Preparation ofN,O-carboxymethyl chitosan nanoparticles as an insulin carrier

Grenha A., Seijo B., Remuñán-López C.

It has already been demonstrated that spray drying is a very valuable technique for producing dry powders adequate for pulmonary delivery of drugs. We have developed chitosan/tripolyphosphate nanoparticles that promote peptide absorption across mucosal surfaces. The aim of this work was to microencapsulate protein-loaded chitosan nanoparticles using typical aerosol excipients, such as mannitol and lactose, producing microspheres as carriers of protein-loaded nanoparticles to the lung. The results showed that the obtained microspheres are mostly spherical and possess appropriate aerodynamic properties for pulmonary delivery (aerodynamic diameters between 2 and 3 microm, apparent density lower than 0.45 g/cm3). Moreover, microspheres morphology was strongly affected by the content of chitosan nanoparticles. These nanoparticles show a good protein loading capacity (65-80%), providing the release of 75-80% insulin within 15 min, and can be easily recovered from microspheres after contact with an aqueous medium with no significant changes in their size and zeta potential values. Therefore, this work demonstrated that protein-loaded nanoparticles could be successfully incorporated into microspheres with adequate characteristics to reach the deep lung, which after contact with its aqueous environment are expected to be able to release the nanoparticles, and thus, the therapeutic macromolecule.

Chen S., Wu Y., Mi F., Lin Y., Yu L., Sung H.

A novel pH-sensitive hydrogel system composed of a water-soluble chitosan derivative (N,O-carboxymethyl chitosan, NOCC) and alginate blended with genipin was developed for controlling protein drug delivery. Genipin, a naturally occurring cross-linking agent, is significantly less cytotoxic than glutaraldehyde and may provide a less extent of cross-linking to form a semiinterpenetrating polymeric network (semi-IPN) within the developed hydrogel system. The drug-loading process used in the study was simple and mild. All procedures used were performed in aqueous medium at neutral environment. In the study, preparation of the NOCC/alginate-based hydrogels was reported. Swelling characteristics of these hydrogels as a function of pH values were investigated. Additionally, release profiles of a model protein drug (bovine serum albumin, BSA) from test hydrogels were studied in simulated gastric and intestinal media. The semi-IPN formation of the genipin-cross-linked NOCC/alginate hydrogel was confirmed by means of the scanning electron microscopy-energy dispersive X-ray spectrometer (SEM-EDS) and the ninhydrin assays. The percentage of decrease of free amino groups and cross-linking density for the NOCC/alginate hydrogel cross-linked with 0.75 mM genipin were 18% and 26 mol/m(3), respectively. At pH 1.2, the swelling ratio of the genipin-cross-linked NOCC/alginate hydrogel was limited (2.5) due to formation of hydrogen bonds between NOCC and alginate. At pH 7.4, the carboxylic acid groups on the genipin-cross-linked NOCC/alginate hydrogel became progressively ionized. In this case, the hydrogel swelled more significantly (6.5) due to a large swelling force created by the electrostatic repulsion between the ionized acid groups. The amount of BSA released at pH 1.2 was relatively low (20%), while that released at pH 7.4 increased significantly (80%). The results clearly suggested that the genipin-cross-linked NOCC/alginate hydrogel could be a suitable polymeric carrier for site-specific protein drug delivery in the intestine.

Pan Y., Li Y., Zhao H., Zheng J., Xu H., Wei G., Hao J., Cui F.

There are many ongoing investigations to improve the oral bioavailability of peptide and protein formulations. Bioadhesive polysaccharide chitosan nanoparticles (CS-NPs) would seem to further enhance intestinal absorption of them. In this study, Insulin-loaded CS-NPs were prepared by ionotropic gelation of CS with tripolyphosphate anions. Its particle size distribution and zeta potential were determined by photon correction spectroscopy and laser Dopper anemometry. The ability of CS-NPs to enhance intestinal absorption of insulin and increase the relative pharmacological bioavailability of insulin was investigated by monitoring the plasma glucose level of alloxan-induced diabetic rats after oral administration of various doses of insulin-loaded CS-NPs. CS-NPs had a particle size in the range of 250-400 nm and its polydispersity index was smaller than 0.1, positively charged, stable. Insulin association was found up to 80% and its in vitro release showed a great initial burst with a pH-sensitivity property. CS-NPs enhanced the intestinal absorption of insulin to a greater extent than the aqueous solution of CS in vivo. Above all, after administration of 21 I.U./kg insulin in the CS-NPs, the hypoglycemia was prolonged over 15 h and the average pharmacological bioavailability relative to SC injection of insulin solution was up to 14.9%.

