Carboxymethyl-hexanoyl Chitosan Research Articles

Chitosonic® Acid as a Novel Cosmetic Ingredient: Evaluation of its Antimicrobial, Antioxidant and Hydration Activities.

Chitosonic® Acid, carboxymethyl hexanoyl chitosan, is a novel chitosan material that has recently been accepted by the Personal Care Products Council as a new cosmetic ingredient with the INCI (International Nomenclature of Cosmetic Ingredients) name Carboxymethyl Caprooyl Chitosan. In this study, we analyze several important cosmetic characteristics of Chitosonic® Acid. Our results demonstrate that Chitosonic® Acid is a water-soluble chitosan derivative with a high HLB value. Chitosonic® Acid can form a nano-network structure when its concentration is higher than 0.5% and can self-assemble into a nanosphere structure when its concentration is lower than 0.2%. Chitosonic® Acid has potent antimicrobial activities against gram-positive bacteria, gram-negative bacteria and fungus. Chitosonic® Acid also has moderate DPPH radical scavenging activity. Additionally, Chitosonic® Acid exhibits good hydration activity for absorbing and retaining water molecules with its hydrophilic groups. From a safety point of view, Chitosonic® Acid has no cytotoxicity to L-929 cells if its concentration is less than 0.5%. Moreover, Chitosonic® Acid has good compatibilities with various normal cosmetic ingredients. Therefore, we propose that Chitosonic® Acid has the potential to be a widely used ingredient in various types of cosmetic products.

Improved pH-responsive amphiphilic carboxymethyl-hexanoyl chitosan–poly(acrylic acid) macromolecules for biomedical applications

In this communication, we report a new type of amphiphilic carboxymethyl-hexanoyl chitosan (CHC)–poly(acrylic acid) (PAA) hybrid macromolecule, which was successfully prepared through polymerization of acrylic acid (AA) in the presence of amphiphilic CHC. The chemical structure of the hybrid was characterized by FT-IR and 1H NMR, which confirmed a chemical linkage between the amine groups of CHC and hydroxyl groups of AA. This CHC–PAA hybrid exhibited amphiphilic property as the original CHC rendering the self-assembling capability to be tunable in terms of AA concentration. Compared with the existing pristine chitosan–PAA co-polymers, this CHC–PAA hybrid exhibited a relatively high pH-responsive volumetric change by 10–100 times compared with the existing alternatives reported in the literature. The hybrid nanoparticles showed excellent encapsulation efficiency greater than 90% for a hydrophobic anti-cancer substance, (S)-(+)-camptothecin. A pH-responsive drug release behavior was systematically evaluated. Besides, this hybrid also revealed excellent cytocompatibility towards the MCF-7 and BCE cell lines, which, associated with its structural stability, suggests this new type of CHC–PAA hybrid to be a promising biomaterial for oral drug delivery application.

Evaluation of Carboxymethyl-Hexanoyl Chitosan as a Protein Nanocarrier

Carboxymethyl-hexanoyl chitosan (CHC) has the ability to self-assemble into nanocapsules in an aqueous solution and it has recently shown potential in numerous biomedical applications. Here we investigate the protein loading efficiency and release, as well as the structural properties of CHC protein nanocarriers. Bovine serum albumin (BSA) or its chromophore labelled version, fluorescein-BSA, was used as a model protein and the loading was performed with a simple mixing of pre-formed nanocapsules and protein. Dynamic light scattering and zeta potential analysis revealed that protein loaded nanocarriers with high positive zeta potential were formed. The protein loaded nanocarriers displayed a loading efficiency of 75% and a very slow protein release. In summary, our results highlight the potential of CHC as a protein nanocarrier, but also indicate that protein-CHC interactions need to be considered in protein containing CHC formulations where protein release is not the main function.

