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1.
Sandri G Poggi P Bonferoni MC Rossi S Ferrari F Caramella C 《The Journal of pharmacy and pharmacology》2006,58(10):1327-1336
The aim of the present work was to compare the penetration enhancement properties of chitosan hydrochloride (HCS) both as a polymeric solution and as a nanoparticulate system with that of trimethyl chitosan hydrochloride (TMC) on buccal mucosa. The hydrophilic high molecular weight fluorescein isothiocyanate dextran (FD4; 4400 Da) was used as a macromolecule model. The mechanism involved in the HCS (solution and nanoparticles) and TMC solution penetration enhancement was investigated on pig buccal mucosa, characterized by having stratified epithelium and lacking in tight junctions. The permeation/penetration of FD4 and the change in morphology and histology of the mucosa after contact with the polymers were assessed: the experiments were performed ex-vivo by applying the formulations on excised porcine buccal tissue. For the morphology and the histology studies, the epithelial cell layers from freshly excised pig buccal mucosa were analysed with light microscopy by means of routine histopathology analysis (haematoxylin and eosin staining and Toluidine blue staining) and immunohistochemistry reactions. The organization of desmosomal junctions was assessed by means of an immunochemical reaction on desmosomes and transmission electron microscopy. Confocal laser scanning microscopy (CLSM) was used to find evidence of the location of FD4 in the tissue. Furthermore, the increase of the FD4 apparent permeability coefficient was quantified by means of Franz diffusion cells using isolated buccal epithelium to demonstrate the penetration enhancement properties of the polymer systems. Morphological analysis, performed by light microscopy, transmission electron microscopy and CLSM, suggests a similar mechanism of penetration enhancement for both HCS and TMC solutions and for HCS nanoparticles. Such a mechanism probably involves a repackaging of the epithelial cells up to the basal membrane and a partial disarrangement of desmosomes. The cell viability and the nuclear integrity indicated on the semi-thin section stained with Toluidine blue and by CLSM analysis, respectively, suggest that HCS as a polymer solution and a nanoparticulate system, and TMC polymer solution, do not cause cell damage. Trimethyl chitosan and chitosan nanoparticulate systems were able to increase FD4 permeation across buccal epithelium to a greater extent than the chitosan solution. 相似文献
2.
This study sought to examine the effects of taking cholesterol-lowering medication on outcomes of depression among older depressed adults. 243 elderly depressed patients were treated using an antidepressant algorithm by a geriatric psychiatrist who administered the Montgomery-Asberg Depression Rating Scale (MADRS) at clinical visits up to six years. We defined remission and relapse as achieving MADRS scores less than 7 and greater than 15, respectively. There were no between-group differences on time to remission. Among 167 remitted patients with follow-up data, 61.4% on cholesterol-lowering medication, and 39.8% not on cholesterol medications experienced a relapse during the follow-up period (p<0.032), and remitted patients taking cholesterol medications relapsed more quickly than did others in adjusted analyses (hazard ratio=1.791, p<0.018). These results add to the literature linking cholesterol and mood, and they support the "vascular depression" hypothesis in geriatric depression. Future studies of depression outcomes in the elderly will need to include serial examination of cholesterol levels. 相似文献
3.
Paul Baldrick 《Regulatory toxicology and pharmacology : RTP》2010,56(3):290-299
Interest in use of the polysaccharide chitosan as a pharmaceutical excipient by different dose routes and for a number of applications is not new but it still does not appear to be present in any marketed drugs. Including a novel excipient in a new drug formulation requires a number of safety considerations. Review of the published literature showed that chitosan has low oral toxicity and local tolerance potential supporting use in non-parenteral formulations. Prior human oral exposure has occurred through use of chitosan dietary supplements and food additive, medical device and cosmetic applications. Although systemic exposure to parent chitosan may be limited (due to digestion in the gastrointestinal tract), any that is absorbed will likely undergo enzyme degradation to naturally occurring glucosamine, and N-acetylglucosamine, its copolymers, which are excreted or used in the amino sugar pool. Chitosan has local biological activity in the form of haemostatic action and, together with its ability to activate macrophages and cause cytokine stimulation (which has resulted in interest in medical device and wound healing applications), may result in a more careful assessment of its safety as a parenteral excipient. 相似文献
4.
