Search

The samples of poly(

A new synthesis method was developed and optimized by a full factorial design for conjugating hydroxycinnamic acids (HCA-s) to chitosan. Cinnamic acid and tert-butyldimethylsilyl protected HCA-s were converted to their corresponding acyl chlorides and reacted with 3,6-di-O-tert-butyldimethylsilyl-chitosan to selectively form amide linkages, resulting in water-soluble conjugates after deprotection. Nineteen conjugates were obtained with various degrees of substitution (DS) ranging from 3% to 60%. The conjugates were found to be bactericidal against Staphylococcus aureus and Escherichia coli, with their activities equal to chitosan at low DS but an increase in the DS correlated with reduced activity. DPPH (2,2-diphenyl-1-picrylhydrazyl) scavenging assay was performed to determine the EC50 values. Chitosan only exhibited low antioxidant activity, whereas the HCAchitosan conjugates exhibited higher antioxidant activities correlating with the DS. One caffeic acid conjugate (21%) was 4000 times more active than chitosan and more active than free caffeic acid., The research work was funded by the Icelandic Research Fund (Rannis Grant No. 185188-053) and by a doctoral grant from the University of Iceland research fund., Pre-print (óritrýnt handrit)

We have studied the effect of chitosan sponges, produced from chitosan batches with distinct degree of deacetylation (DDA) and molecular weight (Mw), on the adhesion, growth and differentiation of primary human osteoblasts with an aim to offer a suitable tool for guided bone regeneration. All the chitosan sponges revealed similar microstructure, irrespective of the DDA (58, 73, 82, 88, and 91 %) and Mw (749, 547, 263, 215, and 170 kDa, respectively). Cell spreading was higher on sponges having a higher DDA. Higher DDA induced a more pronounced increase in alkaline phosphatase activity, osteopontin (OPN), vascular endothelial growth factor-A (VEGF), interleukin-6 (IL-6), and reduction in monocyte chemoattractant protein-1 (MCP-1), sclerostin (SOST) and dickkopf related protein-1 as compared to lower DDA. Lower DDA induced the increased secretion of osteoprotegerin and SOST as compared to higher DDA. The combination of higher DDA and Mw induced an increased secretion of VEGF and IL-6, however reduced the secretion of OPN as compared to chitosan with similar DDA but with lower Mw. In summary, the variations in cellular responses to the different chitosan sponges indicate a potential for individual tailoring of desired responses in guided bone regeneration.

Publisher's version (útgefin grein), In this study we have developed biodegradable polymeric nanoparticles (NPs) containing the cytostatic drugs mertansine (MRT) or cabazitaxel (CBZ). The NPs are based on chitosan (CS) conjugate polymers synthesized with different amounts of the photosensitizer tetraphenylchlorin (TPC). These TPC-CS NPs have high loading capacity and strong drug retention due to π-πstacking interactions between the drugs and the aromatic photosensitizer groups of the polymers. CS polymers with 10% of the side chains containing TPC were found to be optimal in terms of drug loading capacity and NP stability. The TPC-CS NPs loaded with MRT or CBZ displayed higher cytotoxicity than the free form of these drugs in the breast cancer cell lines MDA-MB-231 and MDA-MB-468. Furthermore, light-induced photochemical activation of the NPs elicited a strong photodynamic therapy effect on these breast cancer cells. Biodistribution studies in mice showed that most of the TPC-CS NPs accumulated in liver and lungs, but they were also found to be localized in tumors derived from HCT-116 cells. These data suggest that the drug-loaded TPC-CS NPs have a potential in combinatory anticancer therapy and as contrast agents., This work was supported by The Research Council of Norway [NANO2021; Project Number 228200/O70] and The Norwegian Cancer Society. We thank Anne Engen for excellent assistance with cell culturing and Monika Håkerud for professional assistance regarding illumination of cells. We would also like to thank The Norwegian Radium Hospital Research Foundation (RADFORSK) for financial support and The Simon Fougner Hartmann Family Fund for providing means to analytical instrumentation. We also acknowledge a contribution from the University of Iceland Research Fund for the work in Iceland.

