载紫杉醇的大黄酸偶联物纳米胶束的制备及初步评价

目的制备载紫杉醇的D-α-生育酚聚乙二醇1000琥珀酸酯(D-α-tocopheryl polyethylene glycol 1000 succinate,TPGS)修饰的羧甲基壳聚糖-大黄酸偶联物(PTX/TPGS-CR)纳米胶束,并对其进行初步评价。方法采用透析法,以载药量、包封率及粒径为指标,通过单因素考察优化PTX/TPGS-CR纳米胶束的制备工艺并进行验证。以溶血实验及血管刺激性实验初步考察PTX/TPGS-CR纳米胶束的安全性。四甲基偶氮唑盐微量酶反应比色法(MTT)法考察PTX/TPGS-CR纳米胶束对Hela细胞的毒性。通过激光扫描共聚焦显微镜定性和流式细胞仪定量考察Hela细胞对PTX/TPGS-CR纳米胶束的摄取情况。结果制备工艺优化后制得的PTX/TPGS-CR纳米胶束粒径为(197.3±4.4)nm,PDI为(0.131±0.021),电位为(-31.8±0.5)mV,载药量为(48.20±3.03)%,包封率为(87.26±4.91)%。溶血实验结果表明,其溶血率低于1.71%;血管静脉注射无明显刺激性。其对Hela细胞的杀伤作用具有浓度和时间依赖性,能被Hela细胞高效摄取。结论PTX/TPGS-CR纳米胶束载药量和包封率高,安全性好,其体外抗肿瘤活性稍优于Taxol?。     

Injectable in situ cross-linking hyaluronic acid/carboxymethyl cellulose based hydrogels for drug release

A series of injectable in situ cross-linking hyaluronic acid/carboxymethyl cellulose based hydrogels (HA/CMC) was prepared via disulfide bonds by the oxidation of dissolved oxygen. The results showed that HA/CMC hydrogels exhibited tunable gelling time, appropriate rheology properties, high swelling ratio, good stability, and sustained drug release ability. The gelling time of HA/CMC hydrogels ranged from 1.4 to 7.0 min, and the values of the storage modulus, complex shear modulus, dynamic viscosity, and yield stress of HA3/CMC3 hydrogel were about 5869 Pa, 5870 Pa, 587 Pa·s, and 1969 Pa, respectively. The degradation percentage of HA1/CMC1, HA2/CMC2, and HA3/CMC3 hydrogels were about 60, 49, and 41% after incubating 42 days, and the in vitro cumulative release percentage of BSA from HA1/CMC1, HA2/CMC2, and HA3/CMC3 drug-loaded hydrogels were about 99, 91, and 82% after 30 days. The series of injectable in situ cross-linking HA/CMC hydrogels exhibited good comprehensive performance, signifying that these hydrogels could be potentially used in the fields of short- and medium-term controlled drug release, cell encapsulation, regenerative medicine, and tissue engineering.     

Genotoxicity studies of glycidol fatty acid ester (glycidol linoleate) and glycidol

Glycidol fatty acid esters (GEs) are found in refined edible oils. Safety concerns have been alleged due to the possible release of glycidol (G), an animal carcinogen.     

A bilayer scaffold prepared from collagen and carboxymethyl cellulose for skin tissue engineering applications

Abstract

Treatment of chronic skin wound such as diabetic ulcers, burns, pressure wounds are challenging problems in the medical area. The aim of this study was to design a bilayer skin equivalent mimicking the natural one to be used as a tissue engineered skin graft for use in the treatments of problematic wounds, and also as a model to be used in research related to skin, such as determination of the efficacy of transdermal bioactive agents on skin cells and treatment of acute skin damages that require immediate response. In this study, the top two layers of the skin were mimicked by producing a multilayer construct combining two different porous polymeric scaffolds: as the dermis layer a sodium carboxymethyl cellulose (NaCMC) hydrogel on which fibroblasts were added, and as the epidermis layer collagen (Coll) or chondroitin sulfate-incorporated collagen (CollCS) on which keratinocytes were added. The bilayer construct was designed to allow cross-talk between the two cell populations in the subsequent layers and achieves paracrine signalling. It had interconnected porosity, high water content, appropriate stability and elastic moduli. Expression of vascular endothelial growth factor (VEGF), basic-fibroblast growth factor (bFGF) and Interleukin 8 (IL-8), and the production of collagen I, collagen III, laminin and transglutaminase supported the attachment and proliferation of cells on both layers of the construct. Attachment and proliferation of fibroblasts on NaCMC were lower compared to performance of keratinocyte on collagen where keratinocytes created a dense and a stratified layer similar to epidermis. The resulting constructs succesfully mimicked in vitro the natural skin tissue. They are promising as grafts for use in the treatment of deep wounds and also as models for the study of the efficacy of bioactive agents on the skin.     

Skin permeation and metabolism of di(2-ethylhexyl) phthalate (DEHP)

Phthalates are suspected to be endocrine disruptors. Di(2-ethylhexyl) phthalate (DEHP) is assumed to have low dermal absorption; however, previous in vitro skin permeation studies have shown large permeation differences. Our aims were to determine DEHP permeation parameters and assess extent of skin DEHP metabolism among workers highly exposed to these lipophilic, low volatile substances.     

