Preparation of nanoparticles composed of chitosan and its derivatives as delivery systems for macromolecules

Three different kinds of nanoparticles for paracellular transport were prepared using a simple and mild ionic‐gelation method. Sodium tripolyphosphate (TPP) as crosslinking agent was added into three kinds of solutions, which were chitosan solution, physical blending solution of chitosan, and glycidyl trimethylammonium chloride (GTMAC), and O‐(2‐hydroxyl) propyl‐3‐trimethyl ammonium chitosan chloride (O‐HTCC) solution respectively. O‐HTCC was synthesized by coupling of GTMAC to chitosan whose functional groups of the NH₂ groups were protected. The nanoparticles were characterized by transmission electron microscopy, atomic force microscopy, photon correlation spectroscopy, and zeta potential measurement. The results showed that increasing TPP concentration promoted the size of chitosan nanoparticles, a decrease in the size of O‐HTCC nanoparticles incurred on the contrary. The size of O‐HTCC nanoparticles is slightly bigger than that of pure chitosan nanoparticles, and smaller than that of physical blending nanoparticles (PBN). Bovine serum albumin (BSA), as a model protein drug, was incorporated into the nanoparticles. Compared with chitosan nanoparticles and PBN, high BSA loading efficiency (87.5%) and loading capacity (99.5%) are achieved by quaternized chitosan (O‐HTCC) nanoparticles, and the release profile of BSA from nanoparticles has an obvious burst effect and a slowly continuous release phase followed. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 2007     

壳聚糖表面活性剂的制备及其表面性能

以壳聚糖为原料制备系列O-羟丙基-N-烷基化壳聚糖表面活性剂Cn-HPCS。通过IR和1HNMR对Cn-HPCS的结构进行表征;通过测定其表面张力(γ),临界胶束浓度(cmc),HLB值和泡沫性能等对其表面性能进行评价。结果表明,Cn-HPCS的cmc为0.016～0.05 mmol/L,HLB值为5.33～13.89,并具有良好的泡沫性能且乳化性能优于Tween 60。     

壳聚糖季铵盐研究进展

壳聚糖是应用广泛的天然多糖,资源丰富,壳聚糖化学改性后得到的衍生物改善了壳聚糖的功能,并保留了壳聚糖本身的可生物降解性、生物相容性等优点.其中壳聚糖的季铵盐改性明显提高了其抑菌、抗氧化等活性,并增强了壳聚糖的水溶性,近年来研究较多,介绍了壳聚糖季铵盐的化学改性及应用研究进展,这些化学改性方式均在一定程度上提高了壳聚糖的...     

Synthesis and characterization of chitosan/cloisite 30B film for controlled release of ofloxacin

In this research program, chitosan film was prepared by blending chitosan with Cloisite 30 B at different concentrations 0 wt %, 1 wt %, and 2.5 wt %. The blends were characterized by Fourier transmission infrared spectroscopy (FTIR), scanning electron microscopy (SEM), X‐ray diffraction (XRD) analysis. From the FTIR spectra the various groups present in chitosan/C 30 B blend were monitored. The homogeneity, morphology, and crystallinity of the blends were ascertained from SEM and XRD data, respectively. The most suitable form of blend was taken and used as a carrier for the controlled release of ofloxacin. The swelling studies have been carried out at different drug loading. Drug release kinetics was analyzed by plotting the cumulative release data versus time by fitting to an exponential equation which indicated the occurrence of non‐Fickian type of kinetics. The drug release was investigated at different pH medium and it was found that the drug release depends upon the pH medium as well as the nature of matrix. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012     

Synthesis and antimicrobial activity of Schiff base of chitosan and acylated chitosan

