Synthesis and characterization of a novel chitosan‐based network prepared using naturally occurring crosslinker

Novel chitosan‐based polymeric networks were synthesized and characterized by FTIR, UV and C¹³ NMR. A naturally occurring crosslinking reagent—genipin, which has been used in herbal medicine and in the fabrication of food dyes, was used to prepare crosslinked chitosan hydrogel. The heterocyclic compound of genipin crosslinked chitosan was formed by a nucleophilic attack by amino group on the olefinic carbon atom at C‐3 of deoxyloganin aglycone, followed by opening of the dihydropyran ring and attack by the secondary amine group on the intermediate aldehyde group. Additional, secondary amide linkages could be established in the genipin crosslinked chitosan network by the reaction of ester group of genipin with amino group of chitosan. This bifunctional linkages of genipin with amino group of chitosan leads to form crosslinked networks. Genipin reacted with nucleophilic reagent such as chitosan could further go through a polymerization to form oligomer‐bridge in the crosslinked network. The finally formed chitosan networks are blue color, elastic and exhibits pH‐dependent swelling characteristics. The swelling ratio of the chitosan hydrogel increased at pH lower than 3 and higher than 11 due to the hydrolysis of amide linkage in the genipin crosslinked chitosan network by acid or alkaline, followed by the protonation of amine group or ionization of carboxyl acid group in the network. © 2000 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 38: 2804–2814, 2000     

Mechanism and kinetics of the crosslinking reaction between biopolymers containing primary amine groups and genipin

The reaction mechanism of chitosan, bovine serum albumin (BSA), and gelatin with genipin (a natural crosslinking reagent) was examined with infrared, ultraviolet–visible, and ¹³C NMR spectroscopies; protein‐transfer reaction mass spectrometry; photon correlation spectroscopy; and dynamic oscillatory rheometry. Two reactions that proceeded at different rates led to the formation of crosslinks between primary amine groups. The fastest reaction to occur was a nucleophilic attack on genipin by a primary amine group that led to the formation of a heterocyclic compound of genipin linked to the glucosamine residue in chitosan and the basic residues in BSA and gelatin. The second, slower, reaction was the nucleophilic substitution of the ester group possessed by genipin to form a secondary amide link with chitosan, BSA, or gelatin. A decreased crosslinking rate in the presence of deuterium oxide rather than water suggested that acid catalysis was necessary for one or both of the reactions to proceed. The behavior of the gel time with polymer concentration was consistent with second‐order gelation kinetics resulting from an irreversible crosslinking process, but was complicated by the oxygen radical‐induced polymerization of genipin that caused the gels to assume a blue color in the presence of air. The lower elastic modulus attained after a given time during crosslinking of the globular protein BSA as compared to the coiled protein gelatin, despite possessing more crosslinkable basic residues, demonstrated the importance of protein secondary and tertiary structures in determining the availability of sites for crosslinking with genipin in protein systems. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 3941–3953, 2003     

Star‐shaped and photocrosslinked poly(1,5‐dioxepan‐2‐one): Synthesis and characterization

New star‐shaped and photocrosslinked poly(1,5‐dioxepan‐2‐one) (PDXO) has been synthesized through ring‐opening polymerization initiated by SnOct₂/pentaerythritol. The star‐shaped PDXO was end‐functionalized by acrolyol chloride to form acrylate end groups. The end‐functionalized PDXO was photocrosslinked initiated by 2,2‐dimethoxy‐2‐phenylacetophenone. The gel content ranged from 80 to 99%, indicating a high degree of crosslinking. The thermal properties of the star‐shaped PDXO and the photocrosslinked PDXO were analyzed by differential scanning calorimetry. The glass‐transition temperature was determined to approximately ?32 °C for the crosslinked PDXO. The viscosity numbers were determined for star‐shaped PDXO, with reference to linear homologues. The star‐shaped PDXO had lower viscosity numbers than the linear counterparts. The crosslinked PDXO showed a rather hydrophilic surface as compared with other resorbable polyesters. The advancing contact angle was 64 ± 2, and the receding angle was 57 ± 4. © 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 40: 2049–2054, 2002     

Synthesis,swelling properties,and network structure of new stimuli‐responsive poly(N‐acryloyl‐N′‐ethyl piperazine‐co‐N‐isopropylacrylamide) hydrogels

