基于壳聚糖的纳米药物传递体系

壳聚糖作为天然高分子材料,不仅安全无毒、而且具有良好的生物相容性、可生物降解性等优点,在药物传递领域作为纳米载体倍受关注。壳聚糖基纳米载体材料制备条件简单温和,近年来,其相关研究也颇为新颖。本文以载体形成的驱动力作为切入点,从共价交联、离子相互作用、聚电解质络合物和疏水改性四个方面,总结不同种类壳聚糖基纳米载体的构筑方法,同时介绍该载体对药物传递中载药量、载药率、释放行为以及细胞毒性等方面的影响,在此基础上展望其未来的应用前景。     

Development strategies and biopharmaceutical aspects of drug delivery systems

One of the approaches to enhancing drug efficiency consists in the development of drug delivery systems. Development, research, and standardization of biologically available, functional, molecularly structured systems with unique mechanical, physicochemical, and other properties requires joint effort of many disciplines: from materials science to pharmacy. The main goal of the development of drug delivery systems is to prolong residence of a drug in biological fluids (this first of all relates to readily soluble pharmaceutical substances), ensure targeted action (especially with highly toxic substances), and enhance solubility for improving its bioavalability (with sparingly soluble substances).     

The effect of the molecular weight of chitosan nanoparticles and its application on drug delivery

Nanoparticulate drug delivery systems offer several advantages over conventional forms of dosing, with polymer nanoparticles prepared from biomaterials being good candidates for use in drug delivery. We selected fluorouracil (5FU) as a model drug because it has been suggested that chitosan might prevent the side effects induced by 5FU. We have exploited the complexation between oppositely charged macromolecules to develop a safe and efficient method of preparation of chitosan bead formulations for use as drug delivery systems. In this study, we examined the effect that the molecular weight of chitosan had on the resulting nanoparticles' properties; the initial concentration of chitosan was held constant, but its molecular weight was decreased through the action of NaNO₂. FTIR spectroscopy suggested that no structural change occurred during the depolymerization process. The diameters of the nanoparticles—determined using dynamic light scattering and TEM techniques—decreased as the value of the viscosity of molecular weight (Mv) of chitosan decreased. In addition, we prepared fluorouracil-loaded chitosan nanoparticles and characterized them using NMR spectroscopy. The encapsulation efficiency increased as the value of Mv of chitosan decreased. The particles produced using 55-kDa chitosan had a mean diameter of 70.6 nm and a 66% drug loading.     

O-羧甲基壳聚糖的制备及应用研究进展

O_羧甲基壳聚糖是壳聚糖的一种衍生物 ,具有比壳聚糖更优良的特性 ,有着更广阔的应用前景。本文对它的制备、性质、应用 ,特别是其在药物释放及基因治疗方面应用的研究进展进行了综述。     

Chitosan Nanoparticles-Insight into Properties,Functionalization and Applications in Drug Delivery and Theranostics

Nanotechnology-based development of drug delivery systems is an attractive area of research in formulation driven R&D laboratories that makes administration of new and complex drugs feasible. It plays a significant role in the design of novel dosage forms by attributing target specific drug delivery, controlled drug release, improved, patient friendly drug regimen and lower side effects. Polysaccharides, especially chitosan, occupy an important place and are widely used in nano drug delivery systems owing to their biocompatibility and biodegradability. This review focuses on chitosan nanoparticles and envisages to provide an insight into the chemistry, properties, drug release mechanisms, preparation techniques and the vast evolving landscape of diverse applications across disease categories leading to development of better therapeutics and superior clinical outcomes. It summarizes recent advancement in the development and utility of functionalized chitosan in anticancer therapeutics, cancer immunotherapy, theranostics and multistage delivery systems.     

天然糖类纳米药物传递系统的研究进展

纳米技术作为影响未来人类生活的世界三大新兴科技之一,其与药物传递系统的融合,既可以将药物的药理作用极大限度地发挥出来,又克服了药物本身的局限性.天然糖类的来源十分广泛,不仅价格低廉、无毒性,且具有良好的生物相容性和生物可降解性,被广泛用于纳米药物传递系统.本文对纳米药物传递系统的体系组成进行了归纳,重点阐述了常见糖类及...     

