壳聚糖及其衍生物在促进药物口服吸收中的应用

目的 介绍壳聚糖及其衍生物在促进药物口服吸收中的应用。方法 以国内外发表的文献为依据．总结归纳了壳聚糖及其衍生物促进药物口服吸收中的机理及影响因素。结果与结论 壳聚糖及其衍生物能较好地促进药物的口服吸收。     

壳聚糖衍生物及其胶束：特性、功能化修饰和在药物传递系统中的应用

壳聚糖是一种天然多糖,具有无毒、可生物降解、生物相容性等诸多优点,但水溶性差的自身特点限制了其在药剂学中的应用,而其经合理的结构设计、修饰和优化,可获得性能良好的两亲性壳聚糖衍生物,这些衍生物在水溶液中能自组装成具有良好药物传输性能（如载药量、稳定性、刺激敏感性、靶向性等）的胶束,并被广泛应用于构建药物传递系统,以改善药物的溶解性、靶向性、生物利用度及耐药性．降低药物的毒副作用。综述壳聚糖衍生物结构对其胶束药物传输性能的影响以及壳聚糖衍生物及其胶束的功能化修饰和在药物传递系统中的应用。     

海藻酸钠及其衍生物在生物医药中的应用进展

目的:总结海藻酸钠及其衍生物在生物医药中的应用进展,为其临床应用与开发提供参考。方法:以"海藻酸钠""衍生物""组织工程""介入治疗""缓释""靶向""载体""Alginate""Derivative""Tissue engineering""Intervention""Control release""Target""Delivery"等为关键词,组合查询1990年1月-2019年4月在中国知网、维普网、ScienceDirect、PubMed等数据库中的相关文献,归纳海藻酸钠衍生物的种类,并从药物递送、创面修复、组织工程、介入治疗等4个方面总结海藻酸钠及其衍生物在生物医药中的应用进展。结果与结论:共检索到相关文献13 387篇,其中有效文献63篇。海藻酸钠衍生物包括基团衍生物(乙酰化衍生物、磷酸化衍生物、硫酸化衍生物)和接枝共聚物。在药物递送方面,海藻酸钠及其衍生物可作为缓控释药物载体、生物大分子载体、靶向给药载体递送药物;在创面修复方面,海藻酸钠及其衍生物可被开发为各类医用敷料,达到止血、抗菌、促进创面愈合等效果;在组织工程方面,海藻酸钠及其衍生物可作为细胞微囊化载体或支架材料,为细胞提供生长支撑的同时还可递送生物活性分子,在软骨、硬骨、皮肤组织修复方面应用广泛;在介入治疗方面,海藻酸钠及其衍生物可将血管栓塞介入治疗和靶向药物治疗相结合,实现药物局部富集,增强疗效。临床上海藻酸钠通常被制成水凝胶进行应用,但存在机械强度差、对疏水性分子负载量低、降解不易控制等缺点,通过乙酰化、磷酸化、硫酸化等形成相应的衍生物可扩大其应用范围,但海藻酸钠及其衍生物的应用仍然存在一些问题,如其力学性能和生物相容性还有待提高、产生的细胞毒性仍需降低,因此,在后续研究中还需深入挖掘海藻酸钠及其衍生物的应用潜能和安全性,为其临床应用提供依据。     

毛细管电色谱的研究进展及其在药物分析中的应用

目的：毛细管电色谱在药物分析中的应用研究。方法：结合国内外有关毛细管电色谱的文献资料,综述毛细管电色谱的研究进展、毛细管电色谱整体柱制备新进展及其在药物分析中的应用。结果：毛细管点色谱在分析领域已得到广泛良好的应用。结论：毛细管电色谱拥有广阔的应用前景。     

多糖及其衍生物在药物传递系统中的应用研究新进展

多糖是一类生物相容性好、无毒、非免疫原性的生物材料,现已广泛应用于药物传递系统。综述海藻酸盐、几丁质、葡聚糖、透明质酸和肝素等多糖及其衍生物的理化和生物学特性以及在药物传递系统中的应用进展。     

