Charged Carboxymethyl Chitosan Research Articles

Biopolymer hydrogel matrices for the stabilization and in-vitro delivery of anti-cancer polyoxometalate [CoW11O39(CpTi)]7−

In the present study, the polyoxometalate (POM), [CoW11O39(CpTi)]7−, known for its significant anti-cancer activity and relatively low toxicity compared to established organic drugs such as CP and 5FU, is investigated. However, it is acknowledged that POMs inherently exhibit toxicity to living cells due to the presence of heavy and toxic metal ions within their core structures and their limited selectivity toward biological targets. Consequently, a methodology to mitigate this toxicity is sought by encapsulating these POMs within hydrogel matrices, with the intention to facilitate slow, sustained release and enhanced target specificity. In this study, the hydrogel of the well-researched anti-cancer POM, K6H[CoW11O39(CpTi)] (hereafter abbreviated as CoW11CpTi), is synthesized through the electrostatic interaction of the positively charged carboxymethyl chitosan (CMC), carboxymethyl cellulose (CMCell), and gelatin, which serve as hydrogelators. Subsequent characterization of the resultant CMC-CoW11CpTi, CMCell-CoW11CpTi, and gelatin-CoW11CpTi gels is performed utilizing Fourier Transform Infrared Spectroscopy (FT-IR), Differential Scanning Calorimetry/Thermogravimetric Analysis (DSC/TGA), Electron Spin Resonance (ESR) Spectroscopy, Scanning Electron Microscopy (SEM), and Tgel analysis. Among these, the gelatin-CoW11CpTi gel demonstrates the highest stability, retaining its structural integrity for in excess of 10 days. In addition, cytotoxicity assays are conducted on an assortment of cell lines including NRK52e (Rattus norvegicus kidney cell line), MDA-MB-231 (human breast adenocarcinoma), and MCF-7 (human breast epithelial adenocarcinoma). It is observed that the release of POM from the hydrogel matrices under physiological pH conditions exhibits a slow and sustained profile. This study therefore offers a promising approach for the effective delivery of POMs in cancer therapy.

Identification of inflammatory regulation roles of thalidomide/ruxolitinib in nucleus pulposus and construction of polyelectrolyte nanocomplexes-impregnated injectable hydrogels for synergistic intervertebral disk degeneration treatment

Degeneration of the intervertebral discs (IVD) is an important underlying etiology of degenerative diseases contributor to lower back and neck pain. Alleviation of inflammation is recognized as the most direct way for the treatment of IVD. Repurposing of approved drugs is a viable alternative strategy to de novo drug discovery and development. The aim of this study is to identify the inflammatory regulation roles of the small molecule thalidomide (an immunomodulatory and TNF-α inhibitor) and ruxolitinib (a selective JAK1/2 inhibitor) in nucleus pulposus (NP) cells and investigate the combinational therapeutic potentials of thalidomide and ruxolitinib for ameliorating IVD degeneration. RNA-sequencing (RNA-seq) was used to detect differentially expressed genes (DEGs) after treatment of human NP cells with individual thalidomide and ruxolitinib, and relevant signaling pathways and functions of DEGs were detected by enrichment analysis. Western blot and immunofluorescence were applied to explore the mechanisms by which thalidomide and ruxolitinib regulated inflammatory factors in human NP cells. Moreover, we developed ruxolitinib and thalidomide co-delivered polyelectrolyte nanocomplexes (RTNPs) by the assembly of chitosan derivatives of positively charged chitosan hydrochloride (CS) and negatively charged carboxymethyl chitosan (CMCS). In vitro studies revealed that RTNPs could efficiently deliver drugs into NP cells and corresponding extracellular matrix (ECM)-related genes and proteins were adjusted. Furthermore, The RTNPs were assembled with Pluronic F127 to form a RTNPs/F127 injectable thermoresponsive hydrogels to maintain resident time within the nucleus pulposus, achieve sustained drugs release and achieve long-term therapy effects. The caudal disc degeneration model of SD rats was established by acupuncture, and X-ray, magnetic resonance scanning, μCT scanning, and histological methods were performed to detect the therapeutic effects of RTNPs/F127 hydrogel on IVD in vivo. As was demonstrated in the in vivo studies, in situ intradiscal injection of RTNPs/F127 composite displayed a relatively slower disc degenerating progression in a puncture-induced IVD rat model compared with the monotherapy pattern.

