Preparation and characteristic of lactose‐oleoylchitosan and the application of its self‐aggregates as drug delivery system

Amphiphilic polymers lactose‐oleoylchitosan (Lac‐OCH) with different degree of substitution (DS) of lactose were prepared. The chemical structure of the new chitosan derivative was tested and verified. The rheological features including solubility and viscosity of Lac‐OCH were investigated. The introduction of hydrophilic group lactose could improve the solubility of the polymer and Lac‐OCH was soluble in acetic acid solution under pH 7.0. The viscosity of Lac‐OCH decreased a little along with the increasing of DS of lactose. Lac‐OCH with high DS, middle DS, and low DS of lactose possessed small critical aggregation concentration value, and the critical aggregation concentration value rised along with the increasing of DS of lactose. However, the affect was not obvious. In brief, the CAC values were 0.0325, 0.0340, and 0.0344 mg/mL corresponding to the samples of low DS, middle DS, and high DS. Lac‐OCH, obtained by hydrophilic modified using lactose, could also form self‐assembled nanoparticles by oil/water (O/W) emulsification method comparing with OCH. The Lac‐OCH nanoparticles showed dense, axiolitic texture, and the average diameter was approximate 200 nm. The sustained‐release characteristics of Lac‐OCH nanoparticles were studied using Doxorubicin as model drug. The results revealed the promising potential of amphiphilic Lac‐OCH as drug carrier. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Composite films of N,O‐carboxymethyl chitosan and bamboo fiber

To obtain an antibacterial chitosan derivative, composite films of N,O‐Carboxymethyl Chitosan (N,O‐CMCS) and bamboo fiber were prepared. A water‐soluble chitosan derivative‐N,O‐CMCS was synthesized from chitosan with chloroacetic acid in alkaline solution. Composite films with 1–5 wt % N,O‐CMCS content were prepared in NaOH/urea/thiourea solution. The DS of N,O‐CMCS reached 1.70 and the water solubility increased with the increasing of DS. The carboxymethyl group was introduced into chitosan, which led to the decrease of thermal stability and crystallinity. The structural characterization confirmed that N,O‐CMCS was adsorbed on the surface of bamboo fiber. The antibacterial performance of the composite films were enhanced with the increasing of N,O‐CMCS content. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 39851.     

壳聚糖醋酸溶液中聚集体形貌研究

采用稳态荧光技术和原子力显微镜研究了DD88％壳聚糖醋酸溶液中的聚集行为。30℃0．3mol／L醋酸溶液中壳聚糖的临界聚集浓度为1.5g／L。低于临界聚集浓度时,壳聚糖聚集体表现为大量高度约0．6～3．5nm、轮廓长度约120-340nm的小尺寸聚集体和少量尺寸分布不均一的高度约为8nm,轮廓长度200～400nm的大尺寸聚集体,高于临界聚集浓度时,大尺寸聚集尺寸增加,分布变宽。     

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     

Graft copolymerization of methyl acrylate onto chitosan initiated by potassium diperiodatoargentate (III)

A novel efficient redox system—potassium diperiodatoargentate [Ag(III)]‐chitosan—was employed to initiate the graft copolymerization of methyl acrylate (MA) onto chitosan in aqueous alkali solution. The effects of reaction variables such as monomer concentration, initiator concentration, reaction time, and temperature were investigated and the grafting conditions were optimized. The structures and the thermal stability of chitosan and chitosan‐g‐PMA were characterized by infrared spectroscopy (IR) and thermogravimetric analysis (TGA). The solubility of chitosan‐g‐PMA in some mixed solvent was tested. The graft copolymer was shown to be an effective compatibilizer in blends of poly(vinyl chloride) (PVC) and chitosan. Finally, a mechanism is proposed to explain the formation of radicals and the initiation. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 101: 799–804, 2006     

Measurement of critical concentration for mesophase formation of chitosan derivatives in both aqueous and organic solutions

