姜黄素纳米制剂抗消化系统肿瘤的药理作用研究进展

姜黄素（curcumin）是从姜黄中提取的多酚化合物,具有抗肿瘤、抗炎、抗菌等广泛的药理活性,但其溶解度低、生物利用度差、药动学差,限制了该药的临床应用。近年来,基于纳米技术的药物递送系统（主要包括纳米颗粒、脂质体、胶束、聚合物、纳米凝胶等）有效改善了姜黄素的生物利用度和溶解性,提高了体内药物活性。就姜黄素纳米制剂在消化系统肿瘤（胃癌、肝癌、结直肠癌、胰腺癌和食管癌）中的应用进行综述,旨在为姜黄素纳米制剂的进一步研究与利用提供参考。     

姜黄素类化合物的研究进展

姜黄素作为中药姜黄的主要活性成分,对炎症、肿瘤、代谢类疾病和神经系统疾病均显示良好的应用前景,因其生物利用度低限制了临床应用。围绕姜黄素的结构修饰一直是药物学家的兴趣所在。本文就近五年姜黄素类化合物研究进展进行综述,为开发姜黄素类药物提供参考。     

磁性氧化铁纳米粒子的神经毒性研究进展

磁性氧化铁纳米粒子（MION）作为一种重要的纳米材料,因其特殊性质（如磁性、较好的生物相容性）在生物医药领域应用广泛,在与人脑相关的疾病诊断和治疗方面发挥重要作用。然而,MION在脑内的蓄积可能会导致潜在的神经毒性。从MION的表征、入脑方式、神经毒性效应以及神经毒性机制等方面概述了MION的神经毒性研究进展。目前,研究者对纳米毒理学中的神经毒理学还了解甚少,轻度或中度的神经毒性可能很微妙且难以检测。因此,对于MION这类可能入脑或用于诊断和治疗神经系统疾病的纳米药物,应深入探究其神经毒性作用机制,进而建立有效的安全性评价方法和策略,以指导临床合理用药。     

微载体药物递送系统在姜黄素中的应用研究进展

目的综述微载体药物递送系统在姜黄素中的应用研究进展,进一步了解姜黄素的研究概况。方法分别介绍姜黄素的纳米粒、微球、微乳、微囊、胶束、脂质体、磷脂复合物、环糊精包合物等递送系统的研究进展。结果微载体药物递送系统被广泛的应用于提高姜黄素的溶解度和稳定性,进而提高药物在体内的生物利用度。结论微载体药物递送系统在姜黄素中的应用研究为姜黄素进一步应用于临床提供研究基础。     

胆红素纳米颗粒的药理作用研究进展

胆红素具有良好的抗炎、抗氧化和免疫调节作用，但由于其水溶性差、生物利用度低，极大地限制了临床应用。研究人员将胆红素开发成各种纳米颗粒，借助剂型优势有效消除了胆红素溶解性低的限制，使其能够最大化地发挥抗炎、抗氧化、调节免疫等药理活性。胆红素纳米颗粒在多种胃肠道疾病、肝肾疾病、皮肤疾病、自身免疫性疾病、胰岛移植以及肿瘤的靶向治疗（既可直接抗肿瘤，又可作为药物递送系统）中均具有巨大的应用潜力。对胆红素纳米制剂的研究将推动胆红素的临床应用和相关的新药研发。     

姜黄素纳米乳的体内外药动学研究

目的 研究姜黄素纳米乳的体内外药动学,并与游离的药物比较.方法 用透析法考察姜黄素纳米乳体外释放药物的特点,建立大鼠模型研究其在体内的吸收情况.结果 姜黄素纳米乳和游离姜黄素在0.1 mol·L-1盐酸和pH6.8磷酸缓冲溶液中的释药符合Higuchi模型,纳米乳的释放曲线在各种释放介质中与游离药物的相似因子均小于50;而姜黄素纳米乳的Ka和Papp在不同肠段与游离药物的相比均提高了约2倍,AUC(0-72)约是游离药物的4倍.结论 姜黄素纳米乳较游离药物提高了药物的生物利用度.     