This review gives an updated overview of the current state-of-the-art for antimicrobial chitosan and chitosan derivatives and the effects of structural modifications on activity and toxicity. The various synthetic routes introduced for chemical modification of chitosan are discussed, and the most common functional groups are highlighted. Different analytical techniques used for structural characterization of the synthesized chitosan derivatives are discussed and critically evaluated. For the purpose of this review, the antimicrobial chitosan derivatives have been classified on the basis of the type of functional group conjugated to the polymer backbone. In each case, the influence of the degree of substitution on the biological properties has been examined. Finally, we have summarized the collective information and suggested future directions for further research to improve our understanding of the bioactivity and to develop more useful chitosan conjugates.

Publisher's version (útgefin grein), N,N,N-trimethyl chitosan (TMC) with 93% degree of trimethylation was synthesized. TMC and the chitosan starting material were subjected to acidic hydrolysis to produce 49 different samples with a reduced average molecular weight (Mw) ranging from 2 to 144 kDa. This was done to allow the investigation of the relationship between antibacterial activity and Mw over a wide Mw range. NMR investigation showed that hydrolysis did not affect the degree of trimethylation (DSTRI) or the structure of the polymer backbone. The activity of TMC against Staphylococcus aureus (S. aureus) increased sharply with Mw until a certain Mw value (critical Mw for high activity, CMW) was reached. After the CMW, the activity was not affected by a further increase in the Mw. A similar pattern of activity was observed for chitosan. The CMW was determined to be 20 kDa for TMC and 50 kDa for chitosan., This study was initially funded by the Icelandic Research Fund (Grant No. 120443021) and by the EEA Scholarship and Training Fund. The final work was funded by the Icelandic Technical Development fund through the Marine Biotech ERA-NET Project—Blueteeth (Grant No. 179012-0612).

The paper presents a method of depositing N,N,N-trimethyl chitosan (TMC) layers onto polypropylene and polylactide nonwovens. A two-step modification procedure is applied: first, grafting the nonwovens with acrylic acid and next layer-by-layer deposition. Turbidimetric measurements confirm the creation of polycomplexes between grafted poly(acrylic acid) and deposited TMC. The created material structure is evaluated using gravimetric analysis, reflectance Fourier transform infrared spectroscopy, scanning electron microscopy, energy dispersive spectroscopy measurements and pH-metric titration. The modified material exhibits good antibacterial properties against Gram-positive bacteria Staphylococcus aureus.

A series of PEGylated chitosan derivatives were synthesized using protection group strategy. N-mPEG chitosan derivatives were synthesized by two different synthetic routes - either by direct substitution at the amino group or using a spacer with the help of 3,6-O-diTBDMS-protected chitosan as a precursor. The use of TBDMS protection on both the hydroxyl groups of chitosan allowed modification selectively at the amino functionality. N,N,N-trimethyl chitosan (TMC) homopolymer was synthesized and utilized for the 2,2,6,6-Tetramethyl-1-piperidinyloxy (TEMPO) oxidation of the C-6-hydroxyl group. This oxidation step was optimized using various reaction conditions to obtain the 100% oxidized product N,N,N-trimethyl-O-6-carboxy chitosan. The oxidized product was then further used for selective PEGylation at the hydroxyl group of TMC by esterification. Characterization of the synthesized chitosan derivatives was carried out by 1H and COSY NMR and IR spectroscopy.

Experimental design approach was successfully used to guide the synthesis and determine the structure–activity relationship for antimicrobial derivatives of the biopolymer chitosan. Specialized software with D-optimal design capabilities was used to create a library of chitosan derivatives with optimal structural variation in order to conduct a detailed investigation of the structure–activity relationship. The derivatives contain three substituents: N,N,N-trimethylamine, N-acetyl and N-stearoyl at different degrees of substitution (DS) on the 2-amino group of chitosan. The design matrix consisted of 14 target materials that were synthesized in ‘one-pot synthesis’ using TBDMS–chitosan as the precursor to allow precise control of the DS. The antibacterial activity (MIC) towards the Gram positive bacteria Staphylococcus aureus and the Gram negative bacteria Escherichia coli, hemolytic activity (HC50) towards human red blood cells and solubility of the chitosan derivatives were used as the responses in the model. The response surface model was refined by removing the interaction terms to improve the statistical significance and predictive power of the model. The investigation showed that materials with DS for trimethylation in the range 0.45–0.65, acetylation in the range 0.08–0.33 and stearoylation in the range 0.22–0.29 were capable of showing high antimicrobial activity, high solubility and low hemolytic activity.

