Encapsulation of salicylic acid in acylated low molecular weight chitosan for sustained release topical application

Acylated low molecular weight chitosan was used to encapsulate salicylic acid (SA) for sustained release in topical delivery. Chitosan nanoparticles were prepared from the depolymerization of commercial chitosan and further acylated with short alkyl chains. The successful acylation of butyryl chitosan [low molecular weight chitosan (LMWC)‐B] were proved by Fourier transform infrared (FTIR) and ¹H‐NMR. Successful encapsulation of SA was observed by the shift of amide I band from 1648 cm^?1 in LMWC‐B to 1641–1633 cm^?1 in SA‐loaded LMWC‐B in FTIR analysis, which further confirmed with the size increment from dynamic light scattering and transmission electron microscopy analyses by comparing its unencapsulated LMWC‐B. SA release from LMWC‐B studied by Franz diffusion experiment followed Korsmeyer–Peppas model where the release component n value (0.502) indicated diffusion and polymer swelling were involved in release mechanism. The slow release study of SA showed the acylated chitosan exhibited sustained release property toward SA. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134 , 45273.     

Folic acid‐conjugated depolymerized quaternized chitosan as potential targeted gene delivery vector

Ligand‐conjugated delivery vectors that target over‐expressed cell surface receptors have a potential impact on gene therapy. In the study reported, high‐molecular‐weight chitosan was depolymerized to medium and low molecular weight and trimethylated to render the polymer soluble over a wider pH range. Folate conjugation was introduced to the quarternized derivative to improve gene transfection efficiency. Complexes of the folic acid‐conjugated trimethylated depolymerized chitosan (FTMC) with plasmid DNA (pDNA) formed core–shell nanostructured particles. Gel electrophoretic band retardation showed efficient condensation of DNA. These derivatives and their complexes with pDNA were tested for toxicity and haemocompatibility and were found to be significantly less toxic and haemocompatible than polyethyleneimine. Transfection efficiency and nuclear uptake properties were tested in the human KB oral epidermoid cell line, which over‐expresses the folate receptor in the presence of 10% serum. Among the four FTMC derivatives investigated, folic acid‐conjugated chitosan having low molecular weight and medium folate conjugation was found to be a potential vector for gene delivery applications with good transfection and nuclear uptake properties, as proved by YOYO labelling of pDNA. Copyright © 2011 Society of Chemical Industry     

Preparation and release behavior of temperature‐ and pH‐responsive chitosan material

BACKGROUND: Chitosan is a polymer with good biocompatibility which makes it promising for potential applications in the field of drug delivery. A novel kind of copolymer, P(CS‐Ma‐graft‐NIPAm), was synthesized with chitosan (CS), maleic anhydride (Ma) and N‐isopropylacrylamide (NIPAm) by grafting and copolymerization. RESULTS: The copolymers were characterized using Fourier transform infrared, ¹H NMR and ultraviolet spectroscopies, and the molecular weight and polydispersity were determined using gel permeation chromatography. The aqueous solution properties of the copolymer and the controlled delivery of coenzyme A from it were also studied. The results showed that the copolymer had temperature and pH sensitivities, and that the release of coenzyme A from the copolymer was dependent on the release medium, namely the concentration of the copolymer, pH and temperature. Higher concentrations of the copolymer absorbed more coenzyme A than lower ones. Increasing temperature accelerated coenzyme A release from the copolymer. Also, the pH of the solution had a significant impact on the release of coenzyme A. CONCLUSION: These results suggest that the novel copolymer could be used in drug delivery systems. Copyright © 2007 Society of Chemical Industry     

HEMA‐grafted chitosan for dialysis membrane applications

Chitosan was graft copolymerized with HEMA (2‐Hydroxyethylmethacrylate) for the development of blood‐compatible dialysis membranes. The permeation characteristics of HEMA‐grafted chitosan films for four different solutes creatinine, urea, glucose, and albumin was studied in vitro at 37°C for assessment of the suitability as dialysis membranes. The grafted film CH‐12.5 composition (425% grafting) showed very high permeation to creatinine by reaching the equilibrium within 45 min. The compositions CH‐7.5 and CH‐12.5 showed excellent permeation to glucose when compared to virgin chitosan films. In the case of urea permeation, all the grafted compositions exhibited higher percent permeation than the virgin chitosan films. The copolymer films CH‐7.5 and CH‐12.5 showed enhanced permeability for the high molecular weight solute, albumin. The other grafted copolymer compositions followed almost the same trend as that of chitosan for the low molecular weight solutes as well as the high molecular weight solute. The copolymer films were also found to be highly blood compatible, noncytotoxic, and biodegradable. Hence, the need for developing blood‐compatible chitosan membranes with desirable permeability properties is achieved by the graft copolymerization of HEMA onto chitosan. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 101: 2960–2966, 2006     