PCL-PEG-PCL载姜黄素纳米粒子的制备以及体外药物释放的考察

目的制备一种生物可降解、生物相容性良好的姜黄素纳米粒子,并对其体外药物释放行为进行考察。方法采用开环聚合法制备生物可降解的PCL-PEG-PCL三嵌段聚合物,然后采用乳液挥发法制备负载姜黄素的PCL-PEG-PCL纳米粒子,通过透射电镜观察所制备纳米粒子的形貌特征,动态光散射(DLS)测定粒径,采用HPLC测定纳米粒子的包封率和载药量,同时考察其体外药物释放行为。结果姜黄素纳米粒子具有球形结构,粒径在200 nm左右,载药量为(14.23±0.35)%,3 d体外累积释药量65%。结论所制备的姜黄素纳米粒子具有较高的载药量和包封率,同时体外药物释放实验证实姜黄素纳米粒子具有良好的缓释功能。     

姜黄素抗肿瘤作用基础与临床研究进展

姜黄素是中药姜黄根茎的主要活性成分,是一种疏水性多酚,具有广泛的生物和药理活性,可用于治疗肿瘤、糖尿病、炎症、神经退行性疾病、心血管疾病、代谢综合征和肝病等,其中姜黄素的抗肿瘤作用更是受到了广泛的关注。本文主要综述了姜黄素的抗肿瘤作用及其机制,如靶向调节肿瘤细胞周期、抑制血管生成、促进肿瘤细胞凋亡等信号通路和相关靶点,姜黄素的药物代谢和代谢产物、结构修饰及衍生物、新型药物递送系统,以及姜黄素的临床研究现状,包括姜黄素与化疗药物联合应用的基础和临床研究进展。希望通过综述姜黄素的基础和临床研究现状,以揭示其临床应用前景,也为其相关领域的进一步研究提供参考。     

先天免疫受体介导的神经炎症在神经系统疾病中的作用

神经退行性疾病、精神疾病和脑损伤等多种神经系统疾病的发生与神经炎症密切相关。先天免疫受体是脑内免疫防御的第一道防线,在神经炎症和神经系统疾病的发生发展过程中起到至关重要的作用。本综述重点围绕参与神经免疫的先天免疫受体,从先天免疫受体类型、功能作用和分子机制等几方面,详细阐述先天免疫受体介导的神经炎症在神经系统疾病中的功能作用和分子机制。同时,简要概述目前治疗神经退行性疾病药物的研究进展,以及靶向神经炎症的药物开发和临床治疗的可行性。     

姜黄素对药物代谢酶和转运体影响的研究进展

姜黄素(curcurmin,Cur)是传统药物姜黄的主要有效成分,生活中可作为调料和食物染色剂。大量研究证明姜黄素有许多重要的生物学作用,包括抗炎、抗氧化、抗癌、促进伤口愈合、防治心血管疾病和神经系统退变性疾病等[1-2],     

Conundrum and therapeutic potential of curcumin in drug delivery

Turmeric, the source of the polyphenolic active compound curcumin (diferuloylmethane), has been used extensively in traditional medicine since ancient times as a household remedy against various diseases, including hepatic disorders, cough, sinusitis, rheumatism, and biliary disorders. In the past few decades, a number of studies have been done on curcumin showing its potential role in treating inflammatory disorders, cardiovascular disease, cancer, AIDS, and neurological disorders. However, the main drawback associated with curcumin is its poor aqueous solubility and stability in gastrointestinal fluids, which leads to poor bioavailability. Multifarious novel drug-delivery approaches, including microemulsions, nanoemulsions, liposomes, solid lipid nanoparticles, microspheres, solid dispersion, polymeric nanoparticles, and self-microemulsifying drug-delivery systems have been used to enhance the bioavailability and tissue-targeting ability of curcumin. These attempts have revealed promising results for enhanced bioavailability and targeting to disease such as cancer, but more extensive research on tissue-targeting and stability-related issues is needed. Tissue targeting and enhanced bioavailability of curcumin using novel drug-delivery methods with minimum side effects will in the near future bring this promising natural product to the forefront of therapy for the treatment of human diseases such as cancer and cardiovascular ailments. We provide a detailed analysis of prominent research in the field of curcumin drug delivery with special emphasis on bioavailability-enhancement approaches and novel drug-delivery system approaches.     

