单分散磁性纳米粒子靶向药物载体

本文综述了单分散磁性氧化铁纳米粒子的主要制备方法、表面修饰以及在生物医学靶向药物方面的应用研究进展。金属有机前驱体高温热分解法、溶剂热合成法和LSS（liquid-solid-solution）法是目前制备高质量单分散磁性纳米粒子比较有效的手段。通过表面修饰制备出的具有良好水溶性、生物相容性和活性功能基团的磁靶向药物载体将可能实现定位蓄积、高效载药、控制释药和可生物降解等靶向治疗癌症的目的。开发出具有荧光检测、主动靶向识别、高效载药、智能控药释放、无毒副作用和生物相容性于一体的多功能靶向药物载体将是其发展趋势。     

Creation and application of psychoactive designer drugs data library using liquid chromatography with photodiode array spectrophotometry detector and gas chromatography-mass spectrometry

In order to quickly confirm a potentially hazardous psychoactive designer drug (a compound in which part of the molecular structure of a stimulant or narcotic has been modified), we created a psychoactive drugs data library by performing analysis using liquid chromatography with photodiode array spectrophotometry (LC/PDA) and gas chromatography-mass spectrometry (GC/MS). The data in this library consist of the LC capacity factor (k′) ratios in relation to the internal standard, the ultraviolet (UV) spectra and the MS spectra of 104 compounds. By performing a comparative study of the data in this report with the analytical data for commercial and illegal drug products, it is possible to quickly identify the psychoactive designer drugs in 205 purchased products by using the library. Further, it is possible to analogize the structure of drugs for which there is no matching data in the library using similar data.Furthermore, when structural isomers of controlled substances have detected from the presented library, similarity of their biological effects on human will be predicted, thus leading to regulate their public circulation. Examples of these types of isomers include, for instance, the narcotic 3,4,5-trimethoxyamphetamine (TMA) and its positional isomers 2,4,5-trimethoxyamphetamine (TMA-2) and 2,4,6-trimethoxyamphetamine (TMA-6), or the narcotic 1-(3-chlorophenyl)piperazine (3CPP) and its isomers 1-(o-chlorophenyl)piperazine (2CPP) and 1-(p-chlorophenyl)piperazine (4CPP). Differentiation of these compounds is necessary in regulating them, and we report here the results of a study of a method to confirm these compounds using the present library.     

Screen anticancer drug in vitro using resonance light scattering technique

An in vitro screening model using resonance light scattering (RLS) technique with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) reagent as the reactive probe to target cancer cell was firstly developed. In this model, MTT was reduced by viable cancer cells to produce a purple formazan. Cell viability was proportional to the number of formazan induced strong light scattering signal. The inhibition rate of anticancer drug was found to vary inversely with the H₂₂-MTT system RLS intensity. So it was intuitive to see the sequence of the tumor suppressive activity of six anticancer drugs without data processing by RLS/MTT screening spectra. Compared with the traditional MTT method, this method has high sensitivity, low detection limit and quite intuitive screening results which were identical to those obtained from the MTT colorimetric assay.     

Peptidomimetics and metalloprotease inhibitors as anticancer drugs

Peptidomimetics with three types, as the structural or functional mimetics of natural active peptides, can preserve the bioactivity and improve the bioavailability and the specificity towards the targets of the lead peptides. Peptidomimetics of high bioactivity can be designed through various ways including conformation restriction, modification and non-peptide design. Recently the concentration on the development of cancer chemotherapeutic drugs was transferred from cytotoxic drugs to target-based drugs, and many proteases and peptidases that play key roles in the process of tumor genesis and development was discovered, which means that peptidomimetics as potential cancer chemotherapeutic drugs should be paid close attention to. Our laboratory has focused on the development of small-molecule peptidomimetic inhibitors of APN, MMPs and HDACs as target-based anticancer agents. These three zinc-dependent metalloproteinases play very important roles in the process of tumor genesis, invasion, metastasis, angiogenesis and matrix degradation, so small-molecule peptidomimetic inhibitors based on them would be quite potential in the development of chemotherapeutic drugs with high selectivity. Supported by the National High Technology Research and Development Program of China (863 Project) (Grant No. 2007AA02Z314), the National Natural Science Foundation of China (Grant Nos. 90713041 & 30772654), and the Doctoral Fund of Ministry of Education of China (Grant No. 20060422029)     

Review on supermolecules as chemical drugs

Supramolecular medicinal chemistry field has been a quite rapidly developing, increasingly active and newly rising interdiscipline which is the new expansion of supramolecular chemistry in pharmaceutical sciences, and is gradually becoming a relatively independent scientific area. Supramolecular drugs could be defined as medicinal supermolecules formed by two or more molecules through non-covalent bonds. So far a lot of supermolecules as chemical drugs have been widely used in clinics. Supermolecules as chemical drugs, i.e. supramolecular chemical drugs or supramolecular drugs, which might have the excellences of lower cost, shorter period, higher potential as clinical drugs for their successful research and development, may possess higher bioavailability, better biocompatibility and drug-targeting, fewer multidrug-resistances, lower toxicity, less adverse effect, and better curative effects as well as safety, and therefore exhibit wide potential application. These overwhelming advantages have drawn enormous special attention. This paper gives the definition of supramolecular drugs, proposes the concept of supramolecular chemical drugs, and systematically reviews the recent advances in the research and development of supermolecules, including organic and inorganic complex ones as chemical drugs in the area of antitumor, anti-inflammatory, analgesic, antimalarial, antibacterial, antifungal, antivirus, anti-epileptic, cardiovascular agents and magnetic resonance imaging agents and so on. The perspectives of the foreseeable future and potential application of supramolecules as chemical drugs are also presented. Supported by the Southwest University (Grant Nos. SWUB2006018 & XSGX0602), the Natural Science Foundation of Chongqing (Grant Nos. 2007BB5369 & 2006BB4341) and the Key Project from the Personnel Department of China (Grant No. 2002-99)     