A novel ultrasound-triggered drug vehicle with multimodal imaging functionality

A novel remotely triggered drug vehicle having multimodal imaging functionality was developed. It exhibits magnetic resonance (MR) imaging, ultrasound (US) imaging, encapsulation of a hydrophobic agent and US-triggered release behavior. Lipophilic superparamagnetic iron oxide (SPIO) nanoparticles were self-assembled with an amphiphilic chitosan derivative, carboxymethyl hexanoyl chitosan (CHC), to form superparamagnetic CHC/SPIO micelles and then loaded with camptothecin (a hydrophobic anticancer agent). The superparamagnetic micelles were then conjugated with albumin-based microbubbles (MBs) to form superparamagnetic micelle-decorated MBs (CHC/SPIO-decorated MBs). The albumin MBs and CHC/SPIO-decorated MBs both demonstrated in vitro concentration-dependent US imaging contrast. Interestingly, the in vitro US contrast was enhanced by decoration. In vivo US images showed that the B-mode contrast of the proposed vehicles could be clearly observed in the veins and arteries of Sprague–Dawley rats. Moreover, the proposed vehicle exhibited significant US-triggered release behavior under therapeutic US sonication at a frequency of 1MHz and power density of 2.4Wcm−2 for 30min. However, similar behavior was not observed under diagnostic US bombardment at a frequency of 12MHz and mechanical index of 0.5. On the other hand, in vitro MR images of the CHC/SPIO-micelle-decorated MBs also revealed a significant concentration-dependent T2 (spin–spin relaxation time) contrast due to their decoration with superparamagnetic micelles. Most importantly, the r2∗-r2 value of the CHC/SPIO-decorated MBs decreased after therapeutic US bombardment for 30min. This might be considered as an index to probe destruction of the drug-loaded CHC/SPIO micelles.

Corneal repair by human corneal keratocyte-reprogrammed iPSCs and amphiphatic carboxymethyl-hexanoyl chitosan hydrogel

Induced pluripotent stem cells (iPSCs) have promising potential in regenerative medicine, but whether iPSCs can promote corneal reconstruction remains undetermined. In this study, we successfully reprogrammed human corneal keratocytes into iPSCs. To prevent feeder cell contamination, these iPSCs were cultured onto a serum- and feeder-free system in which they remained stable through 30 passages and showed ESC-like pluripotent property. To investigate the availability of iPSCs as bioengineered substitutes in corneal repair, we developed a thermo-gelling injectable amphiphatic carboxymethyl-hexanoyl chitosan (CHC) nanoscale hydrogel and found that such gel increased the viability and CD44 + proportion of iPSCs, and maintained their stem-cell like gene expression, in the presence of culture media. Combined treatment of iPSC with CHC hydrogel (iPSC/CHC hydrogel) facilitated wound healing in surgical abrasion-injured corneas. In severe corneal damage induced by alkaline, iPSC/CHC hydrogel enhanced corneal reconstruction by downregulating oxidative stress and recruiting endogenous epithelial cells to restore corneal epithelial thickness. Therefore, we demonstrated that these human keratocyte-reprogrammed iPSCs, when combined with CHC hydrogel, can be used as a rapid delivery system to efficiently enhance corneal wound healing. In addition, iPSCs reprogrammed from corneal surgical residues may serve as an alternative cell source for personalized therapies for human corneal damage.

Electrospinning of Amphipathic Chitosan Nanofibers for Surgical Implants Application

Novel amphipathic derivative of chitosan (carboxymethyl-hexanoyl chitosan, CHC) was made into mats of nanofibers (approximately 100 nm) via electrospinning. The resulting mats were further cross-linked with genipin. The morphology of CHC nanofibers was examined using a field emission scanning electron microscope (FESEM). The optimum parameters of CHC nanofiber was achieved when the CHC concentration was 4 wt% and electrospinning was conducted with a voltage of 20 kV over a distance of 10 cm. The characterizations of biocompatibility, hemocompatibility, and anti-bacterial activity of the nanofibers were also investigated. The results show that CHC nanofibers still preserved antibacterial activity and thrombogeneicity owing to those residual amino groups of chitosan and exhibit high biocompatibility for L929 fibroblast test. Thus CHC exhibited the potential to serve as a novel wound dressing and surgical implants application by these advanced features.