New synthetic adriamycin-incorporated chitosan nanoparticles with enhanced antioxidant, antitumor activities and pH-sensitive drug release

In this paper, adriamycin-incorporated chitosan nanoparticles were synthesized by ionic gelation using negatively charged carboxymethyl chitosan and positively charged 2-hydroxypropyltrimethyl ammonium chloride chitosan. The method was efficient to obtain nanoparticles with low polydispersity index and small hydrodynamic diameter. And high zeta potential value indicated that nanoparticles had good stability. The adriamycin release of nanoparticles represented a significant response to pH, with the fastest release in phosphate buffer solution at pH 6.8. Meanwhile, the antioxidant efficiency of nanoparticles was assayed, and nanoparticles represented significant enhancement in radicals scavenging activity. The assay of cell viability by CCK-8 test exhibited that nanoparticles led to statistically significant decrease in cell viability for four kinds of cancer cells (HEPG-2, A549, MCF-7, and BGC-823). It was indicated that the nanoparticles with enhanced biological activity, reduced cytotoxicity, and pH-sensitive release could be served as potential drug carrier in drug delivery system.

The immunostimulatory effects of hydroxypropyltrimethyl ammonium chloride chitosan-carboxymethyl chitosan nanoparticles

In this study, we generated chitosan nanoparticles by exploiting the electrostatic interactions between positively charged hydroxypropyltrimethyl ammonium chloride chitosan (HACC) and negatively charged carboxymethyl chitosan (CMC), and examined the effects of altering the molecular weight and carboxymethyl substitution sites of the chitosan molecules. Particle size, potential, and encapsulation efficiency of the various chitosan nanoparticles were examined; the particle size range was 162.40–332.80 nm, the charge range was 19.50–40.60 mV, and the encapsulation efficiency range was 48.4–70.7%. We then examined the immunostimulatory effects of the nanoparticle variants on dendritic cells (DCs); we found that the site of carboxymethyl substitution significantly affected the immunostimulatory effects of the nanoparticles. Two nanoparticle types, 200 kDa N,O-carboxymethyl chitosan-HACC (NO-CMC-HACC) and N-carboxymethyl chitosan-HACC (N-CMC-HACC), greatly promoted the expression of interleukin-6, tumor necrosis factor, and interleukin-1β in DCs. Moreover, NO-CMC-HACC nanoparticles caused an increase in major histocompatibility complex-II (MHC-II), CD11c, CD80, and CD86 secretion in DCs, indicating that these nanoparticles promoted antigen presentation. We then examined chitosan nanoparticle uptake by DCs using laser confocal microscopy; we found that the NO-CMC-HACC nanoparticles were more readily absorbed by DCs compared to the N-CMC-HACC nanoparticles. Therefore, we concluded that 200 kDa NO-CMC-HACC nanoparticles exhibited strong potential as immunological adjuvants.

Functionalizing a Polyelectrolyte Complex with Chitosan Derivatives to Tailor Membrane Surface Properties

