外科手术切除与瘤床间质内缓释化疗治疗复发性脑胶质瘤的效果研究

目的探讨外科手术切除与瘤床间质内缓释化疗对复发性脑胶质瘤的治疗效果。方法回顾性分析2014年6月至2016年6月于瑞金医院神经外科就诊的114例复发性脑胶质瘤患者,根据治疗方法不同,将患者分为两组,其中外科手术切除联合瘤床间质内缓释化疗组(A组) 51例,仅外科手术切除组(B组) 63例。手术后2～3周所有患者均接受放疗。统计分析两组之间的Karnofsky行为表现量表评分、肿瘤复发率和生存时间的差异。结果两组患者的术前一般资料比较差异无统计学意义,术后的Karnofsky行为表现量表评分[70(60～80) vs. 70(60～80)]差异也无统计学意义(P 0. 05)。A组患者的顺铂缓释聚合物在术后1个月完全生物降解。A组患者脑胶质瘤在术后6个月的复发率与B组相比(16/51=31. 4%vs. 25/63=39. 7%)差异无统计学意义(P 0. 05),但在12个月和24个月的复发率分别为45. 1%(23/51)、62. 7%(32/51),均显著低于B组患者12个月(37/63=58. 7%)和24个月(51/63=81. 0%)的复发率(P 0. 05)。A组患者总体生存时间的中位数(427. 5 d)明显长于B组患者(211. 0 d),差异有统计学意义(P=0. 001)。结论用顺铂缓释聚合物进行瘤床间质内化疗能降低复发性脑胶质瘤患者外科手术切除后的肿瘤复发率,并延长患者的生存时间。     

药物缓释载体材料在医药领域中的研究及应用

背景:药物缓释就是将小分子药物与高分子载体以物理或化学方法结合,在体内通过扩散、渗透等控制方式,将小分子药物以适当的浓度持续地释放出来,从而达到充分发挥药物功效的目的.目的:总结药物缓释载体材料特征及其在医药领域中的应用.方法:以"药物缓释、载体材料、生物降解、壳聚糖、聚乳酸、海藻酸钠"为中文关键词,以"Drug delivery,carrier material,biodegradable,chitosan,polylactic acid,sodium alginate"为英文关键词,采用计算机检索中国期刊全文数据库、PubMed数据库(1993-01/2010-11)相关文章.纳入高分子生物材料-药物缓释载体等相关的文章,排除重复研究或Meta分析类文章,共入选31篇文章进入结果分析.结果与结论:壳聚糖和聚乳酸是当前在药物缓释体系中应用较多的材料,它是将小分子药物与高分子载体以物理或化学方法结合,以适当的浓度持续地释放出来,从而达到充分发挥药物功效的目的,较单一生物材料具有显著优越性,具有更好的生物相容性和生物可降解性.目前很多研究仍处于实验阶段,还有一些问题有待于解决,如制剂质量方法不成熟,剂量较难控制,成本较高等.     

药物缓释载体材料在医药领域中的研究及应用

背景：药物缓释就是将小分子药物与高分子载体以物理或化学方法结合,在体内通过扩散、渗透等控制方式,将小分子药物以适当的浓度持续地释放出来,从而达到充分发挥药物功效的目的。目的：总结药物缓释载体材料特征及其在医药领域中的应用。方法：以＂药物缓释、载体材料、生物降解、壳聚糖、聚乳酸、海藻酸钠＂为中文关键词,以＂Drug delivery,carrier material,biodegradable,chitosan,polylactic acid,sodium alginate＂为英文关键词,采用计算机检索中国期刊全文数据库、PubMed数据库（1993-01/2010-11）相关文章。纳入高分子生物材料-药物缓释载体等相关的文章,排除重复研究或Meta分析类文章,共入选31篇文章进入结果分析。结果与结论：壳聚糖和聚乳酸是当前在药物缓释体系中应用较多的材料,它是将小分子药物与高分子载体以物理或化学方法结合,以适当的浓度持续地释放出来,从而达到充分发挥药物功效的目的,较单一生物材料具有显著优越性,具有更好的生物相容性和生物可降解性。目前很多研究仍处于实验阶段,还有一些问题有待于解决,如制剂质量方法不成熟,剂量较难控制,成本较高等。     