Perspectives of the development of pharmaceutical nanotechnology

The paper describes the principal lines of development of nanocarriers for medical substances, morphological groups of nanocarriers, and influence of the physical and chemical properties of matrix substances on the key stages of the technological process. Technology aspects of manufacturing nanocarriers, differences in the conditions and techniques for polymer and lipid drug delivery systems are presented in detail.     

Study on colon-specific 5-Fu pH-enzyme Di-dependent chitosan microspheres

Colon-specific drug delivery systems (CDDS) can improve the bioavailability of drug through the oral route. A novel formulation for oral administration using pH-enzyme Di-dependent chitosan mcirospheres (MS) and 5-Fu as a model drug has been investigated for colon-specific drug delivery by the emulsification/chemical cross-linking and coating technique, respectively. The influence of polymer concentration, ratio of drug to polymer, the amount of crosslinking agent and the stirring speed on the encapsulation efficiency, particle size in microspheres were evaluated. The best formulation was optimized by an orthogonal design. Drug release studies under conditions mimicking stomach to colon transit have shown that the drug was protected from being released in the physiological environment of the stomach and small intestine. The plasma concentrations of 5-Fu after oral administration of coated chitosan MS to rats were determined and compared with that of 5-Fu solution. The in vivo pharmacokinetics study of 5-Fu loaded pH-enzyme Di-dependent chitosan MS showed sustained plasma 5-Fu concentration-time profile. The in vitro release correlated well with the pharmacokinetics profile. The results clearly demonstrated that the pH-enzyme Di-dependent chitosan MS is potential system for colon-specific drug delivery of 5-Fu.     

Biodegradable starburst carbon chain polymer-protein and lysine dendrite conjugates: adjustment of immune properties,DNA bonding and delivery

In the past decade, the development of gene therapy technology has focused on the design of new nonviral carriers for gene delivery. Proteins modified with polyethyleneimine^[1] or polylysine^[2] as well as dendrites^[3] have shown to be perspective carriers for DNA targeted delivery. The usage of protein conjugates as carriers of biologically active compounds will depend on the adjustment of their immune properties. To investigate this we have prepared starburst carbon chain polymer/protein conjugates containing low molecular weight biologically active compounds, salsolinol and bradykinin, in the polymer moieties and studied their immune properties. We have shown that chemical structure of the polymer moiety determines the conjugate biodegradation as well as their immune properties. The starburst poly(N-vinylimidazole) transferring poly(N-vinylimidazole) and polylysine 3G lysine dendrite conjugates have been prepared. The study of their ability to bind DNA and to guarantee its targeted delivery have shown that they are perspective DNA carriers.     

Innovational combination of hetero-bifunctional N-PEG quinoline scaffolds derivatives with improved anticancer activity against breast and colon cancer cell lines and P-glycoprotein,cytochrome p450 enzyme activity prediction

Polyethylene glycol (PEG) is a polymer that is widely used as a carrier for drug delivery systems (DDS). A library of N-PEGylated quinoline derivatives of PEG molecular weight 200 was prepared rapidly after the activation of PEGs using maleic anhydride. Quinoline with a polymer backbone is essential as new material. PEG is a water-soluble nonionic polymer approved by food and drug organizations for medicine applications. Because of its nontoxic grapheme, it is widely utilized in numerous biochemical, cosmetic, pharmaceutical, and industrialized applications. The modern SwissADME is a web tool that stretches free admittance to a pool of hasty, yet solid, clarifying models for physicochemical properties, pharmacokinetics, and therapeutic science. The present facile synthetic strategy can be a practical approach for incorporating polymeric carriers conjugated with drug moieties, either in the backbone of the polymer or as a terminal and pendant group on the polymer chains.     