Poly(N‐acryloyl‐N′‐ethyl piperazine‐co‐N‐isopropylacrylamide) hydrogels were prepared by thermal free‐radical copolymerization of N‐acryloyl‐N′‐ethyl piperazine (AcrNEP) and N‐isopropylacrylamide (NIPAM) in solution using N, N′‐methylene bisacrylamide as the crosslinking agent. The gels were responsive to changes in external stimuli such as pH and temperature. The pH and temperature responsive character of the gels was greatly dependent on the monomer content, namely AcrNEP and NIPAM, respectively. The gels swelled in acidic (pH 2) and de‐swelled in basic (pH 10) solutions with a response time of 60 min. With increase in temperature from 23 to 80 °C the swelling of the gels decreased continuously and this effect was different in acidic and basic solutions. The temperature dependence of equilibrium water content of the gels was evaluated by the Gibbs–Helmholtz equation. Detailed analysis of the swelling properties of these new gels in relation to molecular heterogeneity in acidic (pH 2) and basic (pH 10) solutions were performed. Water transport property of the gels was studied gravimetrically. In acidic solution, the diffusion process was non‐Fickian (anomalous) while in basic solution, the diffusion was quasi‐Fickian. The effect was more evident in solution of pH 2 than in pH 10. Various structural parameters of the gels such as number‐average molar mass between crosslink (M_c), the crosslink density (ρ_c), and the mesh size (ξ) were evaluated. The mesh sizes of the hydrogels were between 64 and 783 Å in the swollen state in acidic solution and 20 and 195 Å in the collapsed state in basic solution. The mesh size increased between three to four times during the pH‐dependent swelling process. The amount of unbound water (free water) and bound water of the gels was also evaluated using differential scanning calorimetry. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Synthesis and characterization of polyhedral oligomeric silsesquioxane hybrid co‐crosslinked poly(N‐isopropylacrylamide‐co‐dimethylaminoethyl methacrylate) hydrogels

Polyhedral oligomeric silsesquioxane hybrid temperature and pH double‐responsive hydrogels with organic–inorganic co‐crosslinked networks are synthesized by in situ, free‐radical polymerization of N‐isopropylacrylamide and dimethylaminoethyl methacrylate in the presence of both organic crosslinker N,N′‐methylenebis(acrylamide) (BIS) and inorganic crosslinker octavinyl polyhedral oligomeric silsesquioxane (OvPOSS) in tetrahydrofuran media. The resulting hydrogels (OR‐OvP gels) display obvious temperature and pH double responsiveness, OvPOSS particles dispersed in polymer make a dominant effect on the properties of gels. With the increase of OvPOSS, the aggregation of particles on nano‐ or microscale happens and causes a considerable change on the properties of gels, such as the lower critical solution temperature and better compression strength. Specially, the interconnected microporous structure of gels ascribed to the microphase separation results in faster deswelling rate, which makes the gel become attractive. Besides, the crosslink by BIS intensifies the heterogeneity of gels significantly, which could also be used to adjust the properties of gels. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2013 , 51, 1494–1504     

Grignard condensation routes to 1,3‐disilacyclobutane‐containing cyclolinear polycarbosilanes

Alkylene‐ and arylene‐bridged cyclolinear polycarbosilanes (CLPCS) with 1,3‐disilacyclobutane (DSCB) rings incorporated in the main chain of the polymer were prepared by polycondensation between corresponding di‐functional DSCB derivatives and di‐Grignard reagents. Well‐defined, low molecular weight (M_n = 3–5K; DP = 17–26), hexylene‐ and phenylene‐bridged CLPCS polymers were obtained without appreciable ring opening of the DSCB rings. Large exothermic peaks were observed in the DSC for these CLPCSs, which indicated, along with the IR spectra, that crosslinking occurred on heating to about 250 °C via the ring opening of the embedded, alternating, DSCB rings. Moreover, PB‐CLPCS undergoes photochemically induced crosslinking on UV irradiation to form crosslinked polycarbosilane network films. The spin‐cast, cured, films of these CLPCSs exhibit relatively low dielectric constants and promising thermal and mechanical properties for applications in electronics, for example, directly UV‐photoimprinted low‐k dielectrics. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017 , 55, 1547–1557     

Crosslinking of vinyl‐terminated biphenyl and naphthalene side‐chain liquid‐crystalline poly(epichlorohydrin) derivatives