环糊精及其衍生物在药物分析中的应用

鉴于环糊精及其衍生物在药学领域应用的潜力很大，本文综述其在药物分析中的应用，重点介绍在各类型色谱分析方面的应用进展。     

液相色谱技术在体内药物分析中的应用

现代药学的迅速发展促进针对药物及其代谢物在机体内处置过程的研究不断深入 ,一方面对体内药物分析研究方法和手段提出了越来越高的要求 ,另一方面也推动了体内药物分析研究方法的蓬勃发展。近年来 ,色谱技术特别是液相色谱技术不断发展和完善 ,在灵敏度和选择性等方面都有了很大提高 ,使得对复杂生物样品中药物及其代谢物的测定变得更加准确、快速和简便 ,本文就近年来新型液相色谱技术在体内药物分析中的应用作一简要综述。1　胶束色谱法 (ｍｉｃｅｌｌａｒｃｈｒｏｍａｔｏｇｒａｐｈｙ ,ＭＣ)ＭＣ是一种在常规色谱柱上实现体液样品直接…     

两亲性壳聚糖衍生物在药物递送中的研究进展

壳聚糖是一种来源丰富的碱性多糖,具有良好的生物相容性和生物可降解性,但是其差的溶解性限制了壳聚糖在医药领域的应用。为了提高壳聚糖的溶解性,研究者对壳聚糖进行两亲性改性,通过选择不同的亲水、疏水基团,设计合成了两亲性壳聚糖衍生物。并利用其在水溶液中的自组装性能,形成两亲性壳聚糖纳米粒,用于多种药物的递送,以达到增加药物溶解性、稳定性、降低药物毒性和提高生物利用度等目的。本文综述了两亲性壳聚糖衍生物的合成方法,以及其在药物递送系统中的应用。     

体内药物分析中色谱技术的应用

本文综述了国内外用于体内药物分析的一些新兴色谱技术,如超临界流体色谱法、毛细管电泳法、手性色谱法、胶束色谱法、分子生物色谱法、色谱固相微萃取联用法、色谱-质谱联用法、色谱-色谱联用法等的具体应用进展;展望了色谱技术在体内药物分析应用中的前景及其发展方向,即开发新的检测技术及借助计算机手段,以实现其连续化、自动化、联用化及智能化。     

色谱新技术在体内药物分析中的应用

综述了国内外用于体内药物分析的一些新兴色谱技术,如色谱-固相微萃取联用法、色谱-质谱联用法、色谱-色谱联用法、超临界流体色谱法、毛细管电泳法、分子生物色谱法、手性色谱法等的具体应用进展;展望了色谱技术在体内药物分析应用中的前景及其发展方向,即开发新的检测技术及借助计算机手段,以实现其连续化、自动化、联用化及智能化.     

Simultaneous interaction of steroidal drugs with gamma- and hydroxypropyl-beta-cyclodextrin studied by charge-transfer chromatography

The simultaneous interaction of 15 steroidal drugs with tau-cyclodextrin (tauCD) and hydroxypropyl-beta-CD (HPbetaCD) was determined by charge transfer chromatography and the relative strength of interaction was calculated for each drug-tauCD-HPbetaCD ternary complex. The mixture of CDs interacted with each steroidal drugs decreasing the lipophilicity of the guest molecules. The chemical structure of steroidal drugs markedly influenced their capacity to interact with the mixture of CDs, the more lipophilic compounds formed stronger complexes with CDs. In the overwhelming majority of cases the stability of drug-tauCD-HPbetaCD system was higher than those of binary (drug-tauCD and drug-HPbetaCD) system indicating the probability of ternary complex formation. The data indicated that the ternary complex formation has to be taken into consideration in pharmaceutical formulations containing more than one type of CD or CD derivatives.     

Cyclodextrins: structure,physicochemical properties and pharmaceutical applications

Since their discovery over 100 years ago cyclodextrins (CDs) have been the subject of numerous scientific publications. In 2016 alone CDs were the subject of over 2200 research articles published in peer-reviewed journals and mentioned in over 2300 patents and patent applications, many of which were on pharmaceutical applications. Natural CDs and their derivatives are used as enabling pharmaceutical excipients that enhance aqueous solubility of poorly soluble drugs, increase drug permeability through biological membranes and improve drug bioavailability. Unlike conventional penetration enhancers, their hydrophilic structure and high molecular weight prevents them from penetrate into lipophilic membranes leaving biological membranes intact. The natural CDs and some of their derivatives have monographs in pharmacopeias and are also commonly used as food additives and in toiletry products. CDs form inclusion complexes with lipophilic moieties of hydrophobic drugs. Furthermore, CDs are able to form non-inclusion complexes and self-assembled aggregates; small and large complex aggregates with micellar-like structures that can enhance drug solubility. Excipients commonly used in pharmaceutical formulations may have additive or inhibiting effect on the CD solubilization. Here various methods used to investigate CD aggregate formation are reviewed as well as techniques that are used to increase the solubilizing effects of CDs; methods that enhance the apparent intrinsic solubility of drugs and/or the complexation efficacy and decrease the amount of CD needed to develop CD-containing pharmaceutical formulations. It will be explained how too much or too little CD can hamper drug bioavailability, and the role of CDs in solid dosage forms and parenteral formulations, and examples given on how CDs can enhance drug delivery after ocular, nasal and pulmonary administration.     