Ko J.A., Park H.J., Hwang S.J., Park J.B., Lee J.S.

Chitosan microparticles were prepared with tripolyphosphate (TPP) by ionic crosslinking. The particle sizes of TPP-chitosan microparticles were in range from 500 to 710 microm and encapsulation efficiencies of drug were more than 90%. The morphologies of TPP-chitosan microparticles were examined with scanning electron microscopy. As pH of TPP solution decreased and molecular weight (MW) of chitosan increased, microparticles had more spherical shape and smooth surface. Release behaviors of felodipine as a model drug were affected by various preparation processes. Chitosan microparticles prepared with lower pH or higher concentration of TPP solution resulted in slower felodipine release from microparticles. With decreasing MW and concentration of chitosan solution, release behavior was increased. The release of drug from TPP-chitosan microparticles decreased when cross-linking time increased. These results indicate that TPP-chitosan microparticles may become a potential delivery system to control the release of drug.

Shu X.Z., Zhu K.J.

The aim of this paper was to investigate the electrostatic interactions between multivalent phosphates (phosphate (Phos), pyrophosphate (Pyro) and tripolyphosphate (TPP)) and chitosan, as well as the influence of electrostatic interactions on the properties of chitosan films ionically cross-linked by the above mentioned phosphates. The charge number of Phos was too low to interact with chitosan, while Pyro and TPP with more negative charges showed a significant ability to ionically cross-link chitosan. Solution pH played an important role on the charge numbers carried by Pyro, TPP and chitosan, especially for Pyro/chitosan. For instance, at pH less than 2.0 the interaction between Pyro and chitosan disappeared, while for TPP/chitosan even in solutions at pH less than 0.5 it still existed. Media pH and ionic strength also had a significant influence on the properties of cross-linked chitosan film with multivalent phosphates. Usually these films swelled and drug was released quickly in acidic conditions (such as in simulated gastric fluid) while under neutral conditions (such as in simulated intestinal fluid) they remained in a shrinkage state and drug was released slowly. Compared to TPP/chitosan films, Pyro/chitosan films exhibited much better pH-sensitive swelling and controlled release properties due to their relatively weak electrostatic interaction. The same reasoning was used to explain the significant acceleration of Pyro/chitosan film swelling and model drug release observed on adding sodium chloride. These films may be promising for site-specific drug delivery in the stomach.

Ma Z., Yeoh H.H., Lim L.

Previous studies on chitosan-insulin nanoparticles have reported diverse encapsulation efficiency and insulin release profiles despite similar formulation and preparation procedures. This study examined the efficiency and mechanism of association of insulin with chitosan nanoparticles in the pH range of 2.3 to 6.3. Nanoparticles of 237 to 235 nm were prepared by ionotropic gelation of chitosan with tripolyphosphate counterions. Insulin was quantified by an RP-HPLC method. The insulin association efficiency (AE) spanned a broad range from 2 to 85%, and was highly sensitive to formulation pH. Highest AE was measured at insulin loading concentrations >/= 4.28 U/mL and pH 6.1, close to the pI of native insulin and the pK(a) of chitosan. This association, attributed to physical adsorption of insulin through hydrophobic interactions with chitosan, was labile, and the associated insulin rapidly and completely released by dilution of the nanoparticles in aqueous media of pH 2 to 7.4. AE obtained at pH 5.3 was less than half that measured at pH 6.1 at corresponding insulin concentration, but the association at pH 5.3 appeared to be based on stronger interactions, because the release of insulin was pH-dependent and recovery was less than 25% even upon disintegration of the chitosan matrix. Interaction of insulin with the chitosan nanoparticles rendered the protein more susceptible to acid and enzymatic hydrolyses, the effects being more predominant in nanoparticles prepared at pH 5.3 than at pH 6.1.

Mi F.