缓释靶向模式的胃癌药物

背景：目前胃癌药物缓释靶向的研究已经取得了显著成果,但仍存在一些问题。目的：总结近年胃癌药物缓释靶向模式的应用现状。方法：应用计算机检索维普数据库中与胃癌药物缓释靶向模式有关的文章,检索时限1998-01/2010-10。检索关键词：胃癌,缓释,靶向,gastric cancer,delayed release,target。最终纳入符合标准的文献31篇。结果与结论：目前对胃癌的淋巴靶向化疗研究较多,纳米炭在胃癌淋巴靶向化疗的应用已取得初步成果,应用前景令人鼓舞,有望成为胃癌淋巴靶向化疗的主要手段。但对如何选用合适的给药途径有待进一步研究,对如何联合用药、多途径用药和规范胃癌淋巴化疗的标准以及如何开展个体化治疗有待深入探索。胃癌药物的缓释靶向模式具有低毒高效性、功能性缓释特性以及良好的淋巴趋向性,可望有效抑制原发癌和淋巴结的转移率,缩小肿瘤,增加手术切除,降低术后复发和转移率,提高患者生存率和生活质量。     

缓释靶向模式的胃癌药物☆

背景:目前胃癌药物缓释靶向的研究已经取得了显著成果,但仍存在一些问题.目的:总结近年胃癌药物缓释靶向模式的应用现状.方法:应用计算机检索维普数据库中与胃癌药物缓释靶向模式有关的文章,检索时限1998-01/2010-10.检索关键词:胃癌,缓释,靶向,gastric cancer,delayed release,target.最终纳入符合标准的文献31篇.结果与结论:目前对胃癌的淋巴靶向化疗研究较多,纳米炭在胃癌淋巴靶向化疗的应用已取得初步成果,应用前景令人鼓舞,有望成为胃癌淋巴靶向化疗的主要手段.但对如何选用合适的给药途径有待进一步研究,对如何联合用药、多途径用药和规范胃癌淋巴化疗的标准以及如何开展个体化治疗有待深入探索.胃癌药物的缓释靶向模式具有低毒高效性、功能性缓释特性以及良好的淋巴趋向性,可望有效抑制原发癌和淋巴结的转移率,缩小肿瘤,增加手术切除,降低术后复发和转移率,提高患者生存率和生活质量.     

植入式药物缓释系统在骨缺损修复中的研究进展

植入式药物缓释系统的载体多源于植骨材料.现对目前国内外应用较为广泛的植骨载体材料从生物学特性、释药规律、承载的药物种类等方面在骨缺损修复中的研究及应用进行综述.     

脑胶质瘤术后敏感药物间质化疗联合增敏放疗的临床分析

目的:探讨脑胶质瘤术后敏感药物间质化疗联合增敏放疗的临床疗效.方法:恶性脑胶质瘤158例最大限度地全切或次全切,术中于瘤残腔内安置化疗囊,术后第2,4,6,8周分别注射一次经MTT法筛选出的敏感疗药物ACNU,BCNU,VM26,DDP,5-FU,MMC,ACR,ADM和BLM中的一种,生理盐水2～4 mL稀释后穿刺化疗囊,微泵调控注射6～8 h.同时行全脑增敏放疗,2 Gy/次,5次/周,总量55～60 Gy.以后成倍延长间质化疗时间间隔.结果:158例平均随访3年,无明显不良反应,其中显效(肿瘤完全消失)46例,有效(肿瘤部分消失)78例,无变化19例,恶化15例.平均生存时间66周,总有效率78.5%.结论:手术后敏感药物间质化疗联合增敏放疗治疗恶性脑胶质瘤安全显效.     