A novel chitosan derivative, acryloyl chitosan (AcCs), and two N‐maleoyl chitosans, MaCs‐1 and MaCs‐2, with different degrees of substitution were synthesized using completely deacetylated chitosan as raw material under different reaction conditions. AcCs is an amphiphilic chitosan derivative, but MaCs‐1 and MaCs‐2 are soluble in water and organic solvents respectively. The concentrated solutions of AcCs, MaCs‐1 and MaCs‐2 all demonstrated mesophases and were investigated using polarizing optical microscopy (POM). Circular dichroism (CD) was also employed for determining the critical concentration for mesophase formation. A broad peak in the visible light region of CD spectra had its origin in the appearance of the mesophase, and arose from the selective reflection of cholesteric helix pitches. The results of CD measurements agreed with those of POM. The critical concentration values for aqueous solutions were much lower than those for organic solutions, which was explained by the strong interactions between the chitosan derivatives and water. Copyright © 2006 Society of Chemical Industry     

Antibacterial effects of chitosan and its water‐soluble derivatives on E. coli,plasmids DNA,and mRNA

The antibacterial activities of chitosan and its water‐soluble derivatives on E. coli were studied according to four influencing factors in vitro. The antibacterial study showed that chitosan, O‐hydroxyethyl chitosan (O‐HECS), and O‐carboxymethyl chitosan (O‐CMCS) could inhibit the growth of the microbial. To study the antibacterial mechanism, plasmid DNA pBR322 and pUC18 were selected to be the probes to find out the binding abilities of chitosans. Results showed that raw chitosan had a high binding ability with the plasmids and the influencing degrees were stable. The effects of chitosan derivatives on plasmids might be affected by space effect and static effect. With appropriate concentrations and molecular weights, the derivatives might have strong abilities to combine with DNA. The degree of influence of chitosan and its derivatives on plasmids had nothing to do with time. The experiment focusing on the relationship between chitosans and mRNA showed that O‐CMCS would hinder the synthesis of mRNA, and this may give some proof to its antibacterial mechanism. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103: 3521–3528, 2007     

Preparation and antimicrobial activity of sulfopropyl chitosan in an ionic liquid aqueous solution

To improve the solubility and antibacterial activity of chitosan and expand its applications, we synthesized sulfopropyl chitosan (SP‐CS) with various degrees of substitution (DSs) under mild and green reaction conditions in the aqueous solution of an ionic liquid by a green process. The chemical structures of the polymers were verified by Fourier transform infrared spectroscopy and ¹H‐NMR, and the thermal stability was studied by thermogravimetric analysis. After modification, the water solubility of chitosan was improved significantly, and SP‐CS showed excellent solubility in water at neutral pH. The antibacterial activities of the SP‐CSs with various DSs were systematically studied for the first time by the Oxford cup method and optical density method. The results suggest that the antimicrobial properties of SP‐CS were enhanced by the introduction of sulfopropyl and increased with increasing DS. The application of chitosan could be expanded, and SP‐CS has the potential to be used as a water‐soluble antimicrobial. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134, 44989.     

Synthesis and property studies of N‐carboxymethyl chitosan

N‐carboxymethyl chitosans (N‐CMC) were synthesized from chitosan in water with chloroacetic acid instead of comparatively expensive glyoxylic acid. The optimal reaction conditions were 90°C and 4 h with a ratio of chloroacetic acid to chitosan 5 : 1(w/w). The degree of substitution of product exceeded 1.32. The N‐carboxymethyl chitosans were characterized by XRD, FTIR, ¹H‐NMR, and the water solubility and isoelectric point of N‐CMC with different degrees of substitution were determined. FTIR and ¹H‐NMR data has confirmed that the substitution reaction occurred on the amino groups. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Blend films of O‐carboxymethyl chitosan and cellulose in N‐methylmorpholine‐N‐oxide monohydrate

To introduce N‐methylmorpholine‐N‐oxide (NMMO) process to prepare antibacterial lyocell fiber, the blend films of O‐carboxymethyl chitosan (O‐CMCS) and cellulose were prepared. O‐CMCS in aqueous suspension with particles having a surface mean diameter of 2.24 μm was blended with cellulose in NMMO hydrate. The blend films with different O‐CMCS content were prepared with the blend solutions. SEM confirmed that O‐CMCS remained within the cellulose film in the particle. The mechanical properties of the blend films show little increased value when O‐CMCS was less 5%; however, it decreased sharply when O‐CMCS was over 8%. Thus, the optimum O‐CMCS content may give a good combination of antibacterial action and mechanical properties. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 102: 4601–4605, 2006     

