstacle to wound healing. Thus, to enhance the healing of infected wounds, wound dressings that permit the dual delivery of antimicrobials and antioxidants are highly desirable. In this study, a series of gelatin-based nanofiber membranes with different curcumin contents were fabricated via solution electrospinning. The obtained membranes were characterized in terms of their morphologies, in addition to their physical, mechanical, and in vitro properties. The results showed that the membranes maintained an integrated morphology, excellent water absorption capability, satisfactory mechanical properties, and a high dissolution rate of curcumin. The addition of curcumin and borneol conferred the membranes the ability to inhibit Staphylococcus aureus and eliminate free radicals. Furthermore, cytocompatibility testing using the L929 cell line confirmed the excellent biocompatibility of the membranes. These gelatin-based nanofiber membranes loaded with curcumin and borneol can therefore be considered as promising materials for dressing wounds. Moreover, the use of biodegradable polymers and environmentally sustainable production techniques in this system render it suitable for the commercial manufacture of composite membranes.
Assuntos
Curcumina , Nanofibras , Antibacterianos/farmacologia , Bandagens , Canfanos , Curcumina/farmacologia , Gelatina , Polímeros , ÁguaRESUMO
Underwater facilities are often perplexed by severe and ubiquitous biofouling. The widely applied commercial antifouling materials still have several challenges in static applications. Herein, a polymer containing isoborneol and borane (PBABs), the borneol derivative structure and grafted pyridine-triphenylborane (PTPB) as antifouling groups were prepared by radical polymerization. PBABs showed high antibacterial rates for Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) of up to 95.1% and 81.1%, respectively, confirming superior antibacterial adhesion propertys. More importantly, PBABs effectively reduced the expression of mussel adhesion protein, indicating superior antifouling propertys, resulting from the synergistic effect of multiple antifouling functional groups on the material's surface. Therefore, the PBABs have been evaluated as noncytotoxic, low-cost, easily synthesized, and mass-produced, which demonstrates their great potential for actual marine applications.
Assuntos
Incrustação Biológica , Acrilatos , Antibacterianos/farmacologia , Aderência Bacteriana , Incrustação Biológica/prevenção & controle , Boro , Canfanos , Escherichia coli , Polímeros , Staphylococcus aureus , Propriedades de SuperfícieRESUMO
Preparation of antibacterial coating materials is considered an effective strategy to prevent medical device-related infections. In the present study, by combining 2-lactobionamidoethyl methacrylamide with a uniquely structured borneol compound, new copolymers poly(2-lactobionamidoethyl methacrylamide-co-glycidyl methacrylate-co-isobornyl acrylate) (poly(LAEMA-co-GMA-co-BA)) were synthesized by a simple free-radical polymerization. An amine containing silane layer was first prepared on the substrate surface by a silanization reaction. The glycopolymers were grafted onto the silane layer through covalent bonding to obtain glycosylated coatings. X-ray photoelectron spectroscopy (XPS) confirmed the successful preparation of the APTES-functionalized surface and polymer layers. The surface wettability was measured by the contact angle (CA). The coated surfaces were relatively flat and smooth as confirmed by Atomic Force Microscopy (AFM). Moreover, the prepared coatings showed good antibacterial adhesion properties toward both E. coli and S. aureus. Furthermore, no significant cytotoxicity to the MRC-5 cells (lung fibroblasts) in vitro was observed, indicating the good biocompatibility of the antibacterial coatings. This study provides an excellent strategy for designing an antibacterial surface containing glycopolymers and natural antibacterial compounds, and these coatings may be suitable for medical devices.