鼠胶质瘤模型在紫杉醇-聚乳酸纳米缓释纤维片抗胶质瘤中的应用

目的:紫杉醇由于水溶性低及全身毒性的问题而限制了其抗癌的临床应用,为克服这些缺陷,应用紫杉醇-聚乳酸纳米缓释膜片对鼠脑胶质瘤进行了局部缓释化疗,观察其对人脑胶质瘤细胞系C6抑瘤作用。方法:实验于2005-05/2006-03在中科院长春应用化学研究所高分子与物理国家重点实验室和吉林大学基础医学院实验室完成。Wistar雌性大鼠40只,在立体定向条件下选取大鼠脑右侧尾状核区为靶点,接种2×105个处于对数生长期的C6细胞,1周后经MRI检查后证实32只大鼠种植成功,将其随机分成2组各16只:①实验组:于接种C6脑胶质瘤细胞后第7天将紫杉醇-聚乳酸纳米缓释膜片(由中科院长春应用化学研究所徐秀玲博士惠赠)植入瘤细胞接种部位。②对照组:手术,但不植入膜片。观察两组一般情况及死亡时间;采用复查MRI检测及苏木精-伊红染色组织病理和免疫组织化学染色观察肿瘤生长情况。结果:①接种1周后MRI检查,脑内形成实体瘤,成瘤率为80%,无远隔转移;苏木精-伊红组织病理证实是胶质瘤,GFAP免疫组化染色阳性。②实验组平均生存期长于对照组[(56.5±18.7),(17.6±1.6)d,P<0.05];实验组肿瘤平均直径小于对照组(P<0.05)。结论:紫杉醇-聚乳酸纳米缓释膜片进行局部化疗可有效抑制脑胶质瘤细胞的生长。     

缓释药物的研究进展及临床应用

背景：各种制备缓释制剂的缓释材料很多,目前可用于生产的缓释材料有40多种,广泛应用于临床多种疾病的治疗。目的：对目前国内外几种重要的缓释药物载体材料及临床上常用的缓释药物进行总结。方法：应用计算机检索CNKI和PubMed数据库2000-01/2010-12关于缓释药物研究的文章,在标题和摘要中以＂缓释,药物,生物材料＂或＂sustained release,drug,biomaterials＂为检索词进行检索。选择文章内容与缓释药物密切相关的文章。排除Meta分析及重复性研究,最终纳入23篇文献进入结果分析。结果与结论：可生物降解的合成高分子材料受到普遍重视并得到广泛应用,壳聚糖以其良好的性能备受青睐,成为药物缓释的一种重要载体,生物降解高分子聚乳酸在药物缓释方面的应用,起到重要的治疗作用;纤维蛋白胶生物相容性高,能有效延缓药物释放,在临床很多领域广泛应用。     

缓释药物的研究进展及临床应用

背景:各种制备缓释制剂的缓释材料很多,目前可用于生产的缓释材料有40多种,广泛应用于临床多种疾病的治疗.目的:对目前国内外几种重要的缓释药物载体材料及临床上常用的缓释药物进行总结.方法:应用计算机检索CNKI和PubMed数据库2000-01/2010-12关于缓释药物研究的文章,在标题和摘要中以"缓释,药物,生物材料"或"sustained release,drug,biomaterials"为检索词进行检索.选择文章内容与缓释药物密切相关的文章.排除Meta分析及重复性研究,最终纳入23篇文献进入结果分析.结果与结论:可生物降解的合成高分子材料受到普遍重视并得到广泛应用,壳聚糖以其良好的性能备受青睐,成为药物缓释的一种重要载体,生物降解高分子聚乳酸在药物缓释方面的应用,起到重要的治疗作用;纤维蛋白胶生物相容性高,能有效延缓药物释放,在临床很多领域广泛应用.     

FTIR imaging for the characterization of controlled-release drug delivery applications.

The diffusion of nicotine in ethanol/water mixtures into an ethylene-vinyl acetate (EVA) copolymer membrane was studied by FTIR imaging. The spatial and temporal distribution of each component in the EVA membrane was demonstrated in the FTIR images. The concentration profiles extracted from these images showed that segregation occurs during diffusion. Nicotine diffuses into EVA ahead of the solvent for 0-60 wt% ethanol/water mixtures, but the segregation behavior changes as the ethanol in the solvent increases to 80 wt%; for the 80 wt% ethanol solvent, D(2)O leads the diffusion front, and for the 100% ethanol solvent, ethanol diffuses into EVA first. The initial swelling rates were calculated from the concentration profiles, and an exponential trend with increasing ethanol in the solvent was observed. The concentration profiles were also used to calculate average diffusion coefficients for the overall solutions and specifically for nicotine. The relative intensities of the aromatic ring stretching bands of nicotine in solution indicate that the solvation properties in pure ethanol and water are not equivalent; a pseudo-conjugation scheme between water and nicotine was proposed to account for this difference. Examination of the intensity of the carbonyl band of the EVA film revealed an interaction with the solvents by hydrogen bonding.     

