基于炎症环境的口服结肠靶向给药系统研究进展

口服结肠靶向给药系统由于能改善结肠局部疾病的治疗效果和降低副作用而成为该领域的研究热点。口服给药系统设计方法的不断发展显著提高了药物在结肠部位的生物利用度,然而,要使药物在发病期能够发挥治疗效果,还须关注到结肠炎症时胃肠道出现生理条件变化的影响。纳米技术已经作为提高药物在结肠炎症病灶区摄取的新策略而应用于口服剂型设计中,本文主要介绍该纳米给药系统的设计方法和研究进展。     

靶向给药系统的研究进展

本文就近年来靶向给药系统作为药物载体的研究及其在临床治疗中的应用进行综述.     

Design and Development of Multiparticulate System for Targeted Drug Delivery to Colon

A multiparticulate system combining pH-sensitive property and specific biodegradability for colon-targeted delivery of metronidazole has been investigated. Cross-linked chitosan microspheres were prepared from an emulsion system using liquid paraffin as the external phase and solution of chitosan in acetic acid as the disperse phase. The multiparticulate system was prepared by coating cross-linked chitosan microspheres exploiting Eudragit® L-100 and S-100 as pH-sensitive polymers. Morphology and surface characteristics of the formulations were determined by scanning electron microscopy. Particle size of the chitosan microspheres was determined by optical microscopy while that of coated microspheres was determined by particle size analyzer. In vitro drug-release studies were performed in conditions simulating stomach-to-colon transit in presence and absence of rat caecal contents. The size of the microspheres was small and they were efficiently microencapsulated within Eudragit® microspheres, forming a multireservoir system. By coating the microspheres with Eudragit® pH-dependant release profiles were obtained. No release was observed at acidic pH; however, when it reached the pH where Eudragit® starts solublizing there was continuous release of drug from the formulation. Further, the release of drug was found to be higher in the presence of rat caecal contents, indicating the susceptibility of chitosan matrix to colonic enzymes released from rat caecal contents.     

Immunoconjugates: Applications in Targeted Drug Delivery for Cancer Therapy

Monoclonal antibodies can be produced against virtually any molecule, and unlike polyclonal anti-sera, they are highly specific. There has been great improvement in the monoclonal antibody production technique since its inception in 1975. The idea behind using monoclonals to direct cancer treatments is based on the fact that surfaces of tumor contain a wide variety of proteins, some of which are specific to the tumor type. Monoclonal antibodies that bind to such tumor-specific antigens could be used, either alone or as conjugates of drugs and toxins (immunoconjugates), to selectively seek out and destroy these tumor cells. Targeted drug delivery therapy of tumor using monoclonals or their conjugates has been reported by many investigators, and the early results are quite promising. However, many obstacles still have to be overcome before immunoconjugates become a valuable agent in the treatment of human diseases including cancer.     

多肽修饰脂质体靶向药物递送系统研究进展

目的介绍近年来多肽修饰脂质体靶向药物递送系统的研究进展。方法查阅和归纳总结近几年相关文献。结果阐述了精氨酸-甘氨酸-天冬氨酸（RGD）多肽、丙氨酸-脯氨酸-精氨酸-脯氨酸-甘氨酸（APRPG）多肽、细胞穿透肽（CPP）、血管活性肠肽（VIP）等修饰脂质体的研究进展。多肽修饰的包载药物的脂质体可以增加药物在体内的选择性,减少药物毒副作用,提高药物治疗指数。结论多肽分子是机体内一类重要的生物活性物质,将其作为导向物以配体-受体特异性结合的方式应用于靶向药物递送系统,具有良好的研究价值和应用前景。     

pH依赖—缓释型美沙拉秦结肠靶向小丸的制备与体外评价

以肠溶型和渗透型丙烯酸树脂为包衣材料制备ｐＨ依赖－缓释型美沙拉秦结肠靶向小丸,评价其体外释放特性。结果表明,包衣小丸在０．１ｍｏｌ／ＬＨＣｌ中２ｈ几乎不释放药物,在ｐＨ７．５缓冲液中具有较好的缓释作用。在模拟胃肠道各区段最高的和最低的ｐ变化的释放度试验中,均在对应小肠区段时开始缓慢释药。分别有４０％和７０％的药物进入结肠后释放。优于单独的肠溶或缓释制剂。     

Development and Evaluation of Microbial Degradation Dependent Compression Coated Secnidazole Tablets for Colonic Delivery

The present paper describes development of a polysaccharide based compression coated tablets of secnidazole for colon delivery. Core tablet containing secnidazole was compression coated with various proportions of guar gum, xanthan gum and chitosan, either alone or in combinations. Drug release studies were performed in simulated gastric fluid (SGF) for 2 h followed by simulated intestinal fluid (SIF, pH 7.4) up to 24 h. Secnidazole release from the prepared formulations was dependent on the type and concentration of polymer used in the formulation. Tablets coating containing either guar gum or xanthan gum showed ~30-40% drug release in 8 h. Further, in vitro dissolution studies of selected formulations performed in the dissolution media with rat caecal contents showed 54.48±0.24 - 60.42±0.16% of drug release. Formulations with single polymer in coating layer were unsuitable for targeting secnidazole release to colon region. Combination of chitosan with guar gum or xanthan gum exhibited control over secnidazole release.     