Chitosan, a biocompatible, biodegradable, nontoxic polymer, is prepared from chitin, which is the second most naturally occurring biopolymer after cellulose. Schiff base of chitosan, sorbyl chitosan, and p‐aminobenzoyl chitosan were synthesized working under high‐intensity ultrasound and their antimicrobial properties were analyzed against Escherichia coli, Staphylococcus aureus, and Aspergillus niger. The structures of the derivatives were characterized by FTIR spectroscopy and elemental analysis. The results of antimicrobial activities indicated that the antimicrobial activities of the derivatives increased with increasing the concentration. The antibacterial activity of schiff base of chitosan against E. coli was stronger, while acylated chitosan had better inhiting effect on S. aureus than others. It was also found that the antifungal activities of the derivatives were stronger than that of chitosan, and schiff base of chitosan was obviously superior to acylated chitosan. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012     

Therapeutic effect of chitosan modification on salmon-calcitonin-loaded PLGA nanoparticles

Although salmon-calcitonin (sCT) has been known as a potent drug for the treatment of osteoporosis, its oral dosage form products have not been commercially available primarily due to a poor oral bioavailability. Chitosan has been extensively examined as a potential oral absorption enhancer, whereas encapsulation with PLGA has been widely studied to address the delivery problems of typical peptide drug molecules. We investigated the mechanism and therapeutic effect of chitosan modification on the sCT-loaded PLGA nanoparticles. Chitosan was added onto these particles in two ways: by incorporation during W/O/W emulsification and by solid dipping. Particles were characterized by particle size analyzer, Zeta potential analyzer, scanning electron microscopy, and so forth. Nano-sized particles of 430–590 nm in fairly spherical shape with a narrow size distribution were produced. The PLGA encapsulation efficiency greater than 50% of added sCT was achieved regardless of chitosan modification. It turned out that sCT-loaded PLGA particles with chitosan modified during W/O/W emulsification (referred to as sCT-PLGA-CHT1) showed better therapeutic behavior in terms of sustained release effects as well as short-period hypocalcemic effects than the others. It was concluded that the beneficial effect was greatly associated with the formation of embedded structure of chitosan molecules when particles were modified with chitosan.     

Preparation and characterization of chitosan films,crosslinked with symmetric aromatic dianhydrides to achieve enhanced thermal properties

This study has developed a new generation of crosslinked chitosan‐based films using symmetric aromatic dianhydrides as crosslinking agents. The formation of the dianhydride‐crosslinked chitosan hydrogel films was confirmed using Fourier transform infrared and solid‐state ¹³C NMR spectral analyses. The films obtained from these derivatives were characterized by their thermal, swelling and hydrophilic properties. The results showed that introducing a cyclic imide moiety into the chitosan matrices played a significant role in enhancing the thermal properties of these chitosan films. It was found that even at high levels of substitution, thermal stability of the studied chitosan derivatives was improved, in spite of a reduction in crystallinity. Heterocyclic imide linkages produced networks that were insoluble in both acidic and alkaline media but allowed swelling in aqueous media. An increase in the hydrophobicity of the chitosan film surfaces was observed after introduction of the cyclic imide moiety. These engineered films produced noteworthy results concerning their thermal and swelling properties. There is a need to further investigate these films for drug delivery and biomaterials applications. © 2014 Society of Chemical Industry     

羧烷基-季铵两性壳聚糖的制备及其阻垢杀菌性能

采用氯乙酸、丙烯酸和2,3-环氧丙基三甲基氯化铵对壳聚糖（CTS）改性,制得羧甲基-季铵壳聚糖（CMQAC）和羧乙基-季铵壳聚糖（CEQAC）,并通过IR、1H NMR、XRD对产物进行了结构确证。用静态阻垢的方法对两性壳聚糖衍生物阻硫酸钙垢的性能进行了评价,结果表明两性壳聚糖用量为16 mg/L、[Ca2＋]〈2000 mg/L、[SO42-]〈4800 mg/L时,阻垢率可达到100%。用小瓶测试法测定不同季铵取代度（DS）的两性壳聚糖对异养菌的杀菌效果。研究结果表明,在用量为30 mg/L时,CMQAC季铵取代度为0.73时杀菌率为99.7%,CEQAC季铵取代度为0.50时杀菌率为99.2%,改性后壳聚糖衍生物的阻垢和杀菌性能与壳聚糖相比有了明显提高。     