Construction of a photothermal controlled-release microcapsule pesticide delivery system

This study aimed to achieve the controlled-release of bioactive ingredients in microcapsule pesticide delivery systems. A photothermal controlled-release microcapsule pesticide delivery system was constructed using chitosan and polydopamine (PDA) as the wall materials to encapsulate avermectin. All the prepared microcapsules were characterized by the methods of optical microscopy, scanning electron microscopy, transmission electron microscopy, and Fourier-transform infrared spectroscopy. The slow-release, UV-shielding, photothermal performance, and the nematicidal activity of the prepared microcapsules were also systematically investigated. The results indicated that the prepared microcapsules had excellent slow-release and UV-shielding performance when further encapsulated with the PDA layer relative to those of the non-PDA-encapsulated products. The photothermal sensitivity of the AVM@CS/CMA/PDA composite microcapsule under the irradiation of near-infrared light (NIR) was dramatically enhanced with the photothermal conversion efficiency (η) of 14.93%. Furthermore, the nematicidal activity of the AVM@CS/CMA/PDA composite microcapsule system was effectively improved on exposure to the irradiation of a light-emitting diode (LED) full-spectrum light. The strategies used in this study for developing the photothermal controlled-release pesticide delivery system might play an important role on improving utilization of pesticides.

A photothermal controlled-release microcapsule pesticide delivery system was constructed using chitosan and polydopamine as the wall materials to encapsulate avermectin, the utilization rate of avermectin was improved.     

Osmotic capsules: A universal oral, controlled-release drug delivery dosage form

An osmotic, oral, controlled-release capsule is described. This capsule provides drug delivery at fixed delivery rates (T_80% = 6 or 14 h) independent of drug properties (e.g., solubility) or drug loading, thereby allowing rapid development of investigational or commercial drugs, especially for proof-of-concept type clinical studies. The capsule body and cap are prepared with cellulose acetate and polyethylene glycol in acetone and water using high density polyethylene molds as templates and a conventional tablet pan coater. After the shells are removed from the molds manually, a laser hole is drilled in the end of the capsule body. The drug is introduced as a shaped tablet admixed with polyethylene oxide. A “push” tablet consisting of high molecular weight polyethylene oxide, microcrystalline cellulose, and sodium chloride is also inserted into the capsule body. The capsule halves lock together due to ridges, alleviating the need for a banding operation.     

A computational model for particle size influence on drug absorption during controlled-release colonic delivery.

The effect of particle size on the percent drug absorbed is computationally modeled for controlled-release dosage forms that deliver drug particles to the colon. The relative benefit of reducing particle size is mapped on a diagram of the drug's absorption rate constant (estimated from rat intestinal perfusion, CACO-2 or human intubation permeation rates) versus the drug's solubility. Some drugs fall into a limit of high percentage absorption even with large particles such that particle size reduction has little impact. Another group of drugs is solubility limited such that even with small particles, absorption is negligible. Between the two regions, only drugs with sufficiently high absorption rates are influenced by the drug dissolution rate and thereby the particle size. The size of this region is a function of dosing rate. Comparisons between calculated particle size effects on colon absorption as a function of colon volume suggest caution when using animal models to predict bioavailability from colonic drug delivery. This volume dependence also suggests that the particle size influence will vary as a function of the digestive cycle.     

Nanoparticle drug delivery system for intravenous delivery of topoisomerase inhibitors.

Camptothecin-based drugs, because of their poor solubility and labile lactone ring, pose challenges for drug delivery. The purpose of this research was to develop a nanoparticle delivery system for camptotheca alkaloids. After initial investigations SN-38 was selected as the candidate camptotheca alkaloid for further development. Nanoparticles comprising SN-38, phospholipids and polyethylene glycol were developed and studied in vitro and in vivo. The SN-38 formulations were stable in human serum albumin and high lactone concentrations were observed even after 3 h. In vivo studies in nude mice showed prolonged half-life of the active (lactone form) drug in whole blood and increased efficacy compared to Camptosar in a mouse xenograft tumor model.     