We performed the crosslinking of vinyl‐terminated biphenyl and naphthalene side‐chain liquid‐crystalline polyethers using peroxide‐type initiators with and without the addition of tertiary amine promoters. The crosslinking temperatures were chosen in the range of mesophase stability to allow the mesophase order to be frozen. The biphenyl derivatives, with a high isotropization temperature, were crosslinked to a large extent. This led to anisotropic thermosets. To crosslink naphthalene derivatives, amine promoters were needed, but degrees of crosslinking were lower, and anisotropic elastomers were obtained. Crosslinking processes were studied by differential scanning calorimetry, polarized optical microscopy, and Fourier transform infrared spectroscopy. The nature of the frozen mesophase was confirmed by X‐ray diffraction studies on mechanically oriented samples. © 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 40: 2237–2244, 2002     

Kinetic study of chitosan‐tripolyphosphate complex reaction and acid‐resistive properties of the chitosan‐tripolyphosphate gel beads prepared by in‐liquid curing method

Chitosan gel beads were prepared using an in‐liquid curing method by the ionotropic crosslinking with sodium tripolyphosphate. Crosslinking characteristics of the chitosan‐TPP beads were improved by the modification of in‐liquid curing mechanism of the beads in TPP solution. Chitosan gel beads cured in pH value lower than 6 were really ionic‐crosslinking controlled, whereas chitosan gel beads cured in pH values higher than 7 were coacervation‐phase inversion controlled accompanied with slightly ionic‐crosslinking dependence. According to the result, significantly increasing the ionic‐crosslinking density of chitosan beads could be achieved by transferring the pH value of the curing agent, TPP, from basic to acidic. The swelling behavior of various chitosan beads in acid appeared to depend on the ionic‐crosslinking density of the chitosan‐TPP beads that were deeply affected by the curing mechanism of the beads. The mechanism of chitosan‐TPP beads swollen in weak acid was chain‐relaxation controlled, while the mechanism of chitosan‐TPP beads swollen in strong acid seem to be not only chain‐relaxation but also chain‐scission controlled. Chitosan‐TPP beads prepared in acidic TPP solution decreased the chain‐scission ability due to the increase of ionic crosslinking density of the beads. By the transition of curing mechanism, the swelling degree of chitosan‐TPP beads was depressed, and the disintegration of chitosan‐TPP beads would not occur in strong acid. The mechanism of ionic‐crosslinking reaction of chitosan beads could be investigated by an unreacted core model, and the curing mechanism of the chitosan beads is mainly diffusion controlled when higher than 5% of chitosan was employed. © 1999 John Wiley & Sons, Inc. J Polym Sci B: Polym Phys 37: 1551–1564, 1999     

Bioreducible and core‐crosslinked hybrid micelles from trimethoxysilyl‐ended poly(ε‐caprolactone)‐S‐S‐poly(ethylene oxide) block copolymers: Thiol‐ene click synthesis and properties

Bioreducible and core‐crosslinked hybrid micelles were for the first time fabricated from biodegradable and biocompatible trimethoxysilyl‐terminated and disulfide‐bond‐linked block copolymers poly(ε‐caprolactone)‐S‐S‐poly(ethylene oxide), which were prepared by combining thiol‐ene coupling reaction and ring‐opening polymerization. The molecular structures, physicochemical, self‐assembly, and bioreducible properties of these copolymers were thoroughly characterized by means of FTIR, ¹H NMR, gel permeation chromatography, differential scanning calorimetry, wide‐angle X‐ray diffraction, dynamic light scattering (DLS), and transmission electron microscopy. The core‐crosslinking sol‐gel reaction was confirmed by ¹H NMR, and the core‐crosslinked hybrid micelles contained about 3 wt % of silica. The bioreducible property of both uncrosslinked and core‐crosslinked micelles in 10 mM 1,4‐dithiothreitol (DTT) solution was monitored by DLS, which demonstrated that the PEO corona gradually shedded from the PCL core. The anticancer doxorubicin drug‐loaded micelles showed nearly spherical morphology compared with blank micelles, presenting a DTT reduction‐triggered drug‐release profile at 37 °C. Notably, the core‐crosslinked hybrid micelles showed about twofold drug loading capacities and a half drug‐release rate compared with the uncross‐liked counterparts. This work provides a useful platform for the fabrication of bioreducible and core‐crosslinked hybrid micelles potential for anticancer drug delivery system. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Synthesis and Properties of Hydrogels Based on Chitosan and Poly(Vinyl Alcohol) Crosslinked by Genipin

Semi‐interpenetrating polymeric networks of chitosan and poly(vinyl alcohol) [PVA] were prepared by varying the ratio of the constituents. The hydrogels were crosslinked using genipin, a naturally occurring nontoxic cross‐linking agent. The swelling behavior of these hydrogels was studied by immersing the films in deionized water at various temperatures and in buffer solutions of different pH. The states of water in the hydrogels, swollen at 25°C and pH 7, were determined using Differential Scanning Calorimetry (DSC). The swelling behavior of the gels was found to be dependent on temperature and pH of the medium. The amount of freezing water in the swollen hydrogels increased, whereas the amount of nonfreezing bound water remained more or less the same with increasing PVA concentration.     