Nano-hybrid carboxymethyl-hexanoyl chitosan modified with (3-aminopropyl)triethoxysilane for camptothecin delivery

Silane-modified amphiphilic chitosan was synthesized by anchoring a silane coupling agent, (3-aminopropyl)triethoxysilane, to a novel amphiphilic carboxymethyl-hexanoyl chitosan (CHC). The chemical structure of this new organic–inorganic hybrid molecule was characterized by FTIR and 13C-, 29Si-nuclear magnetic resonance, while the structural evolution was examined using scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), and dynamic light scattering (DLS). Experimental results indicated a self-assembly behaviour of molecules into nanoparticles with a stable polygonal geometry, consisting of ordered silane layers of 6nm in thickness. The self-assembly property was found to be influenced by chemical composition and concentration of silane incorporated, while the size can be varied by the amount of anchored silane. It was also demonstrated that such vesicle exhibited excellent cytocompatibility and cellular internalization capability in ARPE-19 cell line, and presented well-controlled encapsulation and release profiles for (S)-(+)-camptothecin. These unique properties render it as a potential drug delivery nanosystem.

Magnolol-Loaded Core–Shell Hydrogel Nanoparticles: Drug Release, Intracellular Uptake, and Controlled Cytotoxicity for the Inhibition of Migration of Vascular Smooth Muscle Cells

Encapsulation and release behavior of a water-insoluble drug, magnolol, using a core-shell polysaccharide-based nanoparticle, manipulating the cellular internalization and controlled cytotoxic effect of magnolol-loaded nanoparticles over the A10 vascular smooth muscle cells (VSMCs) was reported. A magnolol-polyvinylpyrrolidone (PVP) core phase was prepared, followed encapsulating by an amphiphilic carboxymethyl-hexanoyl chitosan (CHC) shell to form a magnolol-loaded core-shell hydrogel nanoparticles (termed magnolol-CHC nanoparticles). The resulting magnolol-CHC nanoparticles were employed for evaluation of drug release and controlled cytotoxic inhibition of VSMCs migration in vitro. A sustained release of the magnolol from the nanoparticles was determined. The magnolol-CHC nanoparticles exhibited outstanding cellular uptake efficiency, and under a cytotoxic evaluation, an increased antiproliferative effect and effective inhibition of VSMC migration as a result of efficient intracellular delivery of the encapsulated magnolol in comparison to free magnolol was achieved. We then envision a potential intracellular medication strategy with improved biological and therapeutic efficacy using the magnolol-CHC nanoparticles illustrated in this work.

Novel pH-sensitive chitosan-based hydrogel for encapsulating poorly water-soluble drugs

Carboxymethyl–hexanoyl chitosan (CHC) is an amphiphilic chitosan derivative with excellent swelling ability and water solubility under natural conditions. In this work, the influence of the degree of carboxymethyl and hexanoyl substitution on the pH-sensitive swelling behavior, drug release behavior, and antiadhesion behavior of CHC hydrogels (cross-linked with genipin) were studied. It was found that the pH sensitivity was more pronounced in CHC than in N,O-carboxymethyl chitosan because the hexanoyl group altered the state of water in CHC by inhibiting intermolecular hydrogen bonding. In addition, greater pH sensitivity was observed in samples bearing longer hydrophobic chains (carboxymethyl–palmityl chitosan). Interestingly, when used with ibuprofen (a poorly water-soluble therapeutic agent used here as a model drug), the bursting release of the drug was less prominent in the CHC samples having a high degree of carboxymethyl substitution. The CHC hydrogel also demonstrated good cell compatibility and its antiadhesive ability after grafting was altered by changes in the degree of hexanoyl substitution.