转谷氨酰胺酶促壳聚糖/壳聚糖衍生物对蛋白质糖基化 作用的研究进展

转谷氨酰胺酶途径糖基化具有效率高、特异性高、安全性高等优点被广泛地应用于蛋白质改性。为了研究采用转谷氨酰胺酶途径进行蛋白质糖基化对蛋白质功能性质、结构的影响,本文对国内外该途径糖基化的研究现状进行综述。首先介绍了糖基化选用的代表性多糖——壳聚糖及其衍生物,以及转谷氨酰胺酶催化蛋白质与多糖交联的机理。然后,重点阐述了酶法糖基化对蛋白质表面疏水性、溶解性、乳化性等加工性能的影响,以及对蛋白质结构变化的影响,包括一级结构、二级结构、微结构。其次,对目前该法修饰蛋白质在可食膜、医用敷料、抑制晚期糖基化终末产物方面的应用做了简要介绍,充分显示其在各领域的应用价值。最后展望了转谷氨酰胺酶途径蛋白质糖基化的未来研究方向和亟待解决的问题。     

壳聚糖衍生物的表面活性及其药物增溶性研究进展

壳聚糖基表面活性剂具有安全无毒和可生物降解等特点,在生物医药和日用化工等行业的应用日益增多。通过双亲性改性获得具有表面活性的壳聚糖所形成的胶束,可以增加难溶药物的溶解度,延长释药时间,提高药物利用率,降低细胞毒性,在药物载体方面具有广阔的应用前景。本文综述了近年来偶联、烷基化、酰基化、羧甲化、季铵化等改性壳聚糖衍生物的表面活性研究以及对紫杉醇、喜树碱、阿霉素和甲氨基叶酸等药物的增溶应用进展。在壳聚糖的改性新方法中有两点值得注意：一是利用疏水相互作用构成自组装体;二是引入具有特殊功能的基团制备智能载药胶束。     

壳聚糖的研究进展及应用

介绍了传统法和降解法制备壳聚糖的两种方法。降解法因工艺简单、产率高、无污染等优点,目前得到广泛的应用。综述了壳聚糖在食品工业、医药卫生、农业、日化以及水处理等领域的广泛应用,分析了我国目前壳聚糖的研究现状以及壳聚糖衍生物的研发前景。作为一种资源丰富、用途广泛的天然高分子化合物,壳聚糖及其衍生物的市场前景十分可观。     

Flocculation performance of modified chitosan in an aqueous suspension

A cationic moiety, N‐(3‐chloro‐2‐hydroxypropyl)trimethyl ammonium chloride (CHPTAC), was incorporated onto chitosan in an aqueous alkaline solution. Thus, modified chitosan was prepared. A series of modified chitosans with different molecular weights and charge densities were synthesized through the alteration of the molar ratio of CHPTAC to chitosan in the reaction mixture. The synthesized modified chitosans were thereafter characterized by a variety of physicochemical characterization techniques to confirm that modification did take place. Furthermore, the feasibility of applying modified chitosans as flocculants was assessed, and they were compared with the native chitosan in model colloidal suspensions of kaolin and iron‐ore powder. The results indicated that the unmodified chitosan itself was a good flocculating agent. The flocculation performance of the chitosan could be altered by the incorporation of the CHPTAC moiety. Studies showed that not all the modified chitosans had superior flocculation performance versus the native chitosan. Among the different grades, the modified chitosan with a moderate molecular weight and a moderate charge density showed the best flocculation performance in both model suspensions. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

PEGylated chitosan derivatives: Synthesis, characterizations and pharmaceutical applications

This review sets out to describe and discuss the synthetic approaches and the fields of application of PEGylated chitosan copolymers especially for medical use. The PEGylation of chitosan and chitosan derivatives is able to add new physicochemical properties to the cationic polysaccharide polymers, thereby overcoming some limitations, especially regarding their solubility and their use in drug and gene delivery (DNA and siRNA). All methods of derivatization have been considered and described together with the different methods of characterization of the copolymers. The capacities of PEGylated chitosan to reduce chitosan toxicity, to enhance membrane permeation and to form thermosensitive hydrogels have also been discussed.     