UV‐induced crosslinking of ring opening metathesis block copolymer micelles

Statistical and amphiphilic block copolymers bearing cinnamoyl groups were prepared by ring opening metathesis polymerization (ROMP). The UV‐induced [2 + 2] cycloaddition reaction of polymer bound cinnamic acid groups was studied in polymer thin films as well as in block copolymer micelles. In both cases, exposure to UV‐light for 10 min led to a crosslinking conversion of about 60%, as determined by FT‐IR spectroscopy and UV–vis absorption measurements. Time based IR‐spectroscopy revealed a maximum conversion of 78% reached after an irradiation time of about 16 min. For micelles obtained from polymers bearing 5 mol % or more cinnamoyl groups, the crosslinking reaction proceeded smoothly, yielding in crosslinked particles which were stable in a non‐selective solvent (CHCl₃). Diameters determined by dynamic light scattering in the selective solvent (MeOH) were similar for both, non‐crosslinked and crosslinked micelles, whereas diameters of crosslinked micelles in the non‐selective solvent (CHCl₃) were significantly larger compared to MeOH samples. This strategy of direct self assembly of block‐copolymers in a selective solvent followed by “clean” crosslinking, without the need for additional crosslinking reagents or crosslinking initiators, provides a straight forward approach toward ROMP‐based polymeric nano‐particles. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 2402–2413, 2008     

Gelating polypeptide matrices based on the difunctional N‐carboxyanhydride diaminopimelic acid cross‐linker

This work reports the synthesis of a new difunctional N‐carboxyanhydride (NCA) monomer, namely diaminopimelic acid (DAP), and its use in the one‐pot preparation of an organogelating copolypeptide. The organogel is formed in situ through ring‐opening polymerization (ROP) of DAP NCA from helical poly(ε‐carbobenzyloxy‐L‐lysine) (PZLL) blocks in a mixture of dimethylformamide/chloroform. Gelation occurs by immobilizing the solvent through core crosslinking and is stabilized through physical intermolecular conformations. After removal of the carbobenzyloxy (cbz or Z) protecting groups, the network remains intact in exceedingly high aqueous concentrations (99.5%). FTIR is used to characterize the secondary structure, revealing the conformational arrangements that contributed to these stabilized gel networks with their relative mechanical properties determined via real‐time rheological assays. DAP core crosslink of the random coil forming polypeptoid poly(sarcosine) (PSar) is also resulting in networks but is devoid of any stabilized physical interactions, thus yielding significantly weaker gels as a result. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019     

Preparation and sorption properties of a β‐cyclodextrin‐linked chitosan derivative

β‐Cyclodextrin (β‐CD) was coupled to chitosan by the intermediate of its monochlorotriazinyl derivative, called βW7MCT, so that a chitosan derivative bearing cyclodextrin was obtained. Because the average degree of substitution of the cyclodextrin derivative was 2.8, the reaction yielded crosslinked insoluble products. The structure of these materials has been investigated by high‐resolution magic‐angle spinning (HRMAS) with gradients. For the first time, HRMAS spectra of chitosan polymers containing β‐CD were obtained. This NMR technique produced one‐ and two‐dimensional well‐resolved solid‐state spectra. These data confirm the proposed structure. Decontamination of waters containing textile dyes were carried out with the crosslinked derivatives. These tests showed that the new chitosan derivatives are characterized by a rate of sorption and a global efficiency superior to that of the parent chitosan polymer and of the well‐known cyclodextrin‐epichlorohydrin gels. © 2000 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 39: 169–176, 2001     

Effect of Chemical Crosslinking on the Swelling and Shrinking Properties of Thermal and pH‐Responsive Chitosan Hydrogels