Self-Assembled Hollow Nanocapsule from Amphiphatic Carboxymethyl-hexanoyl Chitosan as Drug Carrier

A new type of amphiphilic chitosan, which was synthesized through the use of both hydrophilic carboxymethyl and hydrophobic hexanoyl substitutions, was employed to self-assemble into a hollow nanocapsule in an aqueous environment. Critical aggregation concentration (cac) and zeta potential were experimentally identified for the amphiphilic chitosan (CHC). Both experimental data suggested that the self-assembly behavior of the CHC is fundamentally determined as an interplay between the hydrophobic interaction and the variation of the zeta potential upon hexanoyl substitution, which further influenced the nanostructural evolution of the nanocapsules. Higher hexanoyl substitution promoted larger nanocapsules, ca. 200 nm in diameter, while a reduced zeta potential was correspondingly detected, and vice versa, forming smaller nanocapsules, ca. 20 nm in diameter. The self-assemble mechanism, together with the corresponding nanostructural stability, of this unique CHC nanocapsule was also proposed in terms of in...

Synthesis and Characterization of Amphiphatic Carboxymethyl-hexanoyl Chitosan Hydrogel: Water-Retention Ability and Drug Encapsulation

Carboxymethyl-hexanoyl chitosan (NOCHC) amphiphatic hydrogel with excellent water-absorption and water-retention abilities under neutral conditions was successfully synthesized for the first time and then employed as a carrier for delivering amphiphatic agents. NOCHC is a water-soluble chitosan derivative bearing the carboxymethyl (hydrophilic) group and the hexanoyl (hydrophobic) group, which was synthesized using N,O-carboxymethyl chitosan (NOCC) as the starting precursor. Water-absorption ability (W(c)), water-retention ability, and drug encapsulation efficiency of the NOCHC hydrogel were investigated in terms of the degree of carboxymethyl and hexanoyl substitution. It was found that the amount of moisture uptake was dependent on the relative humidity as well as degree and nature of such substitution. The hexanoyl substitution affected significantly the water-absorption ability by altering the number of water-binding sites and the state of water under low humidity and the fully swollen state, respectively. In addition, the presence of hydrophobic hexanoyl substitution significantly retards water mobility during deswelling, causing better water-retention ability. Moreover, compared with that of pristine chitosan and NOCC, the encapsulation efficiency of ibuprofen (partially hydrophobic agent) was significantly enhanced with the incorporation of the hexanoyl group. These results demonstrate that the newly developed NOCHC amphiphatic hydrogel showed enhanced water-absorption ability, water-retention ability, and amphiphatic drug encapsulation efficiency compared with NOCC and chitosan.

Effect of Hydroxyapatite Nanoparticles on Ibuprofen Release from Carboxymethyl-Hexanoyl Chitosan/O-Hexanoyl Chitosan Hydrogel

In order to explore the effect of nanofiller on the regulation of the drug release behavior from microsphere-embedded hydrogel prepared by carboxymethyl-hexanoyl chitosan (HNOCC) and O-hexanoyl chitosan (OHC), the release kinetics was investigated in terms of various amounts of calcium-deficient hydroxyapatite (CDHA) nanoparticles incorporated. HNOCC is a novel chitosan-based hydrophilic matrix with a burst release profile in a highly swollen state. The drug release kinetics of the HNOCC hydrogel can be regulated by incorporation of well-dispersed CDHA nanoparticles. It was found that the release duration of ibuprofen (IBU) from HNOCC was prolonged with increasing amounts of CDHA which acts as a crosslink agent and diffusion barrier. On the contrary, the release duration of the IBU from OHC (hydrophobic phase) was shortened through increasing the CDHA amount over 5%, which is due to the hydrophilic nature of the CDHA nanoparticles destroying the intermolecular hydrophobic interaction and accelerating OHC degradation. Thus, water accessibility and molecular relaxation were enhanced, resulting in a higher release rate. In addition, sustained and sequential release behavior was achieved by embedding the OHC microspheres (hydrophobic phase) into the HNOCC (hydrophilic phase) matrix, which could significantly prolong the release duration of the HNOCC drug-loaded implant.