Cyclodextrins in peptide and protein delivery

The objective of this contribution is to summarize recent findings on the potential of cyclodextrins (CDs) and their derivatives as carriers for therapeutically important peptides, proteins and oligonucleotides. As one of the indices relevant to bioadaptability of CDs in pharmaceutical uses, their interaction with cellular membranes in vitro is outlined. CDs enable the creation of advanced dosage forms for the next generation of drugs that are difficult to formulate and deliver with the existing pharmaceutical excipients. Furthermore, the diagnostic uses of CDs for the direct measurement of cholesterol in high-density and low-density lipoproteins in serum are discussed on the basis of their ability to recognize the surface properties of each lipoprotein particle.     

Interactions in solution between cyclodextrins and statins

Cyclodextrins (CDs) are cyclic oligosaccharides, capable of forming inclusion complexes with hydrophobic molecules in aqueous solution and therefore, of improving the bioavailability of many drugs. They are biocompatible with living cells and do not cause toxic side effects. In this study, interactions in aqueous solutions between chemically different CDs and lovastatin and simvastatin, respectively, were investigated. It was found that the solubility of both statins can be considerably increased by the CD derivatives. The influence of the chemical structure of CD and of the temperature and pH on the solubility of the statin derivatives is described. Possible ways of increasing the solubility of these cholesterol-lowering drugs and their utilization in practice are also outlined.     

环糊精及其衍生物在手性药物分离分析中的应用

有近一半的药物具有手性但通常两种异构体并不具有相同的药理活性,有一些异构体甚至具有毒性,因此,采用将手性药物良好分离的分析方法进行质控对药品的质量控制具有重要意义。环糊精及其衍生物是手性药物分离分析中常用的手性添加剂和手性固定相,本文对近年来环糊精及其衍生物在高效液相、气相、毛细管电泳、质谱、超临界流体等方面的应用进行综述。     

Separation of vinca alkaloid enantiomers by capillary electrophoresis applying cyclodextrin derivatives and characterization of cyclodextrin complexes by nuclear magnetic resonance spectroscopy

In this work, the enantiomeric separation of three vinca alkaloid enantiomers (vincamine, vinpocetine and vincadifformine) has been investigated in an aqueous capillary electrophoresis (CE) system using cyclodextrins (CDs). The investigated CDs were the native α-, β-, and γ-CDs and their hydroxypropylated, randomly methylated, carboxymethylated and sulfobutylated derivatives. The first part of this study consisted of the determination of the apparent averaged complex stability constants with the selected CDs. Several parameters, such as the nature and the concentration of the CD, were studied and were found to have a significant effect on the enantiomeric resolution for all studied compounds. All three vinca alkaloids were successfully enantioseparated with CDs where different migration orders were observed in case of several CDs depending on the cavity size or substituent of the host. Chiral separation and determination of the stability constants were also performed with NMR spectroscopy which confirmed the CE results. Averaged stoichiometries of the complexes were determined using the Job plot method resulting in a 1:1 complex irrespective of the alkaloid enantiomers or cyclodextrin derivative. The structures of the inclusion complexes were elucidated using 2D ROESY NMR spectroscopy. On the basis of NMR results reversal of enantiomer migration order was clarified in various cases.     