Effect of time/temperature treatment parameters on depolymerization of chitosan

Depolymerization of the biopolymer chitosan by an autoclaving process at 121°C and 15 psi was investigated using various treatments. Acetic acid was found to be the most effective solvent in decreasing chitosan viscosity among the six organic acids tested. The rate of viscosity decrease increased with increasing chitosan concentration. The viscosity of 1% chitosan in 1% acetic acid decreased rapidly to 91% of the initial viscosity following the initial 15 min of autoclaving. This decreased gradually to 93% and 94% in 30 and 60 min, respectively, without being adversely affected by the chitosan solution volume. The degree of deacetylation was comparable before and after autoclaving for 60 min. Chitosan at three molecular weights (M_r = 1597, 1110, and 789 kDa) decreased in molecular weight by 46%–51% in the 15‐min treatment, 55%–60% in the 30‐min treatment, and 60%–62% in the 60‐min treatment. The addition of 0.1%–1.0% (v/v) concentrations of hydrogen peroxide to the chitosan solution autoclaved for 15 min decreased viscosity by 94%–98% and molecular weight by 69%–83%. This process is a simple, timesaving, homogeneous depolymerization procedure, and it is possible to prepare partially hydrolyzed chitosan with specified molecular weights by regulating the time of treatment. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 87: 1890–1894, 2003     

Effect of immobilized neutral protease on the preparation and physicochemical properties of low molecular weight chitosan and chito‐oligomers

Neutral protease was immobilized on glutaraldehyde‐pretreated N‐succinyl chitosan hydrogel beads and the biocatalyst obtained was used for the preparation of low molecular weight chitosan and chito‐oligomers with molecular weight of 1.9–23.5 kDa from commercial chitosan. Factors affecting the chitinolytic hydrolysis were described. The degradation was monitored by gel permeation chromatography. The structure of degraded chitosan was characterized by Fourier transform infrared, X‐ray diffraction and liquid chromatography‐mass spectrometry. Immobilized neutral protease showed optimal depolymerization at pH 5.7 and 50°C. The degree of deacetylation of the hydrolysates did not change compared to that of the initial chitosan. The decrease of molecular weight led to transformation of crystal structure but the chemical structures of residues were not modified. The degree of polymerization of chito‐oligomers was mainly from 3 to 8. The method allows cyclic procedures of immobilized enzyme and N‐succinyl chitosan support utilization, and is suitable for a large‐scale production of the low molecular weight chitosan and chito‐oligomers free of protein admixtures. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 102:4185–4193, 2006     

Preparation of O‐carboxymethyl‐N‐trimethyl chitosan chloride and flocculation of the wastewater in sugar refinery

A novel water soluble amphiphilic O‐ carboxymethyl‐N‐trimethyl Chitosan chloride (CMTMC) was synthesized. The structure of this material was characterized by Fourier transform infrared (FTIR) spectroscopy, ¹³C nuclear magnetic resonance (¹³C‐NMR) spectroscopy and X‐ray diffraction (XRD) techniques. The results showed that CMTMC had been successfully prepared. To determine the flocculation performance of the synthesized amphiphilic polymer, a comparison was made among Chitosan (CS), N‐trimethyl chitosan chloride (TMC), O‐carboxymethyl chitosan (CMC), and CMTMC on the turbidity and COD removal efficiency of 1% (v/v) wastewater in sugar refinery suspensions at pH 5.0, 7.0 and 9.0 at a dosage range of 0–8 mg/L. The results showed that the water soluble amphiphilic polymer CMTMC, which contains longer polymer anion and polymer cation, had the best performance not only in turbidity removal but also in COD removal on sugar refinery wastewater. The using of CMTMC as a flocculant to treat wastewater in sugar refinery was actually more effective than CS, CMC, and TMC. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Use of chitosan to improve dyeability of DP-finished cotton (II)