Three photoactive chitosan derivatives were synthesized using TBDMS chitosan as the starting material. In this study, we also report an optimized method for producing relatively high average molecular weight chitosan precursors for the synthesis of the three N-modified chitosan derivatives having a N-azidobenzoyl group, a N-methacryloyl group and a N-azidobenzoyl-N′,N′,N′-(acetyl-trimethyl ammoniumyl) group. The methacryloyl and azidobenzoyl derivatives synthesized were photografted onto discs of a crosslinked polymethacrylate copolymer used in the industrial production of intraocular lenses (IOLs), with dimensions comparable to those of IOLs. The photografted polymethacrylate was loaded with the antibiotic moxifloxacin, allowing the creation of an antibiotic releasing system that may be further developed for an application in postoperative endophthalmitis prophylaxis.

Bacterial biofilms tolerate extreme levels of antibiotics. Treatment of biofilm infections therefore requires the development of new or modified antimicrobials that can penetrate biofilms and are effective against dormant persistent cells. One such new approach uses the biodegradable biopolymer chitosan and its derivatives as antimicrobials. In this study, we performed synthetic modification of chitosan to selectively introduce different cationic and hydrophobic moieties at varying ratios on chitosan. This improved its aqueous solubility and antimicrobial activity toward bacterial biofilms. Initial evaluation of the chitosan derivatives showed increased activity toward planktonic Staphylococcus aureus. The effect of the quaternary ammoniumyl chitosan derivatives against Staphylococcus aureus biofilms was more variable. The most effective derivatives contained hydrophobic groups, and their efficacy against biofilms depended on the ratio and length of the alkyl chains. Three-dimensional imaging of biofilms confirmed the accessibility and antimicrobial effect of chitosan derivatives with alkyl chains in the full depth of the biofilms.

A new synthetic approach employing two types of protecting groups, tertiarybutyldimethylsilyl (TBDMS) and tertiarybutyloxycarbonyl (Boc) was developed to obtain a series of guanidinylated chitosan derivatives. The synthesis was carried out in organic solvents which allowed quantitative reaction, a good control on the degree of substitution, and 100% substitution of the chitosan amino groups. Similar derivatives carrying the trimethylammonium group were also synthesized as reference compounds. All the derivatives were characterized using 1 H and COSY NMR and IR spectroscopy. The antibacterial effect against clinically relevant strains of S. aureus and E. coli was found to increase with increase in the degree of substitution and decrease in the spacer length of the derivatives in both the series. An optimum activity could be obtained at a degree of substitution above 0.5 for most derivatives. The trimethylammonium derivatives showed slightly higher activity than the corresponding guanidinium derivatives but a similar structure–activity relationship was obtained.

A highly efficient method for chemical modification of chitosan biopolymers by reductive amination to yield N,N-dialkyl chitosan derivatives was developed. The use of 3,6-O-di-tert-butyldimethylsilylchitosan as a precursor enabled the first 100% disubstitution of the amino groups with long alkyl chains. The corresponding mono N-alkyl derivatives were also synthesized, and all the alkyl compounds were then quaternized using an optimized procedure. These well-defined derivatives were studied for antibacterial activity against Gram positive S. aureus, E. faecalis, and Gram negative E. coli, P. aeruginosa, which could be correlated to the length of the alkyl chain, but the order was dependent on the bacterial strain. Toxicity against human red blood cells and human epithelial Caco-2 cells was found to be proportional to the length of the alkyl chain. The most active chitosan derivatives were found to be more selective for killing bacteria than the quaternary ammonium disinfectants cetylpyridinium chloride and benzalkonium chloride, as well as the antimicrobial peptides melittin and LL-37.

Here we report that grafting of a short antimicrobial peptide, anoplin, to chitosan polymers is a strategy for abolishing the hemolytic propensity, and at the same time increasing the activity of the parent peptide. Anoplin-chitosan conjugates were synthesized by CuAAC reaction of multiple peptides through 2-azidoacetyl groups on chitosan.