靶向释放智能纳米载体的研究进展

随着材料科学的进步,智能纳米载体在药物和基因靶向治疗方面取得了巨大的研究进展。智能纳米载体被化学信号、温度、pH等"触发器"激发后,能在特定部位响应性地释放药物或基因。该文从智能纳米载体的定义,不同类型靶向释放的智能纳米载体在药物和基因中的研究进展,靶向释放的智能纳米载体的不足及发展前景等方面进行综述。     

Activation of the Mononuclear Phagocyte System by Poloxamine 908: Its Implications for Targeted Drug Delivery

Purpose. To investigate the effect of poloxamine 908 on the MPS activity and the importance of its mode of presentation to the immune system. Methods. Solutions of endotoxin free poloxamine 908 were injected daily intravenously to rats, and the effect on the degree of sequestration by the liver of I¹²⁵ labelled, poloxamine 908-coated 60 nm polystyrene particles was investigated by studying effect of dosing regimen(s) and assessment of opsonic activity. Results. After 3 or 4 days repeated dosing with poloxamine 908 (0.7 mg) in solution, the poloxamine 908-coated polystyrene particles (60 nm) were rapidly cleared from the circulation. The increased sequestration of the particles by the liver lasted for more than 7 days after last dosing with the poloxamine 908 solution. In subsequent studies, it was found that a single dose of poloxamine 908 (0.7 mg) in solution was sufficient to activate the MPS 4 days after the injection. The increased uptake was found not be mediated by a serum component, nor was it due to proliferation of the Kupffer cells in the liver. Conclusions. The results provide evidence that a solution of endotoxin-free poloxamine 908 activates the MPS so that 4 days after injection otherwise long-term circulating poloxamine 908-coated particles are sequestered by the liver. This finding has implications for use of such coated systems in therapeutic situations.     

Preparation of Multiparticulate Vaginal Tablet Using Glyceryl Monooleate for Sustained Progesterone Delivery

Most of the sustained release vaginal formulations are in the form of bioadhesive gels and tablets. Though proved efficient, their presence in the vagina for a longer time as a bulk produces discomfort and interference with body functioning including sexual activities. Hence, they lack complete patient compliance. In this study, multiparticulate vaginal tablets were prepared by utilizing progesterone (PRO) loaded dry powder precursor of cubic phase (DPPCP) of glyceryl monooleate (GMO). DPPCP were obtained by spray drying GMO with magnesium trisilicate (MTS) and have presented PRO sustained release in simulated vaginal fluid (SVF) for 14 hours. The effect of hydrophilic and hydrophobic tableting excipients on compression, phase, bioadhesion and drug release properties of prepared tablets was evaluated. The effervescent hydrophilic tablet (EHT) prepared with hydrophilic excipients showed rapid disintegration but, diminished sustaining ability owing to transformation into lamellar phase whereas the multiparticulate hydrophobic tablet (MHT) obtained from hydrophobic excipients presented both rapid disintegration and sustained release in SVF by virtue of cubic phase retention. During bioadhesivity testing, fast disintegration of MHT with formation of uniform and viscous bioadhesive layer on cow mucosa was observed even with a small volume of SVF. As MHT may not produce discomfort and interference, it will be preferred over bioadhesive gel or tablet.     

抗肿瘤抗体偶联药物靶向递送的研究进展

抗体与抗原结合的靶向递送是一种精准的递药方式,由于其高特异性和亲和力被视为理想的靶向递药方式之一,这为成功解决抗肿瘤治疗中化疗药物选择性差的问题开辟了新的道路。当前,利用单克隆抗体与靶抗原结合的抗体偶联药物(antibody drug conjugates,ADCs)研究成为分子靶向治疗的研究热点,本文就ADCs靶向递送的作用机制、靶向策略和靶向递送进展进行综述,以期为临床开发新的ADCs提供参考。     

免疫脂质体作为靶向给药系统的研究进展

免疫脂质体是用抗体或其片段修饰的脂质体,能与靶细胞表面抗原或受体结合,从而对靶细胞具有分子水平上的识别能力。与游离药物、非特异抗体脂质体、单独单抗等相比,免疫脂质体有更好的选择性和更强的杀伤活性。在动物体内,免疫脂质体可使药物特异性分布在病灶部位,从而增强药物疗效、减轻不良反应,并且表面聚乙二醇化还增强了体内的循环时间。本文综述了用于修饰的不同种类抗体、抗体与免疫脂质体偶联方式,并总结了免疫脂质体在抗肿瘤药、基因治疗、活体成像技术以及在传染病、自身免疫和神经退行性疾病治疗方面的应用。     