Chitosan was used to improve the dyeability of DP-finished cotton. Cotton fabric was treated with a mixture of chitosan, 4,5-dihydroxy-1,3-dimethyl-2-imidazolidinone (DHDMI), and catalyst in a one-step process. To investigate the effect of molecular weight of chitosan on the dyeability of treated fabrics, six chitosan samples of different molecular weights were prepared by depolymerization with sodium nitrite; 185,300, 73,200, 59,000, 21,000, 14,000, and 3,800, respectively. Chitosan improves dye uptake of direct and acid dyes considerably, and the dye uptake increases with the increase of the molecular weight of chitosan. Reactive dye uptake increases slightly in alkaline condition as the molecular weight of chitosan decreases. Higher dye uptake is obtained in acidic condition than in alkaline condition. Chitosan treatment has no discernable effect on the colorfastness to washing, but decreases the colorfastness to wet crocking by about half a point. And chitosan affects other properties of treated fabric; lower wrinkle recovery, stiffer handle, and higher breaking strength as the molecular weight of chitosan increases. © 1998 John Wiley & Sons, Inc. J Appl Polym Sci 67:1515–1521, 1998     

Grafting of poly(3‐hydroxyalkanoate) and linoleic acid onto chitosan

Poly(3‐hydroxy octanoate) (PHO), poly(3‐hydroxy butyrate‐co‐3‐hydroxyvalerate) (PHBV), and linoleic acid were grafted onto chitosan via condensation reactions between carboxylic acids and amine groups. Unreacted PHAs and linoleic acid were eliminated via chloroform extraction and for elimination of unreacted chitosan were used 2 wt % of HOAc solution. The pure chitosan graft copolymers were isolated and then characterized by FTIR, ¹³C‐NMR (in solid state), DSC, and TGA. Microbial polyester percentage grafted onto chitosan backbone was varying from 7 to 52 wt % as a function of molecular weight of PHAs, namely as a function of steric effect. Solubility tests were also performed. Graft copolymers were soluble, partially soluble or insoluble in 2 wt % of HOAc depending on the amount of free primary amine groups on chitosan backbone or degree of grafting percent. Thermal analysis of PHO‐g‐Chitosan graft copolymers indicated that the plastizer effect of PHO by means that they showed melting transitions T_ms at 80, 100, and 113°C or a broad T_ms between 60.5–124.5°C and 75–125°C while pure chitosan showed a sharp T_m at 123°C. In comparison of the solubility and thermal properties of graft copolymers, linoleic acid derivatives of chitosan were used. Thus, the grafting of poly(3‐hydroxyalkanoate) and linoleic acid onto chitosan decrease the thermal stability of chitosan backbone. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103:81–89, 2007     

UV‐cured natural polymer‐based membrane for biosensor application

Chitosan, a natural product, is inherently biodegradable, biocompatible, and nontoxic. These properties make chitosan ideal for inclusion in matrices designed for use in enzyme immobilization for clinical analysis. This study demonstrates the feasibility of using chitosan in electrochemical biosensor fabrication. The enzyme sulfite oxidase (SOX) was covalently immobilized onto the matrix of chitosan–poly(hydroxyethyl methacrylate) (chitosan–pHEMA), a natural/synthetic polymer hybrid obtainable via UV curing. p‐Benzoquinone, which served as an electron transfer mediator, was coupled onto the polymer network for activation of the chitosan–pHEMA copolymer, after completion of the photo‐induced polymerization reaction. The biological activity of the immobilized SOX and the electroactivity of the coupled p‐benzoquinone were investigated. © 2000 John Wiley & Sons, Inc. J Appl Polym Sci 79: 466–472, 2001     

Chitosan and N‐carboxymethylchitosan: I. The role of N‐carboxymethylation of chitosan in the thermal stability and dynamic mechanical properties of its films

Chitosan (degree of deacetylation of 90.2%) and N‐carboxymethylchitosan (N‐CMCh) (degree of substitution of 18.5%) were analyzed using thermogravimetric analysis in order to determine their thermal stability. Also, their films were evaluated using scanning electron microscopy (SEM) and mechanical and dynamic mechanical analysis (DMA). Both polymers showed a thermal degradation peak at T_m ～ 250 °C, with T_onset and weight loss of 175 °C and 62% and 190 °C and 35% for chitosan and N‐CMCh, respectively. N‐CMCh showed a second thermal degradation peak at T_m = 600 °C, with an additional weight loss of 25%. Kinetic thermal analysis showed a slower process of degradation at 100 °C for N‐CMCh compared with chitosan, and an activation energy 13 times higher for the former, confirming the higher stability of N‐CMCh. Analysis of chitosan and N‐CMCh films showed that the latter support a high tension, with lower elasticity, and, as revealed by DMA, N‐CMCh has a more compact film structure, with a crossing arrangement of N‐CMCh fibers, as compared with the chitosan films which were determined from SEM analysis to have fibers in one direction only. Copyright © 2006 Society of Chemical Industry     

