Chitosan Derivatives: Introducing New Functionalities with a Controlled Molecular Architecture for Innovative Materials.

The functionalization of polymeric substances is of great interest for the development of innovative materials for advanced applications. For many decades, the functionalization of chitosan has been a convenient way to improve its properties with the aim of preparing new materials with specialized characteristics. In the present review, we summarize the latest methods for the modification and derivatization of chitin and chitosan under experimental conditions, which allow a control over the macromolecular architecture. This is because an understanding of the interdependence between chemical structure and properties is an important condition for proposing innovative materials. New advances in methods and strategies of functionalization such as the click chemistry approach, grafting onto copolymerization, coupling with cyclodextrins, and reactions in ionic liquids are discussed.

Effect of the molecular architecture on the thermosensitive properties of chitosan-g-poly(N-vinylcaprolactam).

A series of thermoresponsive copolymers based on chitosan-g-poly(N-vinylcaprolactam) were synthesized by amidation reaction using 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride as coupling reagent. The effect of molecular architecture on the thermoresponsive properties of the graft copolymers solutions was studied by varying the chain length of the grafted poly(N-vinylcaprolactam), PVCL, (in the range from 4 to 26 kDa) and the spacing between grafted chains onto the chitosan backbone. The most interesting characteristic of these copolymers is their solubility in water at temperatures below their lower critical solution temperature (LCST). These solutions presented a LCST between 36 and 44 °C, which decreases with the spacing and length of grafted PVCL chains onto the chitosan backbone, in contrast with the limited decrease of the LCST of PVCL above a critical M¯n value around 18 kDa. This behavior offers tangible possibilities for the preparation and application of sensitive bioactive formulations and "smart" drug delivery systems.

N-(furfural) chitosan hydrogels based on Diels-Alder cycloadditions and application as microspheres for controlled drug release.

In this study, chitosan was chemically modified by reductive amination in a two-step process. The synthesis of N-(furfural) chitosan (FC) was confirmed by FT-IR and (1)H NMR analysis, and the degrees of substitution were estimated as 8.3 and 23.8%. The cross-linkable system of bismaleimide (BM) and FC shows that FC shared properties of furan-maleimide chemistry. This system produced non-reversible hydrogel networks by Diels-Alder cycloadditions at 85 °C. The system composed of BM and FC (23.8% substitution) generated stronger hydrogel networks than those of FC with an 8.3% degree of substitution. Moreover, the FC-BM system was able to produce hydrogel microspheres. Environmental scanning electron microscopy revealed the surface of the microspheres to be non-porous with small protuberances. In water, the microspheres swelled, increasing their volume by 30%. Finally, microspheres loaded with methylene blue were able to release the dye gradually, obeying second-order kinetics for times less than 600 min. This behavior suggests that diffusion is governed by the relaxation of polymer chains in the swelled state, thus facilitating drug release outside the microspheres.

Physical properties and antibacterial activity of chitosan/acemannan mixed systems.

The aim of the present study was to investigate the mechanical and thermal properties of mixed chitosan-acemannan (CS-AC) mixed gels and the antibacterial activity of dilute mixed solutions of both polysaccharides. Physical hydrogels of chitosan comprising varying amounts of non-gelling acemannan were prepared by controlled neutralization of chitosan using ammonia. As the overall acemannan concentration in the mixed hydrogel increased while fixing that of CS, the mechanical strength decreased. These results indicate that AC perturbs the formation of elastic junctions and overall connectivity as it occurs in the isolated CS network. Heterotypic associations between CS and AC leading to the formation of more compact microdomains may be at play in reducing the density of the gel network consolidated by CS, possibly due to shorter gel junctions. Micro-DSC studies at pH 12.0 seem consistent with the suggestion that molecular heterotypic associations between CS and AC may be at play in determining the overall physical properties of the mixed gel systems. In dilute solution, CS showed antimicrobial activity against Staphylococcus aureus but not against Escherichia coli; AC did not exert antimicrobial activity against any of the two bacterial species. In blended solutions of both polysaccharides, as the amount of AC increased, the antimicrobial activity of the system against S. aureus ceased. In conclusion, this study demonstrates that it is feasible to incorporate acemannan in chitosan-acemannan gels and that although the mechanical strength decreases due to the presence of AC, the gel network persists even at high amount of AC. This study anticipates that the CS-AC mixed gels may offer promise for the future development of biomaterials such as scaffolds to be used in wound therapy.

Thermoresponsive behavior of chitosan-g-N-isopropylacrylamide copolymer solutions.