Ultrasound-mediated nail drug delivery system

A novel ultrasound-mediated drug delivery system has been developed for treatment of a nail fungal disorder (onychomycosis) by improving delivery to the nail bed using ultrasound to increase the permeability of the nail. The slip-in device consists of ultrasound transducers and drug delivery compartments above each toenail. The device is connected to a computer, where a software interface allows users to select their preferred course of treatment. In in vitro testing, canine nails were exposed to 3 energy levels (acoustic power of 1.2 W and exposure durations of 30, 60, and 120 seconds). A stereo -microscope was used to determine how much of a drug-mimicking compound was delivered through the nail layers by measuring brightness on the cross section of each nail tested at each condition, where brightness level decreases coincide with increases in permeability. Each of the 3 energy levels tested showed statistical significance when compared to the control (P < .05) with a permeability factor of 1.3 after 30 seconds of exposure, 1.3 after 60 seconds, and 1.5 after 120 seconds, where a permeability factor of 1 shows no increase in permeability. Current treatments for onychomycosis include systemic, topical, and surgical. Even when used all together, these treatments typically take a long time to result in nail healing, thus making this ultrasound-mediated device a promising alternative.     

Microporous membrane drug delivery system for indomethacin.

Indomethacin is a nonsteroidal anti-inflammatory drug (NSAID) used in the treatment of rheumatoid arthritis for more than a decade. The high incidence and severity of side effects, which are dose-related and associated with long-term administration, have limited its use. This has led to the search for new delivery systems which can overcome the side effects by controlling the drug release. In this study, Indomethacin Extended Release Formulation was developed by pelletization using the method of extrusion/spheronization. The drug containing pellets were further coated to achieve the required release profile as per USP. Coating systems developed on the principle of microporous membrane drug delivery using soluble salt gave the best results.     

Polymeric micellar pH-sensitive drug delivery system for doxorubicin.

A novel polymeric micellar pH-sensitive system for delivery of doxorubicin (DOX) is described. Polymeric micelles were prepared by self-assembly of amphiphilic diblock copolymers in aqueous solutions. The copolymers consist of a biocompatible hydrophilic poly(ethylene oxide) (PEO) block and a hydrophobic block containing covalently bound anthracycline antibiotic DOX. The starting block copolymers poly(ethylene oxide)-block-poly(allyl glycidyl ether) (PEO-PAGE) with a very narrow molecular weight distribution (Mw/Mn ca. 1.05) were prepared by anionic ring opening polymerization using sodium salt of poly(ethylene oxide) monomethyl ether as macroinitiator and allyl glycidyl ether as functional monomer. The copolymers were covalently modified via reactive double bonds by the addition of methyl sulfanylacetate. The resulting ester subsequently reacted with hydrazine hydrate yielding polymer hydrazide. The hydrazide was coupled with DOX yielding pH-sensitive hydrazone bonds between the drug and carrier. The resulting conjugate containing ca. 3 wt.% DOX forms micelles with Rh(a)=104 nm in phosphate-buffered saline. After incubation in buffers at 37 degrees C DOX was released faster at pH 5.0 (close to pH in endosomes; 43% DOX released within 24 h) than at pH 7.4 (pH of blood plasma; 16% DOX released within 24 h). Cleavage of hydrazone bonds between DOX and carrier continues even after plateau in the DOX release from micelles incubated in aqueous solutions is reached.     

Transdermal drug delivery system exposure outcomes

Transdermal drug delivery systems are increasingly popular, yet few data exist regarding medical outcomes after exposures. Using data collected through a Regional Poison Information System, this retrospective study identified 61 cases of transdermal drug delivery system exposures reported over a recent 5-year period. Exposure routes included dermal (48 patients), oral (10 patients), combined oral and dermal (one patient), parenteral use of gel residue (one patient), and combined oral and parenteral (one patient). Forty-four exposures (72%) were managed by home telephone consultation only. Eleven of 17 patients (18%) evaluated in health care facilities were admitted, including eight (13%) to intensive care units. Hospital admission correlated statistically with clonidine and fentanyl exposures, oral exposures, and drug abuse. Clonidine exposure also correlated statistically with intensive care admission. One fatality was recorded, and all other patients recovered uneventfully. Transdermal drug delivery system exposures are infrequently reported to our regional poison information center but are associated with a significant hospital use and admission rate.