几丁聚糖在促进药物吸收中的应用

大量的体内、体外实验表明,几丁聚糖及其衍生物具有良好的生物粘附性,能促进药物吸收,是非常有前景的药物吸收促进剂。讨论了几丁聚糖及其衍生物促进药物吸收作用的机制、影响因素,以及发展趋势。     

Novel physical hydrogels composed of opened‐ring poly(vinyl pyrrolidone) and chitosan derivatives: Preparation and characterization

A novel, physically stabilized hydrogel system composed of chitosan (Chi) or its derivatives [e.g., carboxymethyl chitosan (CMC), sodium carboxymethyl chitosan, or trimethyl carboxymethyl chitosan (TMCMC)] with poly(vinyl pyrrolidone) (PVP) or opened‐ring poly(vinyl pyrrolidone) (OR–PVP) were prepared and characterized. TMCMC was synthesized by a novel method with dimethylsulfate as the methylation agent. The synthesized materials were characterized by Fourier transform infrared spectroscopy, ¹H‐NMR, ¹³C‐NMR, and size exclusion chromatography. The mechanical properties, gel fraction, swelling behavior, and water state of the prepared hydrogels were investigated. Gelation occurred when the OR–PVP and Chi solutions were blended within a few seconds. However, the gelation of the OR–PVP and CMC solutions needed pH adjustment. No gelation occurred when the solutions of TMCMC and PVP or OR–PVP were blended. The quaternization or protonization of  NH₂ groups may have prevented the gelation of the solutions. The amino groups of Chi derivatives should have been free to take part in hydrophilic bonds between the two polymers. The physical entanglement of polymeric chains and strong hydrogen bonds between the polymers were considered as mechanisms for the formation of the physical hydrogels. The physical hydrogels showed ionic and pH‐sensitive swelling properties. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Role of the alkyl moiety and counter ions on the thermal stability of chitosan derivatives

The thermal stability of alkyl chitosan derivatives (RChi) and N,N,N‐trimethyl chitosan bearing different counter ions (TMCX) was assessed by means of TG analyses. Multistep TG curves were observed for TMCX regardless of the counter ion. They exhibited lower DTG peak temperatures (TMCCl/238.2°C, TMCBr/224.5°C, TMCI/222.6°C, and TMC‐SO₄/237.0°C) as compared to the parent chitosan (306.4°C) while, in contrast, the RChi showed higher DTG temperatures (ButChi/311.7°C, OctChi/327.8°C, and DodecChi/306.3°C). The apparent activation energy values determined by using the isoconversional method revealed that the RChi derivatives have low activation energy (OctChi/111.6 ± 5 kJ/mol), whereas quaternary salts have high activation energy (TMCI/155.5 ± 10 kJ/mol). © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

High flux and rejection with chiral chitosan composite nanofiltration membranes: Preparation and characterization

Two series of novel composite nanofiltration (NF) membranes were prepared by the overcoating of polysulfone ultrafiltration membranes with a mixture of chitosan and chitosan derivatives modified with two different chiral compounds. The two chiral compounds and their chitosan derivatives were characterized by IR spectroscopy, differential scanning calorimetry, and polarimetry. The structure of the membrane was characterized by scanning electron microscopy (SEM). The rejection and flux of the composite NF membranes were strictly related to the chiral compound grafted to chitosan and its composition in the mixture. An extremely high rejection, 98.23%, was observed with P_2–3 of the polymer (P₂) composite NF membrane, and the flux remained as high as 351 L m^?2 h^?1 at 0.4 MPa with 1000 mg/L NaCl. These results, together with SEM and IR images of the composite NF membrane, indicated that the chiral compound structure was crucial for the structure and function of the composite membrane. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013     

