纳米粒作为抗肿瘤药物载体的研究进展

近年来纳米粒作为抗肿瘤药物载体的制备、作用机制及其体内外药效学评价等方面取得较大的进展.纳米粒作为抗肿瘤药物的载体具有许多优点,并可通过多种方式提高所携药物的药效学特征,显示纳米粒在肿瘤治疗领域具有广泛的应用前景.     

细胞膜修饰纳米粒药物递送系统的研究进展

纳米粒是药物递送系统研究的热点之一,但仍存在体内循环时间短,易被网状内皮系统识别和清除等缺点,限制了其临床应用。近年来,天然细胞膜成分和纳米技术的结合为解决这些问题提供了新的方案。一种由纳米粒核和细胞膜壳组成的新型仿生系统极大地改善了纳米粒的性能。用细胞膜修饰的纳米粒具有独特的功能,如延长血液循环时间,提高主动靶向和增强细胞内化等功能。本文综述了细胞膜修饰纳米粒药物递送系统的最新进展及其在癌症治疗方面的应用前景。     

壳聚糖纳米粒载体的应用研究进展

目的介绍壳聚糖纳米粒载体在药物、基因递送等方面的研究应用进展,为其在新领域的应用提供依据。方法广泛查阅中外文有关文献,整理分析归纳了其中27篇文献内容。结果壳聚糖纳米粒载体在药物和基因递送方面已经有诸多研究应用。结论壳聚糖纳米粒载体是一种有前途的非病毒递送载体,其特性和应用有待进一步探索。     

负载抗肿瘤药物的天然高分子纳米粒研究进展

具有生物相容性和生物可降解的天然高分子纳米粒近年来引起广泛关注.利用天然高分子纳米粒作为负载抗肿瘤药物靶向给药系统的研究正在快速发展,常见的有白蛋白纳米粒、明胶纳米粒、海藻酸钠纳米粒和壳聚糖纳米粒等.本文综述上述儿类纳米粒的特点、研究情况及发展趋势.     

阿霉素壳寡糖纳米粒的制备及体外抗肿瘤研究

目的制备负载阿霉素的壳寡糖纳米粒,并研究其理化性质和体外抗肿瘤细胞毒性。方法采用离子凝胶法制备负载阿霉素的壳寡糖纳米粒;透射电镜观察纳米粒形态,激光粒度仪测定粒径和表面电位,紫外分光光度法测量包封率、载药量,考察载药纳米粒的体外释药特性;采用MTT法对载药壳寡糖纳米粒在体外乳腺癌细胞株MCF-7的细胞毒作用进行评价。结果制得的阿霉素壳寡糖纳米粒呈球形或类球形,形态较为完整,平均粒径为(136.77±1.21)nm,表面电位为(20.53±0.31)m V,包封率为(56.99±1.40)%,载药量为(15.49±0.38)%,168 h的累积释放率为72.15%;阿霉素和载药纳米粒对MCF-7细胞增殖的抑制作用存在明显的浓度和时间依赖性,且载药纳米粒对MCF-7细胞增殖的抑制作用随时间增加而逐渐强于游离阿霉素。结论此方法制备的阿霉素壳寡糖纳米粒粒径较小,药物释放具有明显的缓释作用,并具有较好的抗肿瘤作用。     

基于丝素蛋白的纳米粒药物递送系统研究进展

丝素蛋白(silk fibroin, SF)是一种天然高分子,具有一定的水溶性、结构修饰性、良好的生物相容性和生物降解性,可作为药物递送的载体材料。SF载药纳米粒可控制药物释放、减少不良反应、提高治疗效果,是一种有前景的药物递送系统。本综述介绍了SF的基本特征、SF载药纳米粒的制备方法和SF在纳米粒药物递送系统的应用,在此基础上,对SF载药纳米粒的进一步发展进行了展望。     

磁性纳米粒在抗肿瘤药物中的应用

磁性纳米粒是一种新兴的正在迅速发展的新型材料,主要为铁氧体(γ-Fe2O3及Fe3O4)。由于其无毒无害,良好的生物相容性,目前在药物控制释放、肿瘤热疗以及智能开关等多个领域备受关注。本文结合近年来国内外对磁性纳米粒的研究报道,主要介绍了磁性纳米粒的性质及其在肿瘤药物缓控释中的应用等。希望能为其以后的研究和应用提供理论依据。     