Polymers for targeted and/or sustained drug delivery

Recent advances in the use of polymers for passive targeting of drugs attached or incorporated into polymeric species (enhanced permeability and retention, EPR) as well as active targeting of drugs by ligands or antibodies of receptors overexpressed on the surface of the targeted cells, is discussed in the present review. Examples of sustained, slow release of a drug incorporated into a polymeric matrix are cited. Drugs used for passive modes of targeting have been described in the context of polymer‐drug conjugates, drugs in the polymer coated liposomes, and drugs inserted into polymeric micelles. Active targeting of the drugs and their internalization by receptors, on the surface of the targeted cells, was also discussed. Release of the drugs inside cells, after are broken the environmentally sensitive links attaching them to polymeric platforms was described. Examples illustrate targeting drug by local heat generated by ultrasound, or by photodynamic treatment. Delivery modes of drugs incorporated into other nanoparticles and the concept of prodrugs have been investigated. Copyright © 2008 John Wiley & Sons, Ltd.     

Mass defect filter technique and its applications to drug metabolite identification by high‐resolution mass spectrometry

Identification of drug metabolites by liquid chromatography/mass spectrometry (LC/MS) involves metabolite detection in biological matrixes and structural characterization based on product ion spectra. Traditionally, metabolite detection is accomplished primarily on the basis of predicted molecular masses or fragmentation patterns of metabolites using triple‐quadrupole and ion trap mass spectrometers. Recently, a novel mass defect filter (MDF) technique has been developed, which enables high‐resolution mass spectrometers to be utilized for detecting both predicted and unexpected drug metabolites based on narrow, well‐defined mass defect ranges for these metabolites. This is a new approach that is completely different from, but complementary to, traditional molecular mass‐ or MS/MS fragmentation‐based LC/MS approaches. This article reviews the mass defect patterns of various classes of drug metabolites and the basic principles of the MDF approach. Examples are given on the applications of the MDF technique to the detection of stable and chemically reactive metabolites in vitro and in vivo. Advantages, limitations, and future applications are also discussed on MDF and its combinations with other data mining techniques for the detection and identification of drug metabolites. Copyright © 2009 John Wiley & Sons, Ltd.     

Fabrication of an ��-lipoic acid-eluting poly-(D,L-lactide-co-caprolactone) cuff for the inhibition of neointimal formation

The purpose of this study was to develop a novel polymer cuff for the local delivery of α-lipoic acid (ALA) to inhibit neointimal formation in vivo. The polymer cuff was fabricated by incorporating the ALA into poly-(_D,L-lactide-co-caprolactone) 40:60 (PLC), with or without methoxy polyethylene glycol (MethoxyPEG). The release kinetics of ALA and in vitro degradation by hydrolysis were analyzed by HPLC and field emission scanning electron microscopy (FE-SEM), respectively. In vivo evaluation of the effect of the ALA-containing polymer cuff was carried out using a rat femoral artery cuff injury model. At 24 h, 48% or 87% of the ALA was released from PCL cuffs with or without MethoxyPEG. FE-SEM results indicated that ALA was blended homogenously in the PLC with MethoxyPEG, whereas ALA was distributed on the surface of the PLC cuff without MethoxyPEG. The PLC cuff with MethoxyPEG showed prolonged and controlled release of ALA in PBS, in contrast to the PLC cuff without MethoxyPEG. Both ALA-containing polymer cuffs had a significant effect on the inhibition of neointimal formation in rat femoral artery. Novel ALA-containing polymer cuffs made of PLC were found to be biocompatible and effective in inhibiting neointimal formation in vivo. Polymer cuffs containing MethoxyPEG allowed the release of ALA for one additional week, and the rate of drug release from the PLC could be controlled by changing the composition of the polymer. These findings demonstrate that polymer cuffs may be an easy tool for the evaluation of anti-restenotic agents in animal models.     

Polymer complexes: XLIX—Supramolecular modeling of bonding in novel rare earth polymeric rhodanine drug complexes

Novel supramolecular rare earth polymeric hydrazone complexes of 5-sulphadiazineazo-3-phenyl-2-thiaxo-4-thiazolidinone (HL) of the composition [(Ln)₂(HL)₃(NO₃)₆]_n (where Ln = La(1), Y(2), Pr(3), Nd(4), Sm(5), Gd(6) and Ho(7)) have been prepared and characterized on the basis of their chemical analyses, magnetic measurements, conductance, visible and IR spectral data. Composition, conductance and IR spectral data of complexes show that all these act as a tetradentate ligand. Electronic spectra indicate weak covalent character in the metal–ligand bond. The spectra of Nd³⁺ and Ho³⁺ show characteristic f–f transitions and the metal–ligand covalency in % has been evaluated. The spectral properties of the above polymeric complexes are also discussed.     

Charge‐Conversional Polyionic Complex Micelles—Efficient Nanocarriers for Protein Delivery into Cytoplasm

Special delivery! Polyionic complex (PIC) micelles that contain the charge‐conversional moieties citaconic amide or cis‐aconitic amide were developed for cytoplasmic protein delivery. The increase of the charge density on the protein cargo helped the stability of the PIC micelles without cross‐linking, and the charge‐conversion in endosomes induced the dissociation of the PIC micelles to result in efficient endosomal release (see picture).