软骨组织工程用羧甲基壳聚糖/氧化海藻酸钠 复合水凝胶的制备及体外评估

目的 优化羧甲基壳聚糖/氧化海藻酸钠（CMCS/OSA）复合水凝胶制备工艺,并应用于软骨组织工程。方法 制备氨基与醛基比例分别为2:1、1:1、1:2的CMCS/OSA复合水凝胶,并通过扫描电子显微镜观察、流变学检测、黏附拉力测试、溶胀率分析及细胞实验等方法评价复合水凝胶的微观形态、物理特性以及生物相容性,以制备满足软骨再生领域需求的水凝胶。结果 氨基与醛基比为1:1时,制备出的水凝胶具有良好的孔隙率、适宜的成胶时间、较强的黏附力及稳定的溶胀率等性质,对细胞有良好的生物相容性。结论 氨基与醛基比为1:1时制备出的CMCS/OSA复合水凝胶是软骨组织工程优异的支架材料。     

The relationship between accumulation of advanced glycation end products and expression of vascular endothelial growth factor in human diabetic retinas

Summary Both advanced glycation end products and vascular endothelial growth factor are believed to play a role in the pathogenesis of diabetic retinopathy. It is known that vascular endothelial growth factor causes retinal neovascularization and a breakdown of the blood-retinal barrier; how advanced glycation end products affect the retina, however, remains largely unclear. The substance N^e-(carboxymethyl)lysine is a major immunologic epitope, i. e. a dominant advanced glycation end products antigen. We generated an anti-N^e-(carboxymethyl)lysine antibody to investigate the relationship between the localization of advanced glycation end products and that of vascular endothelial growth factor in 27 human diabetic retinas by immunohistochemistry. Nine control retinas were also examined. In all 27 diabetic retinas, N^e-(carboxymethyl)lysine was located in the thickened vascular wall. In 19 of the 27 retinas, strand-shaped N^e-(carboxymethyl)lysine immunoreactivity was also observed around the vessels. In all 27 diabetic retinas, vascular endothelial growth factor revealed a distribution pattern similar to that of N^e-(carboxymethyl)lysine. Vascular endothelial growth factor was also located in the vascular wall and in the perivascular area. Neither N^e-(carboxymethyl)lysine nor vascular endothelial growth factor immunoreactivity was detected in the 9 control retinas. Vessels with positive immunoreactivity for N^e-(carboxymethyl)lysine and/or vascular endothelial growth factor were counted. A general association was noted between accumulation of N^e-(carboxymethyl)lysine and expression of vascular endothelial growth factor in the eyes with non-proliferative diabetic retinopathy (p < 0.01) and proliferative diabetic retinopathy (p < 0.05). [Diabetologia (1997) 40: 764–769] Received: 19 December 1996 and in revised form: 26 February 1997     

Rheological studies on the solubilization by the surfactant SDS of complexes between three acidic polysaccharides and an organic base chloride

Developments in the solubilization of complexes between the cationic polymer, poly(hexamethylenebiguanidinium chloride) (PHMBH⁺Cl^-) and acidic polysaccharides are reported. It was discovered that the anionic detergent sodium dodecyl sulphate (SDS) is an excellent solubilizer for these complexes, enabling several multi-component systems to be studied. SDS itself was shown to interact with PHMBH⁺CL^- to form a highly viscous solution. Maximum viscosity was obtained with a SDS : PHMBH⁺CL^- molar ratio of 15.6. SDS : PHMBH⁺Cl^- at this ratio served as a good solubilizer for the acidic polysaccharides (sodium alginate, sodium carboxymethyl cellulose, and xanthan), forming highly viscous fluids. The effect of temperature on the viscosity of these solutions was also examined.     

Alginate/quaternized carboxymethyl chitosan/clay nanocomposite microspheres: preparation and drug-controlled release behavior

Drug-delivery systems, using natural drug carriers, have become increasingly important because of their nontoxicity and biodegradability. In this study, firstly, quaternized carboxymethyl chitosan (QCMC) was intercalated into the interlayer of organic montmorillonite (OMMT) to obtain the QCMC/OMMT nanocomposites, their structure, morphology, and thermal stability were investigated. Next, crosslinked alginate/QCMC/OMMT (AQCOM) microsphere was obtained by crosslinking with CaCl₂, and the drug-controlled release behavior was evaluated with bovine serum albumin (BSA) as model drug. The results suggested that, carboxyl groups in alginate and QCMC crosslinked with Ca²⁺, quaternary ammonium groups in QCMC or OMMT electrostatically interacted with carboxyl groups in alginate, and there was stable three-dimensional network in AQCOM microsphere. The swelling ratio of AQCOM microspheres decreased with the increase of OMMT content, the lowest one was only about 45% compared to the microsphere without OMMT of 197%. Besides, the in vitro release results for BSA indicated that the AQCOM microsphere displayed more excellent encapsulation and controlled release capacities than the microsphere without OMMT. The in vitro active cutaneous anaphylaxis test was carried out on Guinea pigs, which revealed that AQCOM microsphere did not cause anaphylaxis. Therefore, QCMC/OMMT nanocomposites from natural materials are considerably suitable to apply as drug-controlled release carriers.