靶向给药在各脏器的研究进展

靶向制剂是以药物能在疾病靶区浓集为主要特点的一大类制剂的总称,最突出的特点是能将治疗药物最大限度地运送到靶区,使治疗药物在靶区浓集超出传统的数倍乃至数百倍,治疗效果明显提高,同时减少药物的用量,降低药物不良反应,而且便于控制给药的速度和方式,达到高效低毒达到治疗效果。近年来靶向给药的研究取得了令人鼓舞的进展,本文针对近几年靶向给药在各脏器的研究进展进行综述,以了解靶向给药在各脏器的应用现状。     

肝靶向给药系统的研究进展

通过对近年来国内外报道的肝靶向研究相关文献进行检索,根据肝靶向药物的不同作用机制对肝靶向给药系统的研究进展进行分析和总结。有关肝靶向药物的研究结果表明,肝靶向给药系统能选择性地将药物输送至肝脏病变部位,通过提高其在肝脏病变组织的药物浓度,从而达到增强药物疗效、减少其毒副作用的目的。因此,肝靶向给药系统在肝脏疾病治疗方面具有广阔的应用前景。     

磁性靶向药物的研究进展

磁性靶向药物是利用大分子物质包被磁性纳米粒子，携带抗肿瘤药物，利用体外磁场实现定向治疗的给药方式。靶向给药是一种比较理想的给药方式，属于第4代药物剂型。综述磁性靶向药物的分类，分别介绍磁性粒子和磁性靶向药物的制备方法和体外磁场所采用的形式。由于某些技术未获得突破，所以磁性靶向给药系统现在仍处于实验研究阶段，真正应用于临床还有待进一步研究。     

肿瘤靶向给药系统的临床应用进展

目的对抗肿瘤靶向给药系统的研究进展作一简介。方法检索近年国内外有关对靶向给药系统在肿瘤治疗中的研究性文献,并进行分析、归纳,综述肿瘤组织靶向、肿瘤细胞靶向、肿瘤血管靶向等给药系统及肿瘤靶向治疗基因给药系统的研究进展,以完善现有肿瘤的靶向治疗。结果靶向药物制剂能使药物选择性地与靶组织在细胞或亚细胞水平上发生反应,使药物能够可控性地分布,并于靶区持续缓慢地释放药物,降低其对正常组织的不良反应。结论靶向制剂对于克服肿瘤治疗中的不良反应,提高疗效具有不可忽视的作用,但它们广泛应用于临床尚需时日。     

靶向给药在盆腔炎治疗中的应用

靶向给药被称为第四代给药方法,是指将极少量药物直接定位于靶区(患部)使靶区药物浓度高于其他正常组织,提高疗效、降低全身毒副作用[1].患者易于接受,无痛苦,无不良反应.我科采用靶向给药方法治疗盆腔炎308例,效果优于传统治疗.     

口服结肠靶向纳米载体的研究进展

通过对近年来有关口服结肠靶向给药纳米载体的文献进行归纳和总结,列出了常用的新型口服结肠靶向纳米给药载体如纳米粒、纳米乳、胶束、脂质体纳米凝胶和纳米混悬液等。结肠靶向纳米载体可使药物选择性到达结肠部位,减少给药剂量、降低药物毒副作用,从而提高药物口服生物利用度,发挥治疗结肠相关疾病的作用。     

口服结肠给药系统的研究进展

口服结肠靶向给药系统(oral colon targetting drug deliv-ery system,OCTDDS))将治疗结肠疾病的药物靶向输送至结肠,不仅降低常规的口服或直肠给药的毒副作用,且能将药物输送至病灶处,减少给药剂量,提高患者的顺应性;还能提高多肽、蛋白等类药物口服给药的生物利用度。笔者将近年有关口服结肠给药系统的研究综述如下。1口服结肠释药系统的应用1.1时控给药根据时辰药理学原理,应用药剂手段使药物在一定的时滞后释放,使之与人的生理周期相匹配,可用于治疗哮喘、高血压、心绞痛、消化道溃疡及风湿性关节炎等具有节律性的疾病。结肠靶向给药…     

结肠吸收及结肠靶向给药

目的：对目前结肠吸收及其靶向给药方面的研究进行综述。方法：讨论药物结肠吸收特点和结肠靶向给药方法。结果：结肠是多肽药物口服的最佳吸收部位和缓控释制度口服持续吸收的重要部位。结肠靶向制剂可用于结肠局部病患的治疗和多肽药物的口服给药。结论：结肠吸收及其靶向给药是有意义而又有许多有待研究的领域。     

肿瘤靶向治疗药物的评价

近年来，肿瘤靶向药物治疗已经引起人们高度重视。所谓靶向药物治疗就是使药物瞄准肿瘤部位。在局部保存相对高的浓度，延长药物作用时间。提高对肿瘤的杀伤力，而对正常组织细胞作用较小。目前，用于肿瘤靶向治疗的药物有控缓释化疗药、脂质体化疗药、分子靶向药物等。药物可通过多条途径给予，如血管介入给药、超声介导靶向经皮给药等。     