A new approach for the preparation of chitosan from γ‐irradiation of prawn shell: effects of radiation on the characteristics of chitosan

Chitosan is a biodegradable polymer composed of randomly distributed β‐(1,4)‐linked D ‐glucosamine (deacetylated unit) and N‐acetyl‐D ‐glucosamine (acetylated unit). It is produced commercially by deacetylation of chitin, which is the structural element in the exoskeleton of crustaceans (such as crabs and shrimps) and the cell walls of fungi. In the work reported, we developed a facile technique for the preparation of chitosan by irradiating prawn shell at various intensities from 2 to 50 kGy. It was observed that γ‐irradiation of prawn shell increased the degree of deacetylation (DD) of chitin at a relatively low alkali concentration during the deacetylation process. Among the various irradiation doses applied to prawn shell, a dose of 50 kGy and 4 h heating in 50% NaOH solution yielded 84.56% DD while the chitosan obtained from non‐irradiated prawn shell with the same reaction conditions had only 74.70% DD. In order to evaluate the effect of γ‐irradiation on the various physicochemical, thermomechanical and morphological properties, the chitosan samples were again irradiated (2–100 kGy) with γ‐radiation. Molecular weight, DD, thermal properties with differential scanning calorimetry and thermogravimetric analysis, particle morphology by scanning electron microscopy, water binding capacity (WBC), fat binding capacity (FBC) and antimicrobial activity were determined and the effects of various γ‐radiation doses were assessed. The DD, WBC, FBC and antimicrobial activity of the chitosan were found to improve on irradiation. It was obvious that irradiation caused a decrease of molecular weight from 187 128 to 64 972 g mol^?1 after applying a radiation dose of 100 kGy which occurred due to the chain scission of chitosan molecules at glycosidic linkages. The decrease of molecular weight increased the water solubility of the chitosan, the extent of which was explored for biomedical applications. Copyright © 2012 Society of Chemical Industry     

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     

Depolymerized chitosan nanoparticles for protein delivery: Preparation and characterization

In this article we describe our preliminary work involving the use of depolymerized, low molecular weight chitosan nanoparticles as carriers for proteins and peptides. We hypothesized that the molecular weight of chitosan could favorably modulate the particle and protein release characteristics for the delivery of certain bioactive macromolecules. Our primary objectives were to develop nanoparticle formulations that were stable and reproducible across a range of chitosan molecular weights and then characterize the physicochemical and in vitro release properties as functions of the polymer size. Using depolymerized fragments generated by NaNO₂ degradation of different chitosan salts, we prepared nanoparticle formulations based on ionotropic gelation with sodium tripolyphosphate (TPP). Regardless of the formulation, the nanoparticle size decreased with decreasing molecular weight and the ζ‐potential values remained unchanged. Similar comparisons were made with the encapsulation of insulin and tetanus toxoid as model proteins. The results indicated that the quantity of TPP in a given formulation has a greater effect on the protein encapsulation than the chitosan molecular weight. In fast release environments (i.e., buffered media), there was no significant molecular weight effect that could be discerned. These data lead to the conclusion that, under these experimental conditions, the chitosan molecular weight has a measurable effect on the particle properties, although this effect is modest relative to other formulation parameters (e.g., TPP content, type of protein loaded). Because these subtle differences could have dramatic effects physiologically, work is currently underway to elucidate the possible applications of depolymerized chitosans for peptide delivery in vivo. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 12: 2769–2776, 2003     

Plasma depolymerization of chitosan in the presence of hydrogen peroxide

The depolymerization of chitosan by plasma in the presence of hydrogen peroxide (H(2)O(2)) was investigated. The efficiency of the depolymerization was demonstrated by means of determination of viscosity-average molecular weight and gel permeation chromatography (GPC). The structure of the depolymerized chitosan was characterized by Fourier-transform infrared spectra (FT-IR), ultraviolet spectra (UV) and X-ray diffraction (XRD). The results showed that chitosan can be effectively degradated by plasma in the presence of H(2)O(2). The chemical structure of the depolymerized chitosan was not obviously modified. The combined plasma/H(2)O(2) method is significantly efficient for scale-up manufacturing of low molecular weight chitosan.     