Preparation and characterization of a novel thermosensitive hydrogel based on chitosan and gelatin blends

In this study, a novel injectable in situ gelling thermosensitive hydrogel system based on chitosan and gelatin blends was designed and investigated. The addition of gelatin provides the correct buffering and other physicochemical conditions including control of hydrophobic interactions and hydrogen bonding, which are necessary to retain chitosan in solution at neutral pH near 4°C and furthermore to allow gel formation upon heating to body temperature. The chitosan/gelatin hydrogels were studied by FTIR, swelling, and rheological analysis. The rheological analysis evidenced the endothermic gelation of chitosan/gelatin solutions, which indicated their gelation temperatures and reflected the effect of gelatin concentration on the thermosensitive properties of gels. The morphology of this system was examined with laser scanning confocal microscopy and scanning electron microscopy. The images indicated that the gels were quite heterogeneous and porous. The investigation of these gels as vehicles for delivering bovine serum albumin as a model drug of protein showed that the system could sustain the release of the protein drug. These results show that chitosan/gelatin solutions can form gels rapidly at body temperature and have promising perspective for their use in local and sustained delivery of protein drug. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Synthesis and characterization of chitosan derivatives carrying galactose residues

A series of water‐soluble chitosan derivatives, carrying galactose residues, were synthesized by using an alternative method in which the galactose groups were introduced into amino groups of the derivatives. First, hydroxyethyl chitosan (HECS) and hydroxypropyl chitosan (HPCS) were synthesized under alkaline conditions by using chitosan and propylene or chitosan and ClCH₂CH₂OH as the starting materials, respectively. Then lactobionic acid was added into the systems so as to form galactosylated HECS (Gal‐HECS) and galactosylated HPCS (Gal‐HPCS) with substitution degrees of 53 and 47%, respectively. Lactosaminated HPCS (Lac‐HPCS) and Lactosaminated HECS (Lac‐HECS) were obtained with substitution degrees of 42 and 38%, respectively, by the reductive amination of the mixtures of lactose and HECS or lactose and HPCS with potassium borohydride present in the reaction. The chemical structures of new chitosan derivatives were characterized by FTIR, ¹H NMR, ¹³C NMR, and elemental analysis. Some physical properties were also analyzed by wide angle X‐ray diffraction (WAXD) and differential scanning calorimetry (DSC). The novel chitosan derivatives carrying galactose residues may be used as additives for hepatic targeting delivery. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 97: 2161–2167, 2005     

Preparation of macroporous chitosan patch using co-solvent as a transdermal drug-delivery system

As a simple method, bio-patches of band type have been widely used in various medical areas for more than 70 years. Despite their numerous advantages, drawbacks such as a lack of adhesive strength and low efficiency of transdermal drug delivery have limited their application. To improve the convenience of use, a 3D porous chitosan patch was prepared simply by phase separation of a solvent (acidic water)/co-solvent [dimethyl carbonate (DMC)]. As a tackifìer of low cytotoxicity, allyl 2-cyanoacrylate bio-glue was prepolymerized and coated onto the porous chitosan patch. Various properties were examined, such as mechanical strength, efficiency of drug-delivery, morphology, cytotoxicity and degradability. We ascertained that the optimal ratio of co-solvent for achieving a highly porous chitosan patch was DMC at a ratio of 5 %. The resultant drug release by the optimal highly porous chitosan patch was approximately twofold faster than that of the untreated control. The porous patch showed improved efficiency of cell adhesion after culturing in cells for 4 h. After 72 h, the cultured cells showed increased cell proliferation on the porous patches. These results strongly suggest that the chitosan-based porous patches covered with modified cyanoacrylate can be widely used as good adhesive patches in various incidents.