Macroporous chitosan beads used for the immobilization of an anti-inflammatory drug were prepared by the wet phase-inversion method. There are two stages of phase-inversion observed from the cast of chitosan droplet in tripolyphosphate (TPP) aqueous solution. The first stage of phase-inversion is dominated by liquid–liquid demixing and the morphology of the freeze-dried chitosan bead shows a bundle-like porous structure. The following stage of phase-inversion is attributed to the solid–liquid demixing and the morphology of the freeze-dried chitosan bead changes to an interconnected porous structure comprising particulates around the pores. The pore size and porosity of the bead can be varied by altering synthesis conditions, such as initial polymer concentration, and the pH value and concentration of the casting agent (TPP aqueous solution). Quaternary ammonium, and aliphatic and aromatic acyl groups were introduced into the porous chitosan beads to interact with an anti-inflammatory drug, indomethacin, through the electrostatic interaction and hydrophobic interaction. The results indicated that chemical modification of the porous chitosan beads have obvious effect on the adsorption of indomethacin.

Shu X.Z., Zhu K.J.

A novel approach was developed to improve the mechanical strength of tripolyphosphate (TPP)/chitosan beads prepared under coagulation condition at 4 degrees C in the presence of gelatin. Cross-sectional analysis indicated that the beads had a homogeneous crosslinked structure, as a result the beads were strengthened greatly (the mechanical strength increased more than ten times). Furthermore sodium alginate (a polyanion) can interact with cationic chitosan on the surface of these TPP/chitosan beads to form polyelectrolyte complex film for the improvement of the drug sustained release performances. The loading efficiency of model drugs (brilliant blue and FITC-dextran) in these beads was very high (more than 90%). Crosslinking time, TPP solution pH and other preparation factors had an effect on the drug release performance of beads. The release period of brilliant blue (a poor water soluble dye) was more than 2-months at a fairly constant rate in 0.9% NaCl, 10 mM PBS pH 7.4. However, for FITC-dextran (a water soluble polysaccharide) only 1-2 days in the same conditions. It seems that TPP/chitosan bead prepared by the novel method is a promising formulation for drug delivery.

Fernández‐Urrusuno R., Calvo P., Remuñán‐López C., Vila‐Jato J.L., José Alonso M.

Purpose. To investigate the potential of chitosan nanoparticles as a system for improving the systemic absorption of insulin following nasal instillation. Methods. Insulin-loaded chitosan nanoparticles were prepared by ionotropic gelation of chitosan with tripolyphosphate anions. They were characterized for their size and zeta potential by photon correlation spectroscopy and laser Doppler anemometry, respectively. Insulin loading and release was determined by the microBCA protein assay. The ability of chitosan nanoparticles to enhance the nasal absorption of insulin was investigated in a conscious rabbit model by monitoring the plasma glucose levels. Results. Chitosan nanoparticles had a size in the range of 300−400 nm, a positive surface charge and their insulin loading can be modulated reaching values up to 55% [insulin/nanoparticles (w/w): 55/100]. Insulin association was found to be highly mediated by an ionic interaction mechanism and its release in vitro occurred rapidly in sink conditions. Chitosan nanoparticles enhanced the nasal absorption of insulin to a greater extent than an aqueous solution of chitosan. The amount and molecular weight of chitosan did not have a significant effect on insulin response. Conclusions. Chitosan nanoparticles are efficient vehicles for the transport of insulin through the nasal mucosa.

Sugimoto M., Morimoto M., Sashiwa H., Saimoto H., Shigemasa Y.

Chitosan was modified with poly(ethylene glycol)-aldehyde (PEG-aldehyde) of various molecular weights under the various molar ratios of PEG-aldehyde to chitosan. Then the prepared chitosan-PEG hybrid was converted to chitin-PEG hybrid by the acetylation with acetic anhydride. The solubility of various derivatives was investigated in three buffers of various pH. Some of these derivatives were soluble in 0.01 M phosphate buffer saline (PBS, pH = 7.2). The solubility in PBS was dependent on the degree of PEG substitution, the degree of acetylation, the molecular weight of PEG, and the weight ratio of PEG in chitin/chitosan-PEG hybrid.

Calvo P., Remu��n-L�pez C., Vila-Jato J.L., Alonso M.J.