Viviana García Mir Jyrki Hein?m?ki Osmo Antikainen Ofelia Bilbao Revoredo Antonio Iraizoz Colarte Olga Maria Nieto Jouko Yliruusi 《European journal of pharmaceutics and biopharmaceutics》2008,69(3):964-968
Deformation and compaction properties of native amino poly-saccharides chitin and chitosan were studied and compared with those obtained with established pharmaceutical direct compression excipients. An instrumented single-punch tablet machine was used for tablet compaction. The following compression parameters were evaluated: a ratio of crushing strength and compression pressure, plasticity and elasticity factor (PF and EF), tensile strength and R-value. Chitin and chitosan were found to have a marked tendency to plastic deformation, and both showed a good compression behaviour compared with the other direct compression excipients including microcrystalline cellulose. It is concluded that chitin and chitosan are potential co-excipients for direct compression applications. 相似文献
5.
Effect of molecular structure of chitosan on protein delivery properties of chitosan nanoparticles 总被引:1,自引:0,他引:1
Chitosan nanoparticles (CS NP) with various formations were produced based on ionic gelation process of tripolyphosphate (TPP) and chitosan. They were examined with diameter 20-200 nm and spherical shape using TEM. FTIR confirmed tripolyphosphoric groups of TPP linked with ammonium groups of chitosan in the nanoparticles. Factors affecting delivery properties of bovine serum albumin (BSA) as model protein have been tested, they included molecular weight (Mw) and deacetylation degree (DD) of chitosan, the concentration of chitosan and initial BSA, and the presence of polyethylene glycol (PEG) in encapsulation medium. Increasing Mws of chitosan from 10 to 210 kDa, BSA encapsulation efficiency was enhanced about two times, BSA total release in PBS (phosphate buffer saline) pH 7.4 in 8 days was reduced from 73.9 to 17.6%. Increasing DD from 75.5 to 92% promoted slightly the encapsulation efficiency and decelerated the release rate. The encapsulation efficiency was highly decreased by increase of initial BSA and chitosan concentration; higher loading capacity of BSA speeded the BSA release from the nanoparticles. Adding PEG hindered the BSA encapsulation and accelerated the release rate. 相似文献
6.
7.
Evaporation-freezing and rheological behaviour of chitosan dispersions at different temperatures and with different molecular weights using glycolic acid as anionic systems were studied. Chitosans of high, 2,000,000, medium, 750,000, and low, 70,000 molecular weight (hC, mC, and lC, respectively) were employed alone or as mixtures (hC/mC, hC/lC, and mC/lC 1:1, w/w). Different concentrations of glycols were added to these base dispersions (propylene glycol and glycerine) to investigate how the above physical properties change. The different rheological and evaporation-freezing behaviours of chitosan dispersions were related both to the molecular weight of chitosan and the vehicle composition of the dispersions. Particularly, the rheological study showed a pseudoplastic and shear thinning behaviour for all chitosan dispersions with flow index values n, tending to <1 at increasing molecular weights. Chitosans dispersions containing glycols showed lower apparent viscosity values than the base dispersions of the corresponding chitosans, but the water loss and the freezing point were lower especially for chitosan dispersions containing glycerine. This work presents a wide range of dispersion series from which to choose the most suitable to formulate pharmaceutical and cosmetic products. 相似文献
8.
目的:制备左旋聚乳酸-g-羟乙基壳聚糖(PLLA-g-HECS)复合支架,并进行性能测定。方法采用热致相分离法制备PLLA-g-HECS聚合物,再用压片机,将聚合物压模成形,测定复合支架的微观形貌、X射线衍射图谱分析、溶解实验及溶血试验。结果复合支架具有纳米微米共存的高孔隙直径的亚微观结构。X射线衍射图谱说明引入左旋聚乳酸链段后进一步减弱了HECS分子间和分子内较强的氢键作用。结论复合支架溶解实验显示复合物有较好的溶解性。溶血实验提示复合支架复合支架不会引起急性溶血反应,具有良好的生物相容性。 相似文献
9.