Therapeutic Applications of Curcumin Nanoformulations

Curcumin (diferuloylmethane) is a bioactive and major phenolic component of turmeric derived from the rhizomes of curcuma longa linn. For centuries, curcumin has exhibited excellent therapeutic benefits in various diseases. Owing to its anti-oxidant and anti-inflammatory properties, curcumin plays a significant beneficial and pleiotropic regulatory role in various pathological conditions including cancer, cardiovascular disease, Alzheimer’s disease, inflammatory disorders, neurological disorders, and so on. Despite such phenomenal advances in medicinal applications, the clinical implication of native curcumin is hindered due to low solubility, physico-chemical instability, poor bioavailability, rapid metabolism, and poor pharmacokinetics. However, these issues can be overcome by utilizing an efficient delivery system. Active scientific research was initiated in 2005 to improve curcumin’s pharmacokinetics, systemic bioavailability, and biological activity by encapsulating or by loading curcumin into nanoform(s) (nanoformulations). A significant number of nanoformulations exist that can be translated toward medicinal use upon successful completion of pre-clinical and human clinical trials. Considering this perspective, current review provides an overview of an efficient curcumin nanoformulation for a targeted therapeutic option for various human diseases. In this review article, we discuss the clinical evidence, current status, and future opportunities of curcumin nanoformulation(s) in the field of medicine. In addition, this review presents a concise summary of the actions required to develop curcumin nanoformulations as pharmaceutical or nutraceutical candidates.KEY WORDS: cancer, curcumin, drug delivery, nanoparticles, nanotechnology     

西红花苷防治中枢神经系统疾病的研究进展

西红花苷是西红花中活性成分，具有多种药理作用。西红花苷具有出色的中枢神经系统保护作用，可以多维度、多途径地改善中枢神经系统疾病的神经功能，能抗抑郁、抗癫痫，对帕金森病、阿尔茨海默病、缺血性脑卒中、多发性硬化具有神经保护作用。综述了西红花苷防治中枢神经系统疾病的研究进展，以期提高西红花苷在临床治疗中的转化和应用。     

Bovine serum albumin nanoparticles improve the antitumour activity of curcumin in a murine melanoma model

Abstract

Curcumin is a natural compound presenting important antitumour activity. However, due to its low aqueous solubility, instability at physiological pH, and low oral bioavailability, its clinical use is limited. Bovine serum albumin (BSA) nanoparticles have been used as drug carriers to improve the drug properties. In this work, curcumin-loaded BSA nanoparticles were developed and the in vitro cytotoxicity over murine melanoma cells and the in vivo antitumour activity in a murine melanoma model were assessed. Nanoparticles presented 150?nm, polydispersity index of 0.16, negative zeta potential, and 45% of curcumin encapsulation efficiency. Curcumin release from nanoparticles was slow and diffusion dependent. In the cytotoxicity assay, free curcumin was more efficient than curcumin-loaded nanoparticles, probably due to the prolonged curcumin release from nanoparticles. However, in a murine melanoma model, curcumin-loaded nanoparticles presented higher antitumour efficiency than free curcumin. BSA nanoparticles are efficient curcumin carriers that may have relevant applications in melanoma treatment.     

Bioavailability of curcumin: problems and promises

Curcumin, a polyphenolic compound derived from dietary spice turmeric, possesses diverse pharmacologic effects including anti-inflammatory, antioxidant, antiproliferative and antiangiogenic activities. Phase I clinical trials have shown that curcumin is safe even at high doses (12 g/day) in humans but exhibit poor bioavailability. Major reasons contributing to the low plasma and tissue levels of curcumin appear to be due to poor absorption, rapid metabolism, and rapid systemic elimination. To improve the bioavailability of curcumin, numerous approaches have been undertaken. These approaches involve, first, the use of adjuvant like piperine that interferes with glucuronidation; second, the use of liposomal curcumin; third, curcumin nanoparticles; fourth, the use of curcumin phospholipid complex; and fifth, the use of structural analogues of curcumin (e.g., EF-24). The latter has been reported to have a rapid absorption with a peak plasma half-life. Despite the lower bioavailability, therapeutic efficacy of curcumin against various human diseases, including cancer, cardiovascular diseases, diabetes, arthritis, neurological diseases and Crohn's disease, has been documented. Enhanced bioavailability of curcumin in the near future is likely to bring this promising natural product to the forefront of therapeutic agents for treatment of human disease.     

An Overview of Curcumin in Neurological Disorders

Curcumin, the principal curcuminoid found in spice turmeric, has recently been studied for its active role in the treatment of various central nervous system disorders. Curcumin demonstrates neuroprotective action in Alzheimer''s disease, tardive dyskinesia, major depression, epilepsy, and other related neurodegenerative and neuropsychiatric disorders. The mechanism of its neuroprotective action is not completely understood. However, it has been hypothesized to act majorly through its anti-inflammatory and antioxidant properties. Also, it is a potent inhibitor of reactive astrocyte expression and thus prevents cell death. Curcumin also modulates various neurotransmitter levels in the brain. The present review attempts to discuss some of the potential protective role of curcumin in animal models of major depression, tardive dyskinesia and diabetic neuropathy. These studies call for well planned clinical studies on curcumin for its potential use in neurological disorders.     