壳聚糖及其衍生物作为疫苗佐剂的研究进展

疫苗佐剂能够增强机体对抗原的免疫应答反应或改变免疫应答反应类型,延长疫苗在体内作用时间,提高疫苗效力。壳聚糖能有效地将疫苗递送到靶抗原递呈细胞或组织,激活抗原提呈细胞,诱导产生免疫应答,促进Th1/Th2应答反应的平衡,因此,壳聚糖作为疫苗佐剂具有一定的潜力。为了解决壳聚糖在中性和碱性溶液中溶解性差,以及进一步提高其黏膜黏附性和靶向性等问题,通过对壳聚糖进行化学改性,生成一系列壳聚糖衍生物,提高其佐剂性能。本论文就近年来有关壳聚糖及其衍生物作为疫苗佐剂和递送系统在疫苗中的应用进行了综述,总结并提出了壳聚糖及其衍生物在疫苗佐剂应用领域所面临的问题以及其未来的发展方向,使读者对其有全面的了解。     

Protective,Biostimulating, and Eliciting Effects of Chitosan and Its Derivatives on Crop Plants

Chitosan is a biodegradable and biocompatible polysaccharide obtained by partial deacetylation of chitin. This polymer has been gaining increasing popularity due to its natural origin, favorable physicochemical properties, and multidirectional bioactivity. In agriculture, the greatest hopes are raised by the possibility of using chitosan as a biostimulant, a plant protection product, an elicitor, or an agent to increase the storage stability of plant raw materials. The most important properties of chitosan include induction of plant defense mechanisms and regulation of metabolic processes. Additionally, it has antifungal, antibacterial, antiviral, and antioxidant activity. The effectiveness of chitosan interactions is determined by its origin, deacetylation degree and acetylation pattern, molecular weight, type of chemical modifications, pH, concentration, and solubility. There is a need to conduct research on alternative sources of chitosan, extraction methods, optimization of physicochemical properties, and commercial implementation of scientific progress outcomes in this field. Moreover, studies are necessary to assess the bioactivity and toxicity of chitosan nanoparticles and chitosan conjugates with other substances and to evaluate the consequences of the large-scale use thereof. This review presents the unique properties of chitosan and its derivatives that have the greatest importance for plant production and yield quality as well as the benefits and limitations of their application.     

Chitosan nanoparticles: a promising system in novel drug delivery

The ability of nanoparticles to manipulate the molecules and their structures has revolutionized the conventional drug delivery system. The chitosan nanoparticles, because of their biodegradability, biocompatibility, better stability, low toxicity, simple and mild preparation methods, offer a valuable tool to novel drug delivery systems in the present scenario. Besides ionotropic gelation method, other methods such as microemulsion method, emulsification solvent diffusion method, polyelectrolyte complex method, emulsification cross-linking method, complex coacervation method and solvent evaporation method are also in use. The chitosan nanoparticles have also been reported to have key applications in parentral drug delivery, per-oral administration of drugs, in non-viral gene delivery, in vaccine delivery, in ocular drug delivery, in electrodeposition, in brain targeting drug delivery, in stability improvement, in mucosal drug delivery in controlled drug delivery of drugs, in tissue engineering and in the effective delivery of insulin. The present review describes origin and properties of chitosan and its nanoparticles along with the different methods of its preparation and the various areas of novel drug delivery where it has got its application.     

壳聚糖及其衍生物基因载体的研究进展

壳聚糖是一种天然的生物可降解性,生物相容性好而且安全无毒的多糖,因而它成为基因治疗载体研究的热点。本文就近年来壳聚糖及其衍生物作为基因载体转染的研究进展和现状作简要的综述,并对转染率的影响因素如壳聚糖的分子量、粒径、脱乙酰度等进行着重介绍。     

Ultrasonically controlled polymeric drug delivery

The area of polymeric controlled drug delivery systems has been a field of increasing interest. However, relatively little attention has been given to developing systems in which the rate of delivery can be manipulated externally. We now report that release rates of biologically active substances from a polymeric matrix can be repeatedly modulated from a position external to the environment of use by ultrasonic energy. The ultrasound affects the degradation rate of bioerodible polymers as well as permeation through non-erodible polymers. The system has been shown to be responsive in vivo. Skin histopathology of the ultrasound treated area didn't reveal any differences between the treated skin and the untreated controls.     

Investigation of innovative synthesis of biologically active compounds on the basis of newly developed reactions

Synthesis of biologically active compounds, including natural products and pharmaceutical agents, is an important and interesting research area since the large structural diversity and complexity of bioactive compounds make them an important source of leads and scaffolds in drug discovery and development. Many structurally and also biologically interesting compounds, including marine natural products, have been isolated from nature and have also been prepared on the basis of a computational design for the purpose of developing medicinal chemistry. In order to obtain a wide variety of derivatives of biologically active compounds from the viewpoint of medicinal chemistry, it is essential to establish efficient synthetic procedures for desired targets. Newly developed reactions should also be used for efficient synthesis of desired compounds. Thus, recent progress in the synthesis of biologically active compounds by focusing on the development of new reactions is summarized in this review article.     