Polyelectrolyte complex (PEC) materials show promise in the development of tunable membranes for aqueous and organic solvent separations, as well as in the creation of surface layers for fouling control. In this study, we developed a polyelectrolyte complex (PEC) functionalized by negatively charged carboxymethyl chitosan (CMC-) and positively charged quaternized chitosan (QC+) to tailor its surface properties and antibacterial efficacy. CMC- and QC+ were prepared and characterized using FT-IR and 1H NMR, which confirmed the presence of the carboxymethyl group and trimethylammonium group in CMC- and QC+ with 65.6% and 83.9% substitution, respectively. The CMC- functionalized PEC (CMC-/PEC) and QC+ functionalized PEC materials (QC+/PEC) were evaluated for their stability in water, resistance to organic and inorganic adsorption, and antibacterial action against a model microorganism, Pseudomonas putida. The results showed no release of chitosan derivatives after adsorption, and CMC-/PEC and QC+/PEC exhibited charge-based, selective repulsion of model organic and inorganic substances. Moreover, the functionalized PEC surfaces displayed lower bacterial attachment due to their smoother surfaces as compared to the bare ceramic membrane and their antimicrobial properties. Among the PEC samples, CMC-/PEC had the lowest cell attachment, while QC+/PEC showed the highest attachment due to electrostatic attraction. The ceramic and bare PEC surfaces were negligibly bactericidal, while cell viability decreased to 34.4 ± 10.2% and 30.6 ± 8.2% with the CMC-/PEC and QC+/PEC surfaces, respectively. In the filtration experiments, the unmodified PEC and CMC-/PEC showed lower rates of flux decline due to organic fouling than did the bare ceramic or QC+/PEC due to electrostatic repulsion. Furthermore, PECs as protective layers promoted much higher flux recoveries than simply backwashing the uncoated membranes. This surface tunability, then, enhances the potential of PECs either as fouling resistant materials or as a method to create a sacrificial, protective layer on surfaces that once fouled can be dissolved and re-established.

Improvement of the separation and antibiological fouling performance using layer-by-layer self-assembled nanofiltration membranes

A novel surface-modified nanofiltration (NF) membrane was prepared by layer-by-layer (LbL) self-assembly of positively charged polyethylenimine (PEI) and glutaraldehyde (GA) and negatively charged carboxymethyl chitosan (NO-CMC) alternately on the polyethersulfone (PES) membrane surfaces. The alteration aimed at improving the membrane separation performance, which was investigated in the study. In order to enhance antibiological fouling performance of the NF membrane, the silver nanoparticles (AgNPs) were coated on the modified membrane in two different modes. Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM), atomic force microscopy (AFM), zeta potential measurement, and water contact angle measurements were employed to characterize the formed membrane surface chemical composition and morphology. The rejection of different single nonheavy metal salts, yielded from the modified membrane, followed the order of MgCl2 > MgSO4 > CaCl2 > Na2CO3 > NaCl > Na2SO4. Additionally, the rejection of single heavy metal salts Cr3+, Cu2+, Cd2+, Ni2+ was 88.95%, 84.04%, 82.69% and 83.47%, respectively, whereas the rejection of Cr3+, Cu2+, Cd2+, Ni2+ increased to 91.77%, 90.70%, 89.74% and 87.22%, respectively, in the mixed salt solution. Moreover, the rejection of Cu2+ and Cd2+ increased to 96.12% and 94.38% after adjusting pH. As a result of loading the AgNPs on the modified membrane with a suitable mode, the antibiological fouling ability of the membrane was immensely improved by AgNPs.

PH-Triggered Charge-Reversal Mesoporous Silica Nanoparticles Stabilized by Chitosan Oligosaccharide/Carboxymethyl Chitosan Hybrids for Effective Intracellular Delivery of Doxorubicin.

Surface modification of mesoporous silica nanoparticles (MSNs) is a promising way to enhance therapeutic efficacy and minimize side effects of anticancer drugs. In this work, MSNs with reduced particle size and optimum pore diameter were obtained and catalyzed by ammonia/triethanolamine. In view of the negatively charged carboxymethyl chitosan (CMC) and positively charged chitosan oligosaccharide (CS), the pH-triggered charge-reversal CS/CMC bilayer was designed as a stimuli-responsive switch for MSNs via the protonation and deprotonation effect. The results showed that MSNs-CS/CMC were core-shell and mesoporous in structure. Surface charge conversion and pH dependence were clearly observed in the doxorubicin hydrochloride (DOX) delivery. The intracellular uptake indicated that DOX@MSNs-CS/CMC could be distributed in the cytoplasm of MCF-7 cells and exhibited lower toxicity, which would improve the stability and prolong the retention time compared to free DOX and unmodified DOX@MSNs at pH 7.4. Moreover, the cellular uptake and internalization of DOX@MSNs-CS/CMC were enhanced to promote drug delivery into the cell nucleus at pH 6.5. The biocompatible and surface-charge-reversible MSNs-CS/CMC have the potential to prolong the retention time in the bloodstream, facilitate the endosome escape, and enrich the targeted antitumor strategy, providing an alternative platform for efficient drug delivery in breast cancer therapy.