Cyclodextrin complexes: Perspective from drug delivery and formulation

Cyclodextrins (CDs) have been widely investigated as a unique pharmaceutical excipient for past few decades and is still explored for new applications. They are highly versatile oligosaccharides which possess multifunctional characteristics, and are mainly used to improve the physicochemical stability, solubility, dissolution rate, and bioavailability of drugs. Stability constant, factors affecting complexation, techniques to enhance complexation efficiency, the preparation methods for molecular inclusion complexes and release of guest molecules are discussed in brief. In addition, different CD derivatives and their pharmacokinetics are elaborated. Further, the significance of CD complex in aqueous solubility, dissolution and bioavailability, stability, and taste masking is explained. The recent advancement of CDs in developing various drug delivery systems is enlightened. Indeed, the potential of CDs by means of inclusion complex formation have widen the applicability of these materials in various drug delivery systems including ocular, osmotic, mucoadhesive, transdermal, nasal, and targeted delivery systems. Feasibility studies have been performed on the benefit of these cyclic oligomers as nanocarriers, a strategy that can modify the drugs with improved physicochemical properties. Studies also demonstrated the feasibility of CDs to self‐assemble in the form of stable nanoaggregates, which may extend the scope of CDs in drug delivery to the continually expanding list of new drug entities.     

Cytotoxic examinations of various cyclodextrin derivatives on Caco-2 cells

Cyclodextrins (CDs) are widely used compounds in pharmaceutical industry. They enhance solubility, bioavailability and stability of many drugs. Recently, several of CD derivatives have been synthetized in order to improve their physicochemical properties and inclusion capacities. Based on their pharmaceutical importance, many studies demonstrated the activity of CDs in drug complexation, however, there is limited information available about their cytotoxic effects. The aim of our study was to investigate the cytotoxic properties of various CD derivatives. We performed MTT cell viability assays on the Caco-2 human colon carcinoma cell system. In addition, we investigated cholesterol-CD complexation by an HPLC method, which determined the cholesterol content of the cholesterol-CD complex. The viability tests showed significant differences between the cytotoxicity of the CD derivatives. Cell toxicity of methylated CDs decreases DIMEB>TRIMEB>RAMEB. The anionic carboxymethylated derivative (CMBCD) and cationic quaternary amino beta-cyclodextrin (QABCD) proved to be less toxic than the methylated ones. Most of the second generation CD derivatives, which contain ionic substituents beside the methyl groups, showed less cytotoxicity than the parent compounds, only succinyl random methylated beta-CD (SU-RAMEB) and RAMEB represent the similar toxicological properties on Caco-2 cells. Harmful attributes of RAMEB, DIMEB and their cholesterol complexes were also investigated in our in vitro system. RAMEB and DIMEB cholesterol complex derivatives showed slight cytotoxic effects compared to the parent compounds. In conclusion, our studies demonstrated a significant correlation between the cytotoxic effect and the cholesterol complexation attributes of CD derivatives.     

Chemically cross-linked and grafted cyclodextrin hydrogels: From nanostructures to drug-eluting medical devices

The unique ability of cyclodextrins (CDs) to form inclusion complexes can be transmitted to polymeric networks in which CDs are chemically grafted or cross-linked. Combination of CDs and hydrogels in a single material leads to synergic properties: the hydrophilic network enhances biocompatibility and prevents dilution in the physiological medium increasing the stability of the inclusion complexes, while CDs finely tune the mechanical features and the stimuli-responsiveness and provide affinity-based regulation of drug loading and release. Therefore, CD-functionalized materials are opening new perspectives in pharmacotherapy, emerging as advanced delivery systems (DDS) for hydrophobic and hydrophilic drugs to be administered via almost any route. Medical devices (catheters, prosthesis, vascular grafts, bone implants) can also benefit from surface grafting or thermofixation of CDs. The present review focuses on the approaches tested to synthesize nano- to macro-size covalently cross-linked CD networks: i) direct cross-linking through condensation with di- or multifunctional reagents, ii) copolymerization of CD derivatives with acrylic/vinyl monomers, and iii) grafting of CDs to preformed medical devices. Examples of the advantages of having the CDs chemically bound among themselves and to substrates are provided and their applicability in therapeutics discussed.     

Cyclodextrins in transdermal and rectal delivery

Transdermal and rectal routes of drugs are very important as a useful supplement of oral routes and the direct exposing method of drugs when the systemic and local effects are required. The widespread use of parent cyclodextrins (CDs) and chemically modified CD derivatives (CD derivatives) for in-vitro and in-vivo dermal and rectal drug delivery have been evaluated. In addition, the application of hydrophilic CD derivatives to cosmetics have been progressing. In this article, the current status of parent CDs and CD derivatives in the transdermal and rectal delivery of conventional low molecular weight agents are reviewed.