Chitosan-g-N-isopropylacrylamide (NIPAm) water-soluble copolymers were synthesized and characterized by FTIR and (1)H NMR spectroscopies combined with conductometric and potentiometric titrations. Their thermoresponsive, fully reversible, behavior in aqueous solutions was characterized by means of microcalorimetry and rheology. During heating of copolymer solutions there is a well-known endothermic effect, which coincides with a marked increase in G' and a moderate decrement in G'' due to the formation of a hydrophobic network at the expense of the net amount of sol fraction. It was also found that a straight dependence between the values of G' above the LCST and the enthalpies associated with the transition reflecting that the connectivity in the gel network is governed by the net number of formed enthalpic-hydrophobic driven-junctions. Both the LCST and the enthalpy change vary with the ionic strength of copolymer solutions, but no dependence was found with the neutralization of the polyelectrolyte chain.

Molecularly imprinted chitosan-genipin hydrogels with recognition capacity toward o-xylene.

A molecularly imprinted material was developed from hydrogels of chitosan (CS) cross-linked with genipin (GNP) using o-xylene as the template molecule. Gelling time, mechanical, and diffusion properties of CS-GNP hydrogels were initially investigated to establish optimal conditions to prepare molecularly imprinted hydrogels (MIHs). The elastic modulus was found to be directly proportional to the degree of cross-linking (R = moles of genipin/moles of glucosamine) while the diffusion of water, as monitored by magnetic resonance imaging, decreased with R. CS-GNP hydrogels of varying R were imprinted with o-xylene (MIH(o-xylene)). The adsorption capacity of o-xylene by MIH(o-xylene) was greater than the corresponding control hydrogels, particularly at R = 0.25. Freundlich isotherms yielded a better fitness than Langmuir ones and afforded n and Q(max)values of 2.55 and 103.3 mg/g, respectively. The imprinted hydrogel showed the highest adsorption capacity for o-xylene; however, the material was not highly selective as it also exhibited the capacity to adsorb m- and p-xylene isomers. In turn, the MIH(o-xylene) showed a low adsorption when 2-fluorotoluene was used in rebinding experiments, suggesting that molecular recognition by the binding sites is influenced by the electronic and steric properties of the analyte molecule, thus effectively confirming the imprinting effect within the MIH(o-xylene) network. This work opens the possibility to future development of materials with the capacity to adsorb o-xylene analogue molecules such as contaminants bearing chlorinated aromatic structures.

Determination of chitin and protein contents during the isolation of chitin from shrimp waste.

Accurate determination of chitin and protein contents in crustacean biomass and the intermediate products during the industrial isolation of chitin cannot be made directly from the total nitrogen content, unless the appropriate corrections are applied. This method, however, is affected by the presence of other nitrogen-containing chemical species that are formed endogenously or by the action of microorganisms during the handling of the sample. Therefore, an alternative rapid method to estimate the contents of these components can be very useful both in research and in various fields of application. An original method has been developed to address this problem. The method consists of the development of a set of equations based on the stoichiometric contents of nitrogen of chitin and protein whereby the amounts of each component can be estimated from the value of the total nitrogen content, provided the rest of the proximate composition of the sample is accurately known. In order to validate the procedure, a set of model mixtures of pure chitin and protein concentrate in the solid state, both extracted from shrimp head waste, are used. Excellent agreement between the predicted and real values of chitin and protein are obtained (R2=0.98, slope=0.90). When the proposed method is tested in the analysis of real samples obtained from five different processing protocols of pretreatment of raw shrimp head, it is found that in general the values of protein and chitin contents throughout the various stages of the process vary as expected. [GRAPH: SEE TEXT] Variation of the measured total nitrogen versus calculated stoichiometric total nitrogen of the chitin-protein mixtures.

Kinetics of gelation and thermal sensitivity of N-isobutyryl chitosan hydrogels.

N-Acylation of chitosan with carboxylic anhydrides in dilute acetic acid/methanol has been a well documented strategy to selectively modify chitosan. Although this reaction is known to lead to irreversible gel formation, the kinetics and mechanism of this process have not so far been addressed. To this purpose, gel formation during the N-isobutyrylation of chitosan was investigated as a function of the reaction stoichiometry (R), chitosan concentration, and temperature by small deformation oscillatory rheology. Gel formation follows closely the chemical reaction and it proceeds predominantly under second-order kinetics as established from the dependence of critical gel time, t(gel), on R and concentration. The activation energy value derived from t(gel) vs 1/T data (E(a) = 68.29 +/- 1.80 kJ/mol) was almost identical to values reported for the chitosan N-acetylation reaction in previous studies. An excess isobutyric anhydride is suggested to be necessary for nucleation and hydrophobic association. The potential application of N-isobutyrylchitosan (NIBC) hydrogels in the design of thermally sensitive materials is also demonstrated.