The ability to form a gel through the physical or chemical crosslinking of chitosan has been well documented. In an attempt to mimic biological systems, thermal and pH‐sensitive chitosan cylindrical hydrogels were produced by a combination of physical and chemical crosslinking processes. To this end, chitosan hydrogels prepared from alkali chitin were molded in cylinders and, once washed, were further crosslinked with glutaraldehyde at stoichiometric ratios, R (= [? CH?O]/[? NH₂]), of 1.61 and 3.22 × 10^?2. Variation in swelling as a result of stepwise changes in temperature between 40 and 2 °C at pH values of 7.0, 7.6, and 8.0 revealed that the system responds in markedly different manners dependent upon the pH. At pH 7.0, cooling from 40 to 2 °C results in contraction of the gel network structure. While raising the temperature from 2 to 40 °C leads to a rapid swelling response (i.e., ca. a twofold increase in the amount of solvent uptake). Subsequent cooling to 2 °C is accompanied by a new contraction cycle. At pH ≥ 7.6 the temperature dependence of the swelling–contraction behavior is exactly the opposite of that observed at pH 7.0. Very similar trends were observed for the gels at both degrees of crosslinking. The swelling–shrinking behavior observed in gels of pH ≥ 7.6, is similar in kind to that of uncrosslinked gels and is interpreted in terms of a lower critical solution temperature (LCST) volume phase transition, driven by hydrophobic association, presumably involving residual acetyl groups in the chitin. The results at pH 7.0 suggest that the slight ionization of the ? NH groups leads to destruction of the hydrophobic hydration thus effectively reversing the negative thermal shrinking.

Evolution of the swelling ratio, S, as a function of time and temperature for crosslinked chitosan hydrogels. Circles represent S values recorded at pH 7.0 and triangles those at pH 7.6.     

Fabrication,chemical modification,and topographical patterning of reactive gels assembled from azlactone‐functionalized polymers and a diamine

The work reported here demonstrates an approach to the fabrication of chemically reactive and topographically patterned hydrogels using the azlactone‐functionalized polymer poly(2‐vinyl‐4,4'‐dimethylazlactone) (PVDMA) and the hydrophilic diamine Jeffamine®. Gels were initially assembled in DMSO but can be subsequently transferred into aqueous media to form hydrogels. Spectroscopic characterization of assembled gels demonstrated that variation in the stoichiometric ratio of azlactones to amines during gel synthesis permits control over the extent of crosslinking in the gels. Residual azlactones not consumed during crosslinking can be exploited to further functionalize these gels with hydrophobic, hydrophilic, and macromolecular amines that influence the physicochemical properties of these materials in aqueous solvents. The surface and bulk of these gels can be differentially functionalized (i.e., different functional groups on the gel surface relative to the bulk) by taking advantage of different rates of diffusion of macromolecular amines versus small molecule amines into assembled gels. Finally, these azlactone‐functionalized gels can be topographically patterned with microwell arrays using a replica molding technique and chemically modified postfabrication with amine nucleophiles. This reactive approach to the fabrication of topographically patterned and chemically functionalized hydrogels offers a straightforward method for the rapid synthesis of micropatterned scaffolds of interest in a broad range of applications. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017 , 55, 3185–3194     

A facile and controllable synthesis of dual‐crosslinked elastomers based on linear bifunctional polydimethylsiloxane oligomers

Dual‐crosslinked supramolecular elastomers with the hybrid network consisting of hydrogen bonds and covalent bonds combine the reversibility of hydrogen bond and mechanical properties of covalent crosslinking network. In this article, isocyanate mixture is used as curing agent to prepare dual‐crosslinked elastomer based on bifunctional polydimethylsiloxane under mild condition. This method can effectively build up a hybrid network with the designed structure. A series of elastomers with same hydrogen bond density and variable covalent crosslinking degree are obtained. Swelling measurements and ¹H‐NMR spectra confirm the feasibility and controllability of curing method, the increasing of bifunctional isocyanate give rise to higher covalent crosslinking degree, improving the solvent resistance. The studies on viscoelastic property show that the introduction of an irreversible covalent crosslinking network stabilize the hybrid network, restrain the chain movement. The mechanical and self‐healing property studies reveal that the covalent crosslink significantly reinforce the whole network, while the reparable strength seems to mainly depend on the hydrogen bond density. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 3760–3768     

A new oxidation state of aniline pentamer observed in water‐soluble electroactive oligoaniline‐chitosan polymer