Carboxymethyl chitosan/phospholipid bilayer-capped mesoporous carbon nanoparticles with pH-responsive and prolonged release properties for oral delivery of the antitumor drug, Docetaxel

In this article, a new type of carboxymethyl chitosan/phospholipid bilayer-capped mesoporous carbon nanomatrix (CCS/PL/MC) was fabricated as a potential nano-drug delivery system. In this drug delivery system, a mesoporous carbon nanomatrix (MC) acts as the support for loading drug molecules, a positively charged phospholipid (PL) layer works as the inner shell for prolonged drug release and a negatively charged carboxymethyl chitosan (CCS) layer serves as the outer shell for pH-responsive drug release. Docetaxel (DTX) was selected as a model drug. The drug-loaded CCS/PL/MC was synthesized via a combination approach of double emulsion/solvent evaporation followed by lyophilization. The drug-loaded nanoparticles were characterized for their particle size, structure, morphology, zeta (ζ)-potential, specific surface area, porosity, drug loading and solid state. In vitro drug release tests showed that the drug-loaded CCS/PL/MC nanoparticles possess a good pH-sensitivity and prolonged releasing ability with negligible release in gastric media and controlled release in intestinal media. Compared with MC and PL-capped MC, CCS/PL/MC had a greater mucoadhesiveness. Moreover, cellular uptake study indicated that CCS/PL/MC might improve intracellular drug delivery. These results suggest that this hybrid nanocarrier, combining the beneficial features of CCS, PL and MC, is a promising drug delivery system able to improve the oral absorption of antitumor drugs.

Antimicrobial activity and cytotoxicity of N-2-HACC and characterization of nanoparticles with N-2-HACC and CMC as a vaccine carrier

This study developed, for the first time, the N-2-hydroxypropyltimehyl ammonium chloride chitosan (N-2-HACC)/carboxymethyl chitosan (CMC) complex nanoparticles as a delivery carrier for the Newcastle disease virus (NDV). Nanoparticles were developed by complexation between the positively charged N-2-HACC and negatively charged CMC without using any crosslinkers. The structure and properties of these synthesized derivatives were characterized by Fourier transform infrared (FTIR) spectroscopy, proton nuclear magnetic resonance (1H NMR) spectroscopy, and X-ray diffraction (XRD) technologies. The antimicrobial activity of N-2-HACC against a Gram-positive bacteria (Staphylococcus aureus), four Gram-negative bacteria (Escherichia coli, Enterobacter aerogenes, Pseudomonas aeruginosa, and Enterobacter cloacae), and a fungus (Candida albicans), and its cytotoxicity were characterized in order to facilitate its use as a novel material for biomedical applications. The results indicated that the N-2-HACC had been prepared successfully and showed high antimicrobial activity against the tested bacteria and fungus, very low toxicity, and a high safety level. The water solubility and degree of substitution (DS) of the chitosan derivatives were also analyzed, and the effects of solution concentration on the mean diameter Polydispersity (PDI) and the Zeta potential of the blank nanoparticles were discussed. Tests of the N-2-HACC/CMC complex nanoparticles as a carrier for NDV revealed stable and long lasting release of the antigen. The western blotting analysis showed that NDV structural proteins were detected in the NDV-N-2-HACC/CMC-NPs. NDV was found to be released in the virus release assay of NDV-N-2-HACC/CMC-NPs. Based on these results, the N-2-HACC and CMC will be a new drug release carrier with great application potential.