Targeted Drug Delivery for Boron Neutron Capture Therapy

Purpose. Boron neutron capture therapy (BNCT) is a form of radiochemotherapy that is becoming increasingly important for the treatment of malignant gliomas, malignant melanomas and other forms of cancer. Targeted delivery of boron to tumors is a critical prerequisite for successful BNCT. Methods. Strategies that involve synthetic chemical approaches and biochemical and biophysical approaches are employed to meet this requirement. Compounds developed for targeting to tumors include borocaptate sodium (BSH) and p-boronophenylalanine (BPA) which are currently in clinical use. Results. Boronated porphyrins, nucleosides, nucleotides and other boronated compounds show potentials as targeting molecules. Conjugation of boron compounds to macromolecules such as monoclonal antibodies, epidermal growth factor and dextran is also employed for active or passive tumor targeting. Conclusions. Boron delivery via microparticulate carriers such as liposomes, high density lipoproteins and microcapsules is also attractive for its potential application in BNCT.     

口服结肠释药系统的研究进展

目的:综述近年来口服结肠释药系统临床和药学研究动态,为今后在此领域的研究和临床应用提供参考。方法:通过对国内外相关文献资料的整理,对比和分析,总结口服结肠释药系统制剂进展和临床应用的发展方向。结果结论:口服结肠释药系统是通过口服给药,在结肠处定位释放药物的靶向制剂。此类制剂以其靶向释药方式和独特的临床使用价值,越来越广泛地引起了临床医生的关注,同时也成为药学研究领域的一大热点。     

Colonic Drug Delivery: Prodrug Approach

The colon is largely being investigated as a site for administration of protein and peptides, which are degraded by digestive enzymes in the upper GIT. Also for local diseases of the colon, drug administration to the site of action can not only reduce the dose to be administered, but also decrease the side effects. One of the approaches used for colon specific drug delivery is the formation of a prodrug which optimizes drug delivery and improves drug efficacy. Many prodrugs have been evaluated for colon drug delivery. These prodrugs are designed to pass intact and unabsorbed from the upper GIT and undergo biotransformation in the colon releasing the active drug molecule. This biotransformation is carried out by a variety of enzymes, mainly of bacterial origin present in the colon (e.g. azoreductase, glucuronidase, glycosidase, dextranase, esterase, nitroreductase, cyclodextranase, etc.). The present review includes varius prodrug approaches investigated for colon drug delivery and their site specificity.     

果胶在细菌触发型结肠定位给药制剂中的应用

综述了近年来果胶在细菌触发型结肠定位给药制剂中的应用进展。果胶在胃和小肠部位不降解,但能被结肠细菌酶降解,故以果胶为载体,通过包衣、制成骨架、合成前药及与钙交联等方法制备结肠定位给药制剂,有良好的应用前景。     

The Effect of Meal Composition on the Gastrocolonic Response: Implications for Drug Delivery to the Colon

The response of the colon to eating, the gastrocolonic response (GCR), may have important implications for the design of drug dosage forms for selective delivery to the colon. Therefore, the effect of meal composition on the GCR and its relation to the transit of non-disintegrating tablets has been investigated. Eight healthy male volunteers each received 5 × 6-mm radiolabeled nondisintegrating tablets, and the transit was followed using a gamma camera. When the tablets reached the ileocolonic region, each volunteer received a test meal (1000 kcal) containing 70% carbohydrate, 15% fat, and 15% protein. The subsequent movement of the tablets was then monitored. The study was repeated using a 70% fat meal and a 70% protein meal, so that the effects of a high-carbohydrate, a high-fat, and a high-protein meal on the GCR could be compared. The incidence of GCRs was similar after all meals. Thus, there appeared to be no effect of meal composition on the movement of the tablets into the colon. This implies that the ingestion of food may not necessarily stimulate the passage of material across the ileocecal junction and that other factors may also be involved.     

脑靶向给药系统的研究进展

介绍了近年来脑靶向给药的研究进展，为研制可透过血－脑屏蔽的治疗中枢神经系统疾病的脑内给药系统提供参考。     

生物素在肿瘤靶向递药中的研究进展

运用靶向递药系统给药是目前治疗癌症的有效方法,靶向配体的选择是靶向递药的关键。生物素受体在多数肿瘤细胞表面过表达,但在正常细胞中低表达或不表达,因此,生物素可作为配体与药物载体相连,用于肿瘤靶向递药。简述生物素及生物素受体,综述生物素修饰的脂质体、胶束、纳米粒等载药系统在肿瘤靶向诊断和治疗中的研究进展,以期为相关研究开发与临床应用提供参考。     

增塑剂及热处理对水性包衣美沙拉秦结肠靶向微丸体外释药 …

以乙基纤维素水分散体Ａｑｕａｃｏａｔ为包衣材料,制备延迟释药的美沙拉秦结肠靶向微丸,考察了４种塑塑剂（三乙酸甘油酯,癸二酯二丁酯、梅楷酸三乙酯、邻苯二甲酸二乙酯）和热处理时间对微丸释药的影响。结果显示,以枸楷酸三乙酯塑化微丸的释药最为理想,在延迟３～４ｈ后开始释药,１２内释药完全,于６０℃处理４ｈ后,释药即趋于稳定。