脑靶向给药的主要方式及其应用

由于血脑屏障的存在，大脑给药受到了严格控制。为使药物更专一地靶向至大脑，科学家们采取了多种办法。本文综述了治疗大脑疾病的靶向给药系统的2种方式：基于化学方法和生物学方法的脑靶向给药系统，以及它们在治疗大脑疾病方面的应用，为脑部给药的研究提供了依据。     

冬凌草甲素靶向给药系统研究进展

目的介绍冬凌草甲素靶向制剂的研究现状。方法综述近年来国内外相关研究,介绍靶向制剂靶向原理和特性、药动药效学研究进展,并对其可行性和前景进行分析。结果冬凌草甲素靶向制剂不仅可以提高冬凌草甲素的溶解度,而且提高了靶部位药物浓度,增强抗肿瘤效果、降低不良反应。结论开发更高靶向效率、安全、经济、多类型的给药系统是未来冬凌草甲素靶向制剂的研究焦点。     

聚合物胶束作为药物载体及其在肿瘤靶向方面的研究进展

聚合物胶束具有粒径小、稳定性高、滞留时间长、良好的生物相容性等特点,这些优良性质使得聚合物胶束作为药物载体具有许多独特的优势。近年来,涌现了许多围绕聚合物胶束设计肿瘤靶向给药系统的报道,包括利用肿瘤的病理学性质,设计被动靶向给药系统和对聚合物胶束进行表面修饰,设计主动靶向给药系统。本文主要综述了聚合物胶束作为肿瘤靶向药物载体的研究进展。     

Nanocarriers for cancer-targeted drug delivery

Nanoparticles as drug delivery system have received much attention in recent years, especially for cancer treatment. In addition to improving the pharmacokinetics of the loaded poorly soluble hydrophobic drugs by solubilizing them in the hydrophobic compartments, nanoparticles allowed cancer specific drug delivery by inherent passive targeting phenomena and adopted active targeting strategies. For this reason, nanoparticles-drug formulations are capable of enhancing the safety, pharmacokinetic profiles and bioavailability of the administered drugs leading to improved therapeutic efficacy compared to conventional therapy. The focus of this review is to provide an overview of various nanoparticle formulations in both research and clinical applications with a focus on various chemotherapeutic drug delivery systems for the treatment of cancer. The use of various nanoparticles, including liposomes, polymeric nanoparticles, dendrimers, magnetic and other inorganic nanoparticles for targeted drug delivery in cancer is detailed.     

Biodegradable polymers for targeted delivery of anti-cancer drugs

ABSTRACT

Introduction: Biodegradable polymers have been used for more than three decades in cancer treatment and have received increased interest in recent years. A range of biodegradable polymeric drug delivery systems designed for localized and systemic administration of therapeutic agents as well as tumor-targeting macromolecules has entered into the clinical phase of development, indicating the significance of biodegradable polymers in cancer therapy.

Areas covered: This review elaborates upon applications of biodegradable polymers in the delivery and targeting of anti-cancer agents. Design of various drug delivery systems based on biodegradable polymers has been described. Moreover, the indication of polymers in the targeted delivery of chemotherapeutic drugs via passive, active targeting, and localized drug delivery are also covered.

Expert opinion: Biodegradable polymer-based drug delivery systems have the potential to deliver the payload to the target and can enhance drug availability at desired sites. Systemic toxicity and serious side effects observed with conventional cancer therapeutics can be significantly reduced with targeted polymeric systems. Still, there are many challenges that need to be met with respect to the degradation kinetics of the system, diffusion of drug payload within solid tumors, targeting tumoral tissue and tumor heterogeneity.     

主动靶向脂质体研究进展

目的 介绍主动靶向脂质体最新研究进展。方法 查阅近年来国内外相关文献,对主动靶向脂质体的表面修饰、配体选择及应用进行进行总结和归纳。结果 主动靶向脂质体的表面修饰有三种方法：作为组份直接制备;键合到脂质体表面;后插入法。主动靶向脂质体可以将药物传递到靶组织、靶向细胞或靶细胞器,提高药物的生物利用度,而不增加对正常组织或细胞的毒性,是近年研究最为广泛的主动靶向给药系统。结论 主动靶向脂质体是一种非常有前途的给药系统。     

包合物脂质体靶向系统在给药中的应用

近年来,包合物和脂质体作为药物的载体被广泛用于药物制剂领域,各自发挥着自身的优势。将环糊精包合物应用于脂质体给药系统——这一新型的药物载体,能够更好地提高靶向给药效果。本文通过概述包合物及脂质体的优势,阐明包合物脂质体这一新型给药系统能提高药物的载药量,增加脂质体的稳定性,对提高药物的吸收和临床疗效等方面具有重要意义,对于靶向给药系统的进一步发展具有新的参考价值。     