A novel water‐soluble electroactive polymer, aniline pentamer crosslinked chitosan (Pentamer‐c‐Chi), was prepared by condensation polymerization of the terminal carboxyl groups in aniline pentamer with the amino side groups in chitosan in aqueous solution. The carboxyl groups were activated by N‐hydroxysuccinimide (NHS) and N,N′‐dicyclohexylcarbodiimide (DCC). The electrochemical behavior of anilinepentamer in this kind of crosslinked polymer was studied in acidic aqueous solution by means of cyclic voltammetry (CV), UV–vis, and electron spin resonance (ESR) spectroscopy. There were three reversible redox peaks in the CV of Pentamer‐c‐Chi. A new emeraldine oxidization state in the form of radical cations was proposed, which was associated with the new absorption band at 370 nm in the UV–vis spectra. The ESR of the aqueous solution of Pentamer‐c‐Chi showed a single Lorentzian shaped signal, which suggested the existence of radical cations. The new redox state was pH dependent and appeared only at pH < 3. The stability of radical cations could be attributed to the hydrogen bonds between radical cations, water, and chitosan. Morphological structure of the Pentamer‐c‐Chi can be adjusted by varying the content of aniline pentamer. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 1124–1135, 2008     

Synthesis of siloxane‐crosslinked polysilylenemethylenes by chlorodephenylation

Thermally stable polysilylenemethylenes (PSMs) with siloxane crosslinking moieties were successfully synthesized by chlorodephenylation of preformed poly(methylphenylsilylenemethylene) (PMPSM) and subsequent in situ alcoholysis/hydrolysis/condensation reactions. The simplified process and mild reaction conditions are quite advantageous. The crosslink density of these materials can be adjusted by the degree of chlorodephenylation, although an alkoxysilyl group remains to some extent. The resulting crosslinked PSMs have well defined structures in which the backbone is composed of MePhSiCH₂ and Me(MeO)SiCH₂ as well as Me(O_1/2)SiCH₂ as a crosslinking moiety. The resulting crosslinked PSMs exhibited glass‐transition temperatures ranging from 15 to 20 °C, whereas that of linear PMPSM was 22 °C. The crosslinked PSMs remained unchanged in weight below 300 °C, suggesting that they are thermally stable up to that temperature. The good solvent resistance caused by crosslinking as well as high thermal stability of these materials allow us to design new PSM‐based polymer blends and preceramic polymers. © 2001 John Wiley & Sons, Inc. J Polym Sci Part A: Polym Chem 40: 416–422, 2002     

Morphology and temperature responsiveness–swelling relationship of poly(N‐isopropylamide–chitosan) copolymers and their application to drug release

Poly [N‐isopropylacrylamide (NIPAAm)–chitosan] crosslinked copolymer particles were synthesized by soapless emulsion copolymerization of NIPAAm and chitosan. An anionic initiator [ammonium persulfate (APS)] and a cationic initiator [2,2′‐azobis(2‐methylpropionamidine)dihydrochloride (AIBA)] were used to initiate the reaction of copolymerization. The chitosan–NIPAAm copolymer synthesized by using APS as the initiator showed a homogeneous morphology and exhibited the characteristic of a lower critical solution temperature (LCST). The copolymer synthesized by using AIBA as an initiator showed a core–shell morphology, and the characteristic of LCST was insignificant. The LCST of the chitosan–NIPAAm copolymer depended on the morphology of the copolymer particles. In addition, the chitosan–NIPAAm copolymer particles were processed to form copolymer disks. Then, the effect of various variables such as the chitosan/NIPAAm weight ratio, the concentration of crosslinking agent, and the pH values on the swelling ratio of chitosan–NIPAAm copolymer disks were investigated. Furthermore, caffeine was used as the model drug to study the characteristics of drug loading of the chitosan–NIPAAm copolymer disks. Variables such as the chitosan/NIPAAm weight ratio and the concentration of the crosslinking agent significantly influenced the behavior of caffeine loading. Two factors (pore size and swelling ratio) affected the behavior of caffeine release from the chitosan–NIPAAm copolymer disks. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 3029–3037, 2004     

Kinetic analysis of genipin degradation in aqueous solution

Degradation of genipin (GP), a low toxicity natural protein crosslinking agent, in aqueous solution was monitored by HPLC at various pH levels. Degradation of GP was consistent with a mechanism consisting of a first order reaction with a reversible first step. Formation of the intermediate was slowest at more neutral pHs while formation of the irreversible product was correlated to increasing alkalinity. Degradation at all pHs was enhanced by the presence of phosphate ions. Degradation of GP most likely proceeds via the reversible opening of the dihydropyran ring by water followed by irreversible polymerization of the intermediate. Degraded solutions containing no detectable GP or intermediate, however, are still capable of crosslinking proteins.