Advances in brain drug targeting and delivery: limitations and challenges of solid lipid nanoparticles

Introduction: With the advancement in the field of medical colloids and interfacial sciences, the life expectancy has been greatly improved. In addition, changes in the human lifestyle resulted in development of various organic and functional disorders. Central nervous system (CNS) disorders are most prevalent and increasing among population worldwide. The neurological disorders are multi-systemic and difficult to treat as portal entry to brain is restricted on account of its anatomical and physiological barrier.

Areas covered: The present review discusses the limitations to CNS drug delivery, and the various approaches to bypass the blood brain barrier (BBB), focusing on the potential use of solid lipid nanoparticles (SLN) for drug targeting to brain. The methods currently in use for SLN production, physicochemical characterization and critical issues related to the formulation development suitable for targeting brain are also discussed.

Expert opinion: The potential advantages of the use of SLN over polymeric nanoparticles are due to their lower cytotoxicity, higher drug loading capacity and scalability. In addition, their production is cost effective and the systems provide a drug release in a controlled manner up to several weeks. Drug targeting potential of SLN can be enhanced by attaching ligands to their surface.     

Curcumin as potential therapeutic natural product: a nanobiotechnological perspective

Objectives

Nanotechnology‐based drug delivery systems can resolve the poor bioavailability issue allied with curcumin. The therapeutic potential of curcumin can be enhanced by making nanocomposite preparation of curcumin with metal oxide nanoparticles, poly lactic‐co‐glycolic acid (PLGA) nanoparticles and solid lipid nanoparticles that increases its bioavailability in the tissue.

Key findings

Curcumin has manifold therapeutic effects which include antidiabetic, antihypertensive, anticancer, anti‐inflammatory and antimicrobial properties. Curcumin can inhibit diabetes, heavy metal and stress‐induced hypertension with its antioxidant, chelating and inhibitory effects on the pathways that lead to hypertension. Curcumin is an anticancer agent that can prevent abnormal cell proliferation. Nanocurcumin is an improved form of curcumin with enhanced therapeutic properties due to improved delivery to the diseased tissue, better internalization and reduced systemic elimination.

Summary

Curcumin has multiple pharmacologic effects, but its poor bioavailability reduces its therapeutic effects. By conjugating curcumin to metal oxide nanoparticles or encapsulation in lipid nanoparticles, dendrimers, nanogels and polymeric nanoparticles, the water solubility and bioavailability of curcumin can be improved and thus increase its pharmacological effectiveness.     

鼻腔给药在神经系统疾病治疗中的研究进展

鼻腔给药可以避开血脑屏障、胃肠道降解和肝脏首过效应,经过嗅神经通路直接到达脑部,因而被用于多种神经系统疾病的治疗。本文综述了鼻腔解剖、鼻腔给药治疗中枢神经系统疾病的转运通路、作用机制、临床应用、面临挑战和新技术等方面的研究进展。     

Synthesis and Characterization of a Cytotoxic Cationic Polyvinylpyrrolidone–Curcumin Conjugate

Curcumin has been studied as a potential drug for many diseases including cancer. One of the serious limitations projected on curcumin is its poor water solubility and the substantially low bioavailability. With a view to enhance the aqueous solubility of curcumin, we synthesized polyvinylpyrrolidone–curcumin conjugates. Polyvinylpyrrolidone was used for the conjugation considering its long history of safe usage as a biomaterial for various medical applications. The drug conjugates self-assembled in aqueous solution to form nanosized micellar aggregates. The formation of micellae stabilized curcumin against hydrolytic degradation. Another interesting feature of the conjugate was its cationic nature. The net zeta potential in the pH range from 3 to 7.4 was +25 to +20 mV, reflecting the potential stability of the conjugate micellae at physiological pH. We quantified cytotoxic potential of the conjugate by the MTT assay, using L929 fibroblast cells. The results showed that the conjugate had higher cytotoxicity than that of the free curcumin. It is expected that the relative enhanced cytotoxicities are the result of enhanced aqueous solubility and polymer-mediated drug internalization. The conjugate has the potential to circumvent limitations of curcumin and thereby to extrapolate further its applications as an effective anticancer drug.