磷脂-壳聚糖自组装纳米粒的研究进展

目的:了解磷脂-壳聚糖自组装纳米粒的研究进展,为新型药物递送载体的研究和开发提供思路。方法:以"壳聚糖""磷脂""纳米粒""自组装""Chitosan""Lecithin""Phospholipid""Nanoparticles""Self-assembled"等为关键词,在中国知网、万方、维普、PubMed、Elsevier、SpringerLink等数据库中组合查询2002年-2018年11月发表的相关文献,对磷脂-壳聚糖自组装纳米粒的形成机制和微观结构、制备方法以及作为药物递送载体的应用等相关研究进行综述。结果与结论:共检索到相关文献499篇,其中有效文献34篇。带正电荷的壳聚糖与磷脂中负电荷基团通过静电相互作用自组装形成脂溶性致密内核、壳聚糖包裹带正电荷水化外壳的核壳结构纳米粒;采用常规的溶剂注入法制得的磷脂-壳聚糖自组装纳米粒,具有良好生物相容性,能促进药物渗透吸收和提高生物利用度等,在口服、经皮、眼部及鼻腔黏膜等给药系统具有广泛的应用前景。今后可考虑对壳聚糖或纳米粒表面进行结构修饰和功能性设计,并进一步探索和研究如何精准调控自组装纳米粒的微观结构、尺寸大小、药物分布以及功能等。     

氧化苦参碱胶束纳米粒制备及其体外抗肿瘤活性研究

目的 制备氧化苦参碱胶束纳米粒并研究其体外抗肿瘤活性.方法 以遴选溶剂蒸发法与探头超声法对最优处方LP22进行理化性质、体外释药、稳定性以及体外抗肿瘤活性的初步考察.结果 处方LP22释药较慢,低于游离药物;粒径约200 nm;低质量浓度时抑制肿瘤细胞SMMC-7721活性强于氧化苦参碱溶液.结论 处方LP22具有一定缓释作用和肝靶向性,并显示出体外抗肿瘤活性.     

同轴静电喷雾法制备单分散载药纳米粒进展

同轴静电喷雾技术通过产生稳定的同轴喷射流体来制备核-壳结构的纳米粒,与传统工艺相比具有可精确控制粒径大小和分散系数、避免初始突释、制备条件温和等优势。通过改变同轴针头,同轴静电喷雾技术可以产生相应结构的载药纳米粒,满足药物递送的不同需求。本文介绍了用同轴静电喷雾法制备不同结构的载药纳米粒及扩大生产的研究现状。     

Calcium carbonate nanoparticles as cancer drug delivery system

Introduction: Calcium carbonate (CaCO₃) has broad biomedical utilizations owing to its availability, low cost, safety, biocompatibility, pH-sensitivity and slow biodegradability. Recently, there has been widespread interest in their application as drug delivery systems for different groups of drugs. Among them, CaCO₃ nanoparticles have exhibited promising potential as drug carriers targeting cancer tissues and cells. The pH-dependent properties, alongside the potential to be functionalized with targeting agents give them the unique property that can be used in targeted delivery systems for anticancer drugs. Also, due to the slow degradation of CaCO₃ matrices, these nanoparticles can be used as sustained release systems to retain drugs in cancer tissues for longer times after administration.

Areas covered: Development of drug delivery carriers using CaCO₃ nanoparticles has been reviewed. The current state of CaCO₃ nanoparticles as cancer drug delivery systems with focus on their special properties like pH-sensitivity and biodegradability has also been evaluated.

Expert opinion: According to our review, CaCO₃ nanoparticles, owing to their special characteristics, will have a potential role in safe and efficient cancer treatment in future.     

脂质立方液晶纳米粒作为药物载体的研究进展

由两亲性脂质分散在水性环境中自发形成各种几何形态构成的药物输送载体正成为制剂载药系统研究的热点之一。脂质立方液晶纳米粒是一定浓度的两亲性脂质分散在水溶液中自组装成含双连续水区和脂质区的闭合脂质双层“蜂窝状(海绵状)”结构,该独特的内部双水道结构和巨大膜表面积使其能够包封各种不同极性和剂量的药物,具有多样化的药物包裹性。作为药物载体,脂质立方液晶纳米粒还具有载药量大、保护多肽蛋白类药物和制备工艺简单等优点;可口服、局部黏膜和注射等多种途径给药,在多种剂型中有广泛的应用。本文对脂质立方液晶纳米给药系统的研究进行归纳和总结,并展望了脂质立方液晶纳米粒新型药物载体的应用前景。     