Bone cell attachment and growth on well‐characterized chitosan films

Chitosan has been widely researched for bone tissue and implant applications. While initial results are promising, there are inconsistent reports regarding the biological responses. This may be due to inadequate evaluation of chitosan material properties. This study evaluated normal human osteoblast precursor cell attachment and proliferation on a series of well‐characterized chitosan films. The chitosan films exhibited a range of properties: 76–96% degree of de‐acetylation (DDA), 2400–8200 kDa viscosity‐average molecular weight, 62–90° contact angle, 0.24–2.46% residual ash, 5.3–287 µg cm^?2 residual protein and 23–40% crystallinity. There was no trend or correlation between DDA, crystallinity, contact angle, molecular weight, residual ash or protein content and the attachment or growth of bone cells on chitosan films. All films supported higher levels of bone cell proliferation than tissue culture plastic, which supports the general hypothesis that chitosans are osteocompatible. The 78 and 92% DDA chitosan films supported the most cell proliferation, approximately 16 times that of tissue culture plastic controls, but no chitosan physiochemical property correlated with the increased cell growth. The lack of correlation is hindered since more than one physiochemical property changed for each chitosan material. Data do indicate that there may be much variability in chitosan materials, and this variability may make understanding and comparing biological performance of chitosan materials difficult. These results highlight the need for systematic characterizations of chitosan materials for predictable biomedical applications. Copyright © 2006 Society of Chemical Industry     

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.     

Cellulose–chitosan interpenetrating polymer network for electro‐active paper actuator

In this article, the cellulose‐chitosan interpenetrating polymer network (IPN) films were prepared and fabricated as the electro‐active paper actuator. The characteristics of the cellulose–chitosan IPN films were examined by SEM, FT‐IR, XRD, DSC, and tensile test. The performance of the IPNs based actuator was evaluated in terms of bending displacement with respect to the actuation frequency, voltages, humidity levels, chitosan content, and time variation. It was observed that with chitosan content increasing in the IPNs, the crystallinity decreased and the network became denser, which caused the Young's modulus to increase. Chitosan content in IPNs also significantly affected the bending performance. The optimum IPN weight ratio of cellulose and chitosan was 60 : 40. The maximum bending displacement of 7.2 mm was found at 80% relative humidity level. In terms of durability, the bending lifetime at 70% humidity level was about 10 h with 17% performance degradation. More issues on the actuator performance and durability are addressed. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Study of the synthesis of chitosan derivatives containing benzo‐21‐crown‐7 and their adsorption properties for metal ions

Three new chitosan crown ethers, N‐Schiff base‐type chitosan crown ethers (I, III), and N‐secondary amino type chitosan crown ether (II) were prepared. N‐Schiff base‐type chitosan crown ethers (I, III) were synthesized by the reaction of 4′‐formylbenzo‐21‐crown‐7 with chitosan or crosslinked chitosan. N‐Secondary amino type chitosan‐crown ether (II) was prepared through the reaction of N‐Schiff base type chitosan crown ether (I) with sodium brohydride. Their structures were characterized by elemental analysis, infrared spectra analysis, X‐ray diffraction analysis, and solid‐state ¹³C NMR analysis. In the infrared spectra, characteristic peaks of C?N stretch vibration appeared at 1636 cm^?1 for I and 1652 cm^?1 for II; characteristic peaks of N? H stretch vibration appeared at 1570 cm^?1 in II. The X‐ray diffraction analysis showed that the peaks at 2θ = 10° and 28° disappeared in chitosan derivatives I and III, respectively; the peak at 2θ = 10° disappeared and the peak at 2θ = 28° decreased in chitosan‐crown ether II; and the peak at 2θ = 20° decreased in all chitosan derivatives. In the solid‐state ¹³C NMR, characteristic aromatic carbon appeared at 129 ppm in all chitosan derivatives, and the characteristic peaks of carbon in C?N groups appeared at 151 ppm in chitosan crown ethers I and III. The adsorption and selectivity properties of I, II, and III for Pd²⁺, Au³⁺, Pt⁴⁺, Ag⁺, Cu²⁺, and Hg²⁺ were studied. Experimental results showed these adsorbents not only had good adsorption capacities for noble metal ions Pd²⁺, Au³⁺, Pt⁴⁺, and Ag⁺, but also high selectivity for the adsorption of Pd²⁺ with the coexistence of Cu²⁺ and Hg²⁺. Chitosan‐crown ether II only adsorbs Hg²⁺ and does not adsorbs Cu²⁺ in an aqueous system containing Pd²⁺, Cu²⁺, and Hg²⁺. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 83: 1886–1891, 2002