甘油广泛用于制药、食品和日化工业中,在药剂中常用作润滑剂、湿润剂、薄膜包衣增塑剂、防腐剂、溶剂、甜味剂等。但对于甘油的人体安全摄入范围尚无统一的标准。本文对国外甘油非临床安全性研究结果进行总结分析,包括一般毒理和特殊毒理特征,供新药非临床及临床研究评价参考。 相似文献
10.
The depolymerization of chitosan: effects on physicochemical and biological properties 总被引:5,自引:0,他引:5
Mao S Shuai X Unger F Simon M Bi D Kissel T 《International journal of pharmaceutics》2004,281(1-2):45-54
Chitosan has been extensively used as an absorption enhancer for macromolecules and as gene delivery vehicle. Both properties are molecular weight (MW) dependent. Here, we investigate factors affecting the oxidative depolymerization of chitosan and physicochemical properties of the resulting polymer fractions including their cytotoxicity. The molecular weight of the depolymerized chitosan was influenced by the initial concentration and the source of chitosan. At constant initial concentrations, the molecular weight decreased linearly with the chitosan/NaNO2 ratio and was a function of logarithm of the reaction time. Chitosan with larger molecular weight was more sensitive to depolymerization. No structural change was observed during the depolymerization process by infrared and proton nuclear magnetic resonance spectroscopy. In addition, thermal properties of chitosan fragments were studied by thermal gravimetric analysis and it was found that the decomposition temperature was molecular weight dependent. Furthermore, the solubility of different molecular weight chitosan was assayed as a function of pH and it increased with decreasing molecular weight. The cytotoxicity of chitosan was concentration dependent but almost molecular weight independent according to MTT assay using L929 cell line recommended by USP26. In summary, low molecular weight fractions of chitosan may potentially useful for the design of drug delivery systems due to the improved solubility properties. 相似文献
11.
The purpose of this study was to investigate the influence of different types of chitosan and of the preparation technique of the drug-polymer combination in improving the dissolution and permeation abilities of naproxen, a very poorly water-soluble anti-inflammatory drug. Drug-chitosan systems were prepared by simple physical mixing, kneading, cogrinding, or coevaporation using five types of chitosan (base and glutamate or hydrochloride salts, both at two different molecular weights). The products were tested for drug-dissolution behavior and for permeation properties through both Caco-2 cell monolayers and artificial lipophilic membranes. All combinations with chitosan base were significantly (p < .01) more effective in enhancing drug-dissolution rate than those with both its salts, probably in virtue of its higher amorphizing effect toward the drug, as observed in solid-state studies. A different rank order was found in permeation experiments in which chitosan glutamate was the most powerful partner in improving the drug-apparent permeability (p < .01), followed by the hydrochloride salt (p < .05), whereas no significant effect was obtained with chitosan base. Cogrinding was the most powerful technique in promoting both dissolution and permeation properties of the drug, thus pointing out the importance of the preparation method in obtaining efficacious drug-carrier systems. Finally, the good correspondence between permeation experiments with Caco-2 cells and those with the artificial lipophilic membrane indicated the suitability of this latter in preformulation studies for a rapid screening of the best carrier and the most efficient drug-carrier preparation method for improving the biopharmaceutical properties of drugs. 相似文献
12.
红曲霉降胆固醇有效成分的研究 总被引:11,自引:0,他引:11
红曲霉以其能产生大量天然红色素的特性而著称于世,此外还能产生多种有效的生理活性物质。日本学者对红曲降血脂,降血压等功能的发现,掀起了利用红曲开发保健食品的热潮。本文主要对红曲霉生产胆固醇合成途径中的限速酶抑制剂-MonacolinK类物质的研究、特性、药用价值和生产概况和进展等方面进行综述。 相似文献
13.