Role of polymer–drug conjugates in organ-specific delivery systems

Polymers have been utilized to deliver the drug to targeted site in controlled manner, achieving the high-therapeutic efficacy. Polymeric drug conjugates having variable ligands as attachments have been proved to be biodegradable, stimuli sensitive and targeted systems. Numerous polymeric drug conjugates having linkers degraded by acidity or intracellular enzymes or sensitive to over expressed groups of diseased organ/tissue have been synthesized during last decade to develop targeted delivery systems. Most of these organs have number of receptors attached with different cells such as Kupffer cells of liver have mannose-binding receptors while hepatocytes have asialoglycoprotein receptors on their surface which mainly bind with the galactose derivatives. Such ligands can be used for achieving high targeting and intracellular delivery of the drug. This review presents detailed aspects of receptors found in different cells of specific organ and ligands with binding efficiency to these specific receptors. This review highlights the need of further studies on organ-specific polymer–drug conjugates by providing detailed account of polymeric conjugates synthesized till date having organ-specific targeting.     

Engineering a folic acid-decorated ultrasmall gemcitabine nanocarrier for breast cancer therapy: Dual targeting of tumor cells and tumor-associated macrophages

Combination of passive targeting with active targeting is a promising approach to improve the therapeutic efficacy of nanotherapy. However, most reported polymeric systems have sizes above 100 nm, which limits effective extravasation into tumors that are poorly vascularized and have dense stroma. This will, in turn, limit the overall effectiveness of the subsequent uptake by tumor cells via active targeting. In this study, we combined the passive targeting via ultra-small-sized gemcitabine (GEM)-based nanoparticles (NPs) with the active targeting provided by folic acid (FA) conjugation for enhanced dual targeted delivery to tumor cells and tumor-associated macrophages (TAMs). We developed an FA-modified prodrug carrier based on GEM (PGEM) to load doxorubicin (DOX), for co-delivery of GEM and DOX to tumors. The co-delivery system showed small particle size of ～10 nm in diameter. The ligand-free and FA-targeted micelles showed comparable drug loading efficiency and a sustained DOX release profile. The FA-conjugated micelles effectively increased DOX uptake in cultured KB cancer cells that express a high level of folate receptor (FR), but no obvious increase was observed in 4T1.2 breast cancer cells that have a low-level expression of FR. Interestingly, in vivo, systemic delivery of FA-PGEM/DOX led to enhanced accumulation of the NPs in tumor and drastic reduction of tumor growth in a murine 4T1.2 breast cancer model. Mechanistic study showed that 4T1.2 tumor grown in mice expressed a significantly higher level of FOLR2, which was selectively expressed on TAMs. Thus, targeting of TAM may also contribute to the improved in vivo targeted delivery and therapeutic efficacy.     

pH敏感型纳米递药系统在肿瘤靶向治疗中的作用

目的 综述目前pH敏感纳米递药系统用于肿瘤靶向治疗中的国内外研究进展。方法 在Pubmed和Google上检索近年国内外资料,阐明pH敏感纳米递药系统靶向肿瘤治疗的作用机制,对超顺磁性纳米粒、胶束、树状大分子等相关研究成果进行总结和评价。结果 传统肿瘤化疗药物普遍存在疗效低、副作用大等问题,而近年来研发的pH响应的纳米载体可通过EPR效应积聚于肿瘤组织,并在弱酸性的肿瘤细胞外液或经内吞作用后在细胞质或溶酶体中释放药物。该pH敏感型载体能促进药物的靶向递送,在减少系统性副作用的同时提高肿瘤化疗疗效。结论 pH敏感纳米递药系统在肿瘤靶向治疗中具有广阔的应用前景,开发具有靶向性、高效性、安全性的递药系统是目前该领域研究主要方向之一。     

Selective Adhesion of Nanoparticles to Inflamed Tissue in Gastric Ulcers

Purpose  Gastrointestinal deposition of nanoparticles was examined after oral administration to mice suffering from an experimental gastric ulcer model. Local drug delivery could reduce side effects and would be a distinct improvement compared to existing therapeutic approaches, e.g. in the local therapy of Helicobacter pylori. Methods  A gastric ulcer was induced to Swiss mice by acetic acid injection. Fluorescent polystyrene particles with a nominal size of 50, 200, and 750 nm were administered orally for 3 or 5 days and particle adhesion in the gastrointestinal tract analyzed. Results  In the ulcerated regions, an enhanced particle adhesion was observed compared to healthy controls. A size dependency of the deposition was found which further increased with a prolonged treatment period. For 750 nm particles only fair adhesion was observed (control, 2.0 ± 1.4%; ulcer, 4.5 ± 0.7% of daily administered particle mass), while already 200 nm particles showed higher binding (control, 2.9 ± 1.3%; ulcer, 7.8 ± 1.2%). Highest relative adhesion was found for 50 nm particles (control, 2.8 ± 1.3%; ulcer, 10.0 ± 1.5%). The targeting index of gastric ulcer versus healthy control was nearly constant around 2 after 3 days treatment, but increased distinctly for smaller particles after 5 days. Conclusions  The use of sub-micron sized carriers holds promise for the targeted delivery of drugs to the ulcerated mucosal areas in the stomach. An erratum to this article can be found at