Synthesis,Characterization, and Performance of a Novel Polymeric Cationic Surfactant Based on Low Molecular Weight Chitosan and 3‐Chloro‐2‐Hydroxypropyl Dimethyl Dehydroabietyl Ammonium Chloride (CHPDMDHA)

A series of novel polymeric cationic surfactants based on low molecular weight chitosan (LWCS) and 3‐chloro‐2‐hydroxypropyl dimethyl dehydroabietyl ammonium chloride (CHPDMDHA), LWCS‐g‐CHPDMDHA, were obtained by the grafting modification of LWCS with CHPDMDHA as grafting agent. The structure of LWCS‐g‐CHPDMDHA was confirmed by FT‐IR and ¹H NMR, and the degree of quaternizing substitution (DS) of LWCS‐g‐CHPDMDHA was determined according to the results of elemental analysis. The aggregation behavior and surface activities of LWCS‐g‐CHPDMDHA in aqueous solution were investigated by transmission electron microscopy (TEM) and determination of surface tension, respectively. The experimental results showed that the DS and molecular weight (M_w) of LWCS have significant influence on the critical micelle concentrations (CMC) and the surface tensions at the CMC (γ_cmc). The shape of aggregates changed with the variation of concentration of LWCS‐g‐CHPDMDHA in aqueous solution. When the LWCS‐g‐CHPDMDHA was utilized as an emulsifier, the increase of DS of LWCS‐g‐CHPDMDHA and M_w of LWCS were favorable for improving the stability of emulsions composed of water and benzene.     

Low molecular weight water‐soluble chitosans: Preparation with the aid of cellulase,characterization, and solubility

Preparation of water‐soluble chitosan (WSC) was made by treating partially N‐deacetylated chitosan with acetic anhydride in aqueous acetic acid. The optimal conditions of preparing WSC were determined on the basis of orthogonal tests. Low molecular weight WSC with broad molecular weight (600–1.5 kDa) were obtained by the depolymerization of WSC using cellulase at optimum condition of pH 4.5 and 60°C. The solubility of WSC in water and aqueous organic solvents was investigated in detail. Weight–average molecular weight (M_w) and molecular weight distribution (M_w/M_n) of samples were measured by gel permeation chromatography. The structure of WSC and its degraded products were characterized by XRD, FTIR, and MALDI‐TOF MS. The decrease of molecular weight led to transformation of crystal structure and the increase of solubility, but the chemical structures of residues were not modified compared to WSC, which was not hydrolyzed. The solubility of the WSC in water and aqueous organic solvents increased with the decrease of molecular weight. The solubility of the WSC with low molecular weight was rather high even in aqueous dimethylacetamide and dimethylsulfoxide. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 102: 1098–1105, 2006     

Synthesis and rheological behavior of a novel N‐sulfonate ampholyte chitosan

Modified chitosan derivatives with different degrees of substitution varying from 0.17 to 0.96 were synthesized by the heterogeneous reaction of chitosan with 3‐chloro‐2‐hydroxy propanesulfate in a neutral aqueous solution. The modified chitosans with a degree of substitution higher than 0.36 were soluble in water, whatsoever the pH. The structures of the polymers were characterized by Fourier transform infrared and ¹H‐nuclear magnetic resonance spectroscopies. The potentiometric titration revealed that the modified chitosan had an isoelectric point at around pH = 5.7, and its rheological behaviors in aqueous solution were studied under different conditions. The results showed that the modified chitosan had typical polyampholyte characteristics, which exhibited polyelectrolyte effect at pH = 1.7 or 13 and antipolyelectrolyte effect at pH = 8. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Chitosan/OA nanoparticle as delivery system for celecoxib: Parameters affecting the particle size,encapsulation, and release

Self‐assembled nanoparticles prepared from amphiphilic chitosan/oleic acid (Ch/OA) have shown antibacterial activity and potential application as a carrier for hydrophobic anticancer drugs. In this study, a low molecular weight chitosan was modified with oleic acid obtaining a degree of substitution (DS) of 12%. The critical aggregation concentration (CAC) of the Ch/OA polymer obtained (0.025 mg mL^?1) is lower in comparison with some systems of chitosan‐fatty acids. The self‐assembled Ch/OA nanoparticle size was optimized by changing polymer concentration, solvent, method, and time of homogenization to obtain particles with sizes around 300 nm and positive zeta potential. The drug loading about 7 μg mL^?1 and encapsulation efficiency of 75.8 ± 3.6% for Celecoxib was affected by the drug concentration. In vitro release behavior performed in (PBS, pH 7.4) and MES buffer (pH 6) indicated a pH‐dependent drug release behavior. The self‐assembled systems show stability during 4 weeks after the encapsulation of the hydrophobic drug. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134 , 44472.     