Ultrasonication of chitosan and chitosan nanoparticles 总被引:2,自引:0,他引:2
The objective of this study was to evaluate the effects of ultrasonication on chitosan molecules and nanoparticles. Molecular weight (M(v)) of chitosan HCl (M(v) 146 kDa and degree of deacetylation (DD) 96%) decreased linearly with increasing duration and amplitude of ultrasonication. DD and FTIR absorption were unaffected. X-ray diffraction (XRD) analysis suggested greater chain alignment in the ultrasonicated chitosan samples. Chitosan nanoparticles had mean diameter of 382 nm, polydispersity of 0.53 and zeta potential of 47 mV. Ultrasonication administered at increasing duration or amplitude decreased the mean diameter and polydispersity of the nanoparticles. Zeta potential and FTIR absorbance were unaffected, while XRD suggested a greater disarray of chain alignment in the nanoparticle matrix. Under the transmission electron microscope (TEM), freshly prepared nanoparticles were dense spherical structures which became fragmented after ultrasonication for 10 min at amplitude of 80. Untreated nanoparticle formulation turned turbid upon storage for 3 weeks at ambient conditions due to substantial swelling of the nanoparticles. Ultrasonicated nanoparticle formulation remained clear on storage. Although the particles had also swelled, they were no longer spherical, assuming instead an irregular shape with branching arms. In conclusion, high-intensity ultrasonication induced considerable damage on the chitosan nanoparticles which could affect their function as drug carriers. 相似文献
14.
Teruhiko Shimokawa Shoichiro Goto Tohru Ugawa Nami Hisamichi Shin Naganuma Yuichi Iizumi Noboru Sato Toichi Takenaka Tatsuhiko Kodama 《Drug development research》1996,38(2):86-92
YM-16638 was found in preclinical studies to be an orally active leukotriene antagonist. Because LY-171883, another leukotriene receptor antagonist with a similar structure to YM-16638, showed a triglyceride-lowering effect with a peroxisomal proliferative effect in monkeys fed a normal diet, we investigated whether YM-16638 also showed a serum triglyceride-lowering effect by examining serum and hepatic lipid levels in cynomolgus monkeys fed a normal diet supplemented with YM-16638 for 4 weeks at a daily dose of 3.75 mg (8.5 μmole), 30 mg (67.7 μmole) or 60 mg (135.4 μmole)/kg body weight. Monkeys given YM-16638 showed a dose-dependent decrease in serum total cholesterol. At 2 weeks of treatment, serum LDL- and HDL-cholesterol in the YM-16638 group showed marked decreases of 35% and 32%, respectively. However, serum triglyceride levels did not change. By contrast, hepatic cholesterol and cholesterol ester levels in this group were only slightly increased, without any effect on hepatic triglyceride level. In vitro investigation of the effect of YM-16638 on LDL-receptor activity and mRNA expression in the human hepatoma cell line HepG2 cells showed that YM-16638 increased LDL-receptor activity in a dose-dependent manner at 44 h of treatment. mRNA level in these cells was also increased 1.7-fold at 8 h of treatment. These results suggest that the decrease in serum cholesterol level in monkeys treated with YM-16638 may be due to an increase in hepatic LDL-receptor activity. Furthermore, they suggest that YM-16638 may represent a potent hypocholesterolemic drug without serious side effects. © 1996 Wiley-Liss, Inc. 相似文献
15.
Min-Ho Park Jong-Suep Baek Cho-A Lee Cheong-Weon Cho 《Journal of Pharmaceutical Investigation》2013,43(6):489-497
The aim of this study was to test stability of exenatide and compare physicochemical properties of PLGA nanoparticles. To make small, stable, uniform and highly encapsulated nanoparticles, various factors such as the components (polymer and stabilizer) and preparation condition (organic phase, temperature or sonication time) were considered. We tested the effect of organic phase, acid/base, ultrasonication time or temperature on exenatide to decide preparation condition of PLGA nanoparticles. And, PLGA nanoparticles were prepared by the double emulsion-solvent evaporation method and chitosan was selected as stabilizer. PLGA nanoparticles were characterized by yield, encapsulation efficiency, drug loading, particle size, zeta potential, polydispersity index and morphology. In this study, PLGA nanoparticles showed different physicochemical properties according to chitosan molecular weight. In case of particle size, PLGA nanoparticles using 0.5 g chitosan (4 kDa) showed biggest particle size (781.4 ± 24.1 nm) among PLGA nanoparticles prepared in this study and PLGA nanoparticles using 1 g chitosan (2 kDa) showed highest encapsulation efficiency (52.8 ± 1.7 %) among PLGA nanoparticles prepared in this study. And, all of PLGA nanoparticles using chitosan showed that polydispersity index was low and zeta-potential was increased. These results suggest that chitosan molecular weight affects physicochemical properties of PLGA nanoparticle. 相似文献
16.