纳米粒给药系统逆转肿瘤多药耐药性的研究进展

多药耐药是导致肿瘤化疗失败的主要原因。对于大多数抗肿瘤药物,肿瘤细胞均会产生多药耐药现象, 但其耐药机制,目前没有统一的看法。本文对纳米粒给药系统逆转肿瘤多药耐药性进行了综述, 包括3种载药系统: 非修饰的、配体修饰的和多功能纳米粒给药系统,并对纳米粒给药系统逆转肿瘤多药耐药性的机制进行探讨。纳米粒通过拮抗和抵消肿瘤细胞主动外排药物的作用,提高肿瘤细胞内的药物浓度,同时减小对正常细胞的毒副作用, 逆转肿瘤的多药耐药性。这种新型的给药系统,结合了纳米技术及主动和被动靶向给药策略,在癌症治疗方面已显示出巨大的应用前景。       

以纳米颗粒为载体转染基因的发展概况

目的综述以纳米颗粒作为基因载体进行基因治疗的发展概况。方法依据国内外刊物公开发表的文献,对有关以纳米颗粒作为基因递送载体进行基因治疗的研究进行分类、归纳与整理。结果纳米颗粒转运系统能够保护被转运的基因,有较高的转染效率,具有良好的靶向性,并且提高了药物的生物利用度,显示出一定的缓控释作用。结论纳米颗粒作为基因递送载体具有广阔的发展前景。     

Long-circulating self-assembled cholesteryl albumin nanoparticles enhance tumor accumulation of hydrophobic anticancer drug

The objective of this study was to develop an albumin nanoparticle with improved stability and drug loading capacity. Generation of nanomaterials having physiologically stable and high potential for drug delivery is still challenging. Herein we synthesized cholesteryl albumin conjugate using N,N-disuccinimidyl carbonate coupling reagent and prepared paclitaxel-loaded cholesteryl albumin nanoparticle (PTX-Chol-BSA) by self-assembly with the mean hydrodynamic diameter of 147.6 ± 1.6 nm and with high loading capacity. PTX-Chol-BSA nanoparticle showed much higher colloidal stability than a simple complex of PTX and BSA (PTX–BSA) and sustained release profile. PTX-Chol-BSA nanoparticles exhibited greater cellular uptake and cytotoxicity in B16F10 and MCF-7 cancer cell lines, as compared with PTX in Cremophor EL/ethanol (PTX-Cre/EtOH) and PTX–BSA formulations. A pharmacokinetic study in tumor-bearing mice showed that the area under the concentration–time curve (AUC_{0–8 h}) following the administration of PTX-Chol-BSA was 1.6–2-fold higher than those following the administration of PTX-Cre/EtOH and PTX–BSA. In addition, the tumor AUC_{0–8 h} of PTX-Chol-BSA was around 2-fold higher than that of PTX–BSA. Furthermore, in vivo antitumor efficacy results revealed that PTX-Chol-BSA nanoparticles have greater antitumor efficacy. In conclusion, we demonstrated the potential of PTX-Chol-BSA nanoparticles for anti-tumor chemotherapy, with enhanced in vitro and in vivo behaviors, as compared to PTX–BSA and PTX-Cre/EtOH.     

Hierarchical pulmonary target nanoparticles via inhaled administration for anticancer drug delivery

Inhalation administration, compared with intravenous administration, significantly enhances chemotherapeutic drug exposure to the lung tissue and may increase the therapeutic effect for pulmonary anticancer. However, further identification of cancer cells after lung deposition of inhaled drugs is necessary to avoid side effects on normal lung tissue and to maximize drug efficacy. Moreover, as the action site of the major drug was intracellular organelles, drug target to the specific organelle is the final key for accurate drug delivery. Here, we designed a novel multifunctional nanoparticles (MNPs) for pulmonary antitumor and the material was well-designed for hierarchical target involved lung tissue target, cancer cell target, and mitochondrial target. The biodistribution in vivo determined by UHPLC–MS/MS method was employed to verify the drug concentration overwhelmingly increasing in lung tissue through inhaled administration compared with intravenous administration. Cellular uptake assay using A549 cells proved the efficient receptor-mediated cell endocytosis. Confocal laser scanning microscopy observation showed the location of MNPs in cells was mitochondria. All results confirmed the intelligent material can progressively play hierarchical target functions, which could induce more cell apoptosis related to mitochondrial damage. It provides a smart and efficient nanocarrier platform for hierarchical targeting of pulmonary anticancer drug. So far, this kind of material for pulmonary mitochondrial-target has not been seen in other reports.     