Free-radical cross-linking of serum albumin molecules on the surface of magnetite nanoparticles in aqueous dispersion

A novel universal approach to cross-linking of protein macromolecules on the surface of magnetite nanoparticles has been developed. The approach is based on protein liability to free-radical modification, leading to the formation of intermolecular covalent cross-links. Free radicals are locally generated on the surface of nanoparticles. Stable coatings of serum albumin 3 nm thick are formed on the surface of magnetite nanoparticles. Using a set of physicochemical methods, it has been proven that stable coatings composed of protein macromolecules are formed around individual nanoparticles. The presence of reactive groups in the protein structure makes it possible to perform subsequent modification of the surface layers-in particular, to graft nonprotein drugs. The approach developed can be used to create superfine systems with desired surface properties for targeted delivery of drugs and biologically active substances.     

Preparation, characterization and in vitro dissolution studies of solid systems of valdecoxib with chitosan

In the present study, the solubilizing and amorphizing properties of Valdecoxib (a poorly water soluble anti inflammatory drug) with low molecular weight chitosan (a polymer), have been investigated. Binary systems of varying drug/polymer ratios were prepared using different techniques (physical mixing, co-grinding, kneading) and were tested for dissolution. Drug carrier interactions were investigated in both the liquid and solid state, by phase solubility analysis, differential scanning calorimetry, powder X-ray diffractrometry, FT-IR spectroscopy and scanning electron microscopy. The solubility of the drug increased with increasing polymer concentration showing A(N) type phase solubility diagram. Differential scanning calorimetry, powder X-ray diffractrometry and scanning electron microscopic studies of binary systems suggested generation of amorphous form of drug (in kneading and co ground mixtures). IR spectroscopy revealed the presence of hydrogen bonding in kneading and co ground mixtures. Drug dissolution was improved with increasing the polymer concentration in the mixture (Kneaded>co ground>physical mixture), which was attributed to the amorphonization and/or decreased drug crystallinity, size and polymer wetting effect. Enhanced dissolution combined with its direct compression feasibility and anti ulcerogenic action results in low molecular weight chitosan for developing fast release oral solid dosage forms of valdecoxib.     

Chitosan based hybrid hydrogels for drug delivery: Preparation,biodegradation, thermal,and mechanical properties

In the present paper, biodegradable hybrid hydrogels were prepared by using chitosan as a natural polymer and polyurethane containing azomethine as a synthetic polymer for the drug delivery application for 5-fluorouracil. The fabricated hydrogels were characterized via FT-IR and SEM analysis. Besides, the thermal, mechanical, and wettability properties, water uptake, biodegradation, protein absorption, drug loading, and release behaviors of the hybrid hydrogels were studied. The obtained results indicated that the fabricated hybrid hydrogels have exhibited good mechanical, hydrophilic, water uptake, and biodegradation behaviors. The hybrid hydrogels also showed 50% drug release amounts and they could be a good candidate for the controlled delivery of 5-FU due to these properties.     

壳聚糖/乙酰半胱氨酸纳米粒子的性质及体外释药性

制备了一种基于壳聚糖/乙酰半胱氨酸偶合物(CS-NAC)的新型巯基纳米粒子并进行了结构表征, 同时对纳米粒子的黏附性、溶胀性和药物释放进行了测试. 结果表明, 纳米粒子具有较小的粒径(140~210 nm)和正的表面电位(19.5~31.7 mV), 胰岛素的载药量达到13%~42%. 这些性质随着巯基含量的变化而变化. 与壳聚糖纳米粒子相比, 巯基壳聚糖纳米粒子表现出了更强更快的黏附性质. 体外释放研究结果表明, 巯基壳聚糖纳米粒子的胰岛素释放具有pH响应性. 在pH=6.8时, 15 min即能释放58.6 %的胰岛素; 而在pH=5.4时, 24 h内仅有不到40%的胰岛素被释放. 因此, CS-NAC纳米粒子用于胰岛素的黏膜给药体系具有很好的应用前景.