Optimizing preparation of NaCS–chitosan complex to form a potential material for the colon‐specific drug delivery system

A novel polyelectrolyte complex (PEC) formed by sodium cellulose sulfate (NaCS) and chitosan was prepared as a candidate material for colon‐specific drug delivery system. It was found in experiments that the properties of two raw materials and the process parameters, such as the degree of substitution (DS) and concentration of NaCS, the viscosity and concentration of chitosan, were very important factors on the properties of the final product—NaCS–chitosan‐PEC. The preparation of NaCS–chitosan complex was optimized by using response surface methodology to evaluate the effects of these parameters on the degradation properties of NaCS–chitosan in the simulated colonic fluid (SCF). The DS of NaCS was in the range from 0.2 to 0.6, the concentration of NaCS from 2 to 4% (w/v), the viscosity of chitosan from 50 to 550 mPa s, and the concentration of chitosan from 0.5 to 1.5% (w/v). A mathematical model was developed to describe the effect of these parameters and their interactions on the degradation of NaCS–chitosan complex. The optimum operation conditions for preparing NaCS–chitosan complex were determined to DS of NaCS of 0.2, the concentration of NaCS of 4.0% (w/v), chitosan viscosity of 327 mPa s, and the concentration of chitosan 0.5% (w/v), respectively. Validation of experiments with 5 confirmatory runs indicated the high degree of prognostic ability of response surface methodology. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Chitosan as an ocular drug delivery vehicle for vancomycin

The main objective of this research has been to study the efficiency of chitosan as an ocular drug delivery vehicle for topically applied vancomycin in rabbit eyes. Vancomycin 50 mg/mL was reconstituted in four preparations, namely: in Tears Naturale II?, in 0.9% w/v aqueous sodium chloride, and in 0.1% and 0.3% w/v chitosan solutions in 1% aqueous L (+)‐lactic acid. Twenty‐five microliters of vancomycin (50 mg/mL) were applied into the lower conjunctival eye sac in rabbit eyes. Tear samples were then collected after 0, 30, 60, 90, and 120 min to evaluate the pharmacokinetics of the topically applied vancomycin. Comparison of the results obtained showed that vancomycin 50 mg/mL eye drops in the 0.3% chitosan solution were similar to Tears Naturale II? in terms of bioavailability. The main conclusion to be drawn from this study is that the 0.3% w/v chitosan solution appears to be a highly promising, cost effective candidate for biomedical use as a vehicle for vancomycin ocular drug delivery. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

N-PEG’ylation of chitosan via “click chemistry” reactions

N-azidated chitosan was prepared by four different methods: using azidated epichlorohydrin, sodium azide plius sodium nitrite, trifluoromethane sulfonyl azide or imidazole-1-sulfonyl azide hydrochloride. Using the two last reagents, the degree of azidation (DA) of chitosan was up to 40% and 65%, respectively. N-azidated chitosans with DA at about 60% were insoluble in aqueous and common organic solvents but dissolved in 5% LiCl solution in N-methyl-2-pyrrolidone, one of the very few solvents for chitin. Chitosan–methoxy poly(ethylene glycol) derivatives containing triazolyl moiety (chitosan-N-TMPEG comb copolymers) were prepared for the first time by coupling via 1,3-dipolar cycloaddition between pendant azide and end alkyne groups of chitosan and MPEG, respectively. Comb copolymers chitosan-N-TMPEG with degree of substitution (DS) of chitosan equal to DA of chitosan were synthesized at a certain excess of MPEG alkyne reaching DS up to 40%. “Clicking” of MPEG alkyne onto azidated chitosan was successful in binary mixture of water and methylene chloride but failed in 5% LiCl solution in N-methyl-2-pyrrolidone. Significant breakdown of chitosan backbone took place under “clicking” of MPEG in the presence of Cu(II)/ascorbate catalyst resulting in graft copolymers with bimodal MWD. Chitosan-N-TMPEG copolymers contained a certain residual amount of Cu and were soluble in acetate buffer (pH 3.7). Novel comb copolymers were characterized by FT-IR and ¹H NMR spectroscopy, SEC with triple detection, intrinsic viscosity, elemental and functional group analysis.     