Mesoporous silica nanoparticles: synthesis,classification, drug loading,pharmacokinetics, biocompatibility,and application in drug delivery

Introduction: Mesoporous silica nanoparticles (MSNs) feature a high surface area and large pore volume, uniform and tunable pore size, and stable framework; thus, they have been used extensively as drug carriers.

Areas covered: The synthesis, classification, and the latest generation of MSNs, drug loading methods, modification of MSNs, pharmacokinetic studies, biocompatibility, and toxicity of MSNs, and their application in drug delivery systems (DDS) are covered in this review.

Expert opinion: It is crucial to uncover the mechanism for the formation of MSNs. Before drug loading, the characteristics of MSNs should be taken into consideration. In addition, the porosity, particle size and morphology, surface oxidation and surface functionalization can also influence the in vivo fate of MSNs, which is worthy of further study. Coating MSNs with novel materials may improve their biocompatibility, control the release of drugs loaded into the MSNs or enhance the uptake of the coated MSNs by tumor cells. MSNs can also be used as carriers for combination therapy in the treatment of cancer. Despite the rapid development of MSNs, the biological effects of these biomaterials remain relatively less understood.     

Advances in using chitosan-based nanoparticles for in vitro and in vivo drug and gene delivery

Importance of the field: This review aims to provide an overview of state-of-the-art chitosan-based nanosized carriers for the delivery of therapeutic agents. Chitosan nanocarriers are smart delivery systems owing to the possibility of their property alterations with various approaches, which would confer them with the possibility of spatiotemporal delivery features.

Areas covered in this review: The focus of this review is principally on those aspects that have not often been addressed in other reviews. These include the influence of physicochemical properties of chitosan on delivery mechanisms and chitosan modification with a variety of ligand moieties specific for cell surface receptors to increase recognition and uptake of nanocarriers into cells through receptor-mediated endocytosis. Multiple examples that demonstrate the advantages of chitosan-based nanocarriers over other delivery systems of therapeutic agents are highlighted. Particular emphasis is given to the alteration of material properties by functionalization or combination with other polymers for their specific applications. Finally, structural and experimental parameters influencing transfection efficiency of chitosan-based nanocarriers are presented for both in vitro and in vivo gene delivery.

What the reader will gain: The readers will acquire knowledge of parameters influencing the properties of the chitosan-based nanocarriers for delivery of therapeutic agents (genetic material or drugs) in vitro and in vivo. They will get a better idea of the strategies to be adapted to tune the characteristics of chitosan and chitosan derivatives for specific delivery applications.

Take home message: Chitosan is prone to chemical and physical modifications, and is very responsive to environmental stimuli such as temperature and pH. These features make chitosan a smart material with great potential for developing multifunctional nanocarrier systems to deliver large varieties of therapeutic agents administrated in multiple ways with reduced side effects.     

Solid lipid nanoparticles,an effective carrier for classical antifungal drugs

Solid-lipid nanoparticles (SLNs) are an innovative group of nanosystems used to deliver medicine to their respective targets with better efficiency and bioavailability in contrast to classical formulations. SLNs are less noxious, have fewer adverse effects, have more biocompatibility, and have easy biodegradability. Lipophilic, hydrophilic and hydrophobic drugs can be loaded into SLNs, to enhance their physical and chemical stability in critical environments. Certain antifungal agents used in different treatments are poorly soluble medications, biologicals, proteins etc. incorporated in SLNs to enhance their therapeutic outcome, increase their bioavailability and target specificity. SLNs-based antifungal agents are currently helpful against vicious drug-resistant fungal infections. This review covers the importance of SLNs in drug delivery of classical antifungal drugs, historical background, preparation, physicochemical characteristic, structure and sizes of SLNs, composition, drug entrapment efficacy, clinical evaluations and uses, challenges, antifungal drug resistance, strategies to overcome limitations, novel antifungal agents currently in clinical trials with special emphasis on fungal infections.     

载药纳米粒的脑内递药系统

介绍了载药纳米粒在脑内药物传递系统中的应用 ,提出了其脑靶向性可能的影响因素和机制