《International journal of pharmaceutics》1998,166(1):75-88
The mucoadhesive properties of chitosan and chitosan microspheres were evaluated by studying the interaction between mucin and chitosan in aqueous solution by turbidimetric measurements and the measurement of mucin adsorbed on the microspheres. A strong interaction between chitosan microspheres and mucin was detected. Adsorption studies were carried out for the adsorption of mucin to chitosan microspheres with different crosslinking levels. The adsorption of type III mucin (1% sialic acid content), to chitosan microspheres followed Freundlich or Langmuir adsorption isotherms. When the contents of sialic acid was increased (i.e. type I-S mucin, 12% sialic acid content), the adsorption type followed more closely an electrostatic attraction type of isotherm. The heat of the adsorption was found to be 13–23 kJ/mol. A salt-bridge effect has been proposed for the interaction of the positively charged mucoadhesive chitosan microspheres with the negatively charged mucus glycoprotein. The extent of mucus adsorption was proportional to the absolute values of the positive zeta potential of chitosan microspheres and negative `zeta potential' of mucus glycoprotein. Factors leading to a reduction or a reversal of these absolute values (e.g. different crosslinking levels of chitosan microspheres, different types of mucin, different pH, or ionic strength of the medium used) led to a reduction in the amount adsorbed. The extent of this reduction depended upon the decreasing extent of the repective zeta potentials. Biological studies showed that chitosan microspheres were retained by a biological tissue; rat small intestine. 相似文献
17.
目的制备壳聚糖/聚乙烯醇(PVA)微球脲酶,探讨其最适温度、最适pH、热稳定性及其动力学。方法用微乳法制备壳聚糖/PVA微球,采用电子扫描电镜表征其形态;用吸附法获得壳聚糖/PVA微球脲酶;运用Berthlot测定其活力。结果壳聚糖/PVA微球脲酶酶活性保持率是原酶的91.93%,最适温度为47℃,最适pH6.5,热稳定性明显高于溶液脲酶;壳聚糖/PVA微球脲酶的动力学参数KM=11.8 mmo.lL-1,Vm ax=37.1μmo.lm in-.1mg-1。结论壳聚糖/PVA微球脲酶可制备成用于尿毒症患者的口服制剂。 相似文献
18.
目的以壳聚糖为载体材料,甲氨蝶呤为模型药物,制备鼻腔给药甲氨蝶呤壳聚糖微球。方法采用喷雾干燥法制备甲氨蝶呤壳聚糖微球;采用正交设计优化制备工艺,并对药物的包封率、收率、粒径以及释放行为进行考察。结果优化条件下所得微球粒径分布较为均匀,平均粒径为4.0~5.0μm,制成微球后药物可缓慢释放,符合鼻腔给药的要求。结论该方法适用于甲氨蝶呤壳聚糖微球的制备,壳聚糖是良好的鼻用制剂的载体材料,可用于制备脑部靶向鼻黏膜给药制剂。 相似文献
19.
Chitosan microspheres containing cis-platin were prepared using a w/o emulsion system. Variables important for microsphere properties were investigated: these include; chitosan, cis-platin and glutaraldehyde concentrations, the types of chitosan and oil, the cross-linking process and stirring rate. Chitosan and glutaraldehyde concentrations, the types of oil and chitosan have a significant effect on cis-platin entrapment in chitosan microspheres. In general, incorporation efficiency was high and ranged from 28-99%. The type and concentration of chitosan affected cis-platin release from microspheres. The type of oil was also important for release properties. Cis-platin release from microspheres is characterized by an initial burst effect. 相似文献
20.
Effect of formulation variables on cis-platin loaded chitosan microsphere properties 总被引:2,自引:0,他引:2
Chitosan microspheres containing cis-platin were prepared using a w/o emulsion system. Variables important for microsphere properties were investigated: these include; chitosan, cis-platin and glutaraldehyde concentrations, the types of chitosan and oil, the cross-linking process and stirring rate. Chitosan and glutaraldehyde concentrations, the types of oil and chitosan have a significant effect on cis-platin entrapment in chitosan microspheres. In general, incorporation efficiency was high and ranged from 28-99%. The type and concentration of chitosan affected cis-platin release from microspheres. The type of oil was also important for release properties. Cis-platin release from microspheres is characterized by an initial burst effect. 相似文献