Effect of recovery methods and conditions on the yield,solubility, molecular weight,and creep compliance of regenerated chitosan

The objective of this study is to explore the effect of using different recovery methods and conditions on the yield, solubility, molecular weight, and creep compliance of the regenerated chitosan. The results show that yields obtained by dialysis were higher than those using recovery medium of alkali solutions, organic solvents, or alkali–alcohol–water mixtures. For those chitosans employing alkali solutions as the recovery medium, the higher the alkali concentration used, the higher the yields obtained, although the total quantity of alkali in the solution were the same. Solubilities of regenerated chitosans were similar and independent at the methods of using alkali solution, organic solvent or alkali–alcohol–water mixture or at different concentrations of alkali solution. The molecular weight of regenerated chitosan decreased from 2.37 × 10⁷ to 1.68 × 10⁷ Da proportionally with the concentration of the alkali solution of the recovery medium from 1N to 8N. Creep compliance of regenerated chitosan gel obtained from 65% degree of deacetylation (DD) chitosan was lower than that of either 72 or 89% DD chitosan gel. Of the same DD chitosan, compliance of regenerated chitosan gels obtained by using a higher concentration of alkali solution was lower than that of a lower concentration ones. Hydrogels regenerated from different DD chitosans and/or different recovery mediums have different structure and tactile properties. Therefore, they can be used as wound dressings suited to different applications. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 84: 193–202, 2002; DOI 10.1002/app.10296     

Synthesis and self-assembly of biomimetic phosphorylcholine-bound chitosan derivatives

Biomimetic N-phosphorylcholine (PC)-chitosan derivatives (PCCs) with a phosphoramide linkage between glucosamine and PC in various degree of substitution (DS) were synthesized through Atherton–Todd reaction and subsequently hydrolysis under the mild conditions, and structurally characterized by ¹H NMR, ³¹P NMR, FT-IR and GPC. The incorporation of zwitterionic PC groups modified the hydrophilic/hydrophobic balance of chitosan derivatives to induce the formation of nanosized micelles by self-assembly in neutral aqueous solution. Fluorescence measurements revealed that the critical aggregation concentration (CAC) of PCCs solutions increased with increasing the DS of PC. The physicochemical properties of PCCs aggregates in neutral aqueous solutions were investigated by AFM and dynamic light scattering (DLS). The results confirmed that the amphiphilic PCCs copolymers can self-assemble to form nanosized spherical micelles with zeta potential between 0 and 4 mV, suggesting that the PCCs nano-aggregates were mostly covered with electrically neutral zwitterionic PC groups. Furthermore, all the PCCs samples showed low toxicity against NIH/3T3 cells after incubated for 4 h or 24 h, indicating their safety for biomedical application.     

Effect of degree of substitution and molecular weight of carboxymethyl chitosan nanoparticles on doxorubicin delivery

The aim of this study was to evaluate the potential of carboxymethyl chitosan (CM‐chitosan) nanoparticles as carriers for the anticancer drug, doxorubicin (DOX). Different kinds of CM‐chitosan with various molecular weight (MW) and degree of substitution (DS) were employed to prepare nanoparticles through ionical gelification with calcium ions. Factors affecting nanoparticles formation in relation to MW and DS of CM‐chitosan were discussed. By the way of dynamic light scattering (DLS), TEM, and atomic force microscopy (AFM), nanoparticles were shown to be around 200–300 nm and in a narrow distribution. FTIR revealed strong electrostatic interactions between carboxyl groups of CM‐chitosan and calcium ions. DOX delivery was affected by the molecular structure of CM‐chitosan. Increasing MWs of CM‐chitosan from 4.50 to 38.9 kDa, DOX entrapment efficiency was enhanced from 10 to 40% and higher DS slightly improved the load of DOX. In vitro release studies showed an initial burst followed by an extended slow release. The DOX release rate was hindered by CM‐chitosan with high MW and DS. These preliminary studies showed the feasibility of CM‐chitosan nanoparticles to entrap DOX and the potential to deliver it as controlled release nanoparticles. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 100: 4689–4696, 2006