Hydrophilic nanoparticulate carriers have important potential applications for the administration of therapeutic molecules. The recently developed hydrophobic-hydrophilic carriers require the use of organic solvents for their preparation and have a limited protein-loading capacity. To address these limitations a new approach for the preparation of nanoparticles made solely of hydrophilic polymers is presented. The preparation technique, based on an ionic gelation process, is extremely mild and involves the mixture of two aqueous phases at room temperature. One phase contains the polysaccharide chitosan (CS) and a diblock copolymer of ethylene oxide and propylene oxide (PEO-PPO) and, the other, contains the polyanion sodium tripolyphosphate (TPP). Size (200–1000 nm) and zeta potential (between +20 mV and +60 mV) of nanoparticles can be conveniently modulated by varying the ratio CS/PEO-PPO. Furthermore, using bovine serum albumin (BSA) as a model protein it was shown that these new nanoparticles have a great protein loading capacity (entrapment efficiency up to 80% of the protein) and provide a continuous release of the entrapped protein for up to 1 week. © 1997 John Wiley & Sons, Inc.

Torgal S., Subramani G., Manian R.

Interest in the biomedical field has surged due to the exploration of alternative biomaterials, particularly hydrogels and chitosan-based hydrogels. These materials present distinctive attributes such as compatibility with living systems, natural breakdown in biological environments, and economic efficiency, rendering them highly promising diverse applications. Chitosan, whether in its pure form or in combination with other polymers, has emerged as a key focus due to its potential in biomedical applications. Its immunomodulatory properties are particularly noteworthy, as they contribute to regulating immune responses, which is beneficial for tissue engineering and drug delivery purposes. Chitosan’s biodegradability ensures environmentally friendly degradation post-application, addressing concerns about long-term impact. Additionally, its interaction with the microbiome holds promise for promoting symbiotic relationships with microbial communities, crucial for maintaining homeostasis in biological environments. This comprehensive review delves into the diverse characterization methods and crosslinking techniques utilized in crafting chitosan hydrogels, modification of chitosan while also exploring their medical applications and implications in immunomodulation, biodegradability, and microbiome interaction.

Alsharbaty M.H., Naji G.A., Ali S.S.

The polysaccharides pectin and chitosan are derived from the fruit peels and exoskeletons of crustaceans and insects, respectively. Their biocompatibility and renewability make them suitable for use in food products. The size of the swelling and degradation of these cells can be controlled using different combinations. Pectin and chitosan are useful as medication delivery systems, where they can be integrated to control the dosages and residence times of pharmaceuticals. They have a wide range of applications such as wound dressings, body fat reducers, tissue engineering agents, and drug delivery agents. Addressing teeth loss with the use of dental implants is a critical element of dental care. In most cases, healing is time-consuming and painful. As a result of adding new materials to the implant surface, the healing process would accelerate, and medications would be delivered to the implant site with greater efficiency.

Dong Jing, Chen Xinyu, Li Yan, Luan Mingming, Yang Xiaodeng, Chen Hua, Koosha Mojtaba, Zhai Yuan, Fakhrullin Rawil

Chitosan, a natural and abundant polysaccharide, offers several advantageous properties, such as excellent biocompatibility, biodegradability, and antimicrobial activity, making it a highly versatile material. However, its extensive application is hindered by its insolubility in water and most organic solvents, due to numerous intramolecular/intermolecular hydrogen bonds. To overcome this limitation and optimize its benefits, chitosan is often chemically modified to enhance its utility in various industries. Biomedical materials, environmental management, biological papermaking, food preservation, and the daily chemical industry are a few examples. Modified chitosan retains the inherent properties of chitosan and acquires new physicochemical characteristics as a result of introduced functional groups. Hydrophilic modifications typically include carboxylation, phosphorylation, and quaternary ammonium modification reactions. The specific properties and applications of chitosan derivatives depend on the grafted groups. This review summarizes the reaction conditions, properties, and applications of hydrophilic chitosan derivatives in drug delivery and food preservation, serving as a reference for the development and use of chitosan-based biomaterials.The bibliography includes 128 references.

Alsharbaty M.H., Naji G.A., Ali S.S.

The polysaccharides pectin and chitosan are derived from the fruit peels and exoskeletons of crustaceans and insects, respectively. Their biocompatibility and renewability make them suitable for use in food products. The size of the swelling and degradation of these cells can be controlled using different combinations. Pectin and chitosan are useful as medication delivery systems, where they can be integrated to control the dosages and residence times of pharmaceuticals. They have a wide range of applications such as wound dressings, body fat reducers, tissue engineering agents, and drug delivery agents. Addressing teeth loss with the use of dental implants is a critical element of dental care. In most cases, healing is time-consuming and painful. As a result of adding new materials to the implant surface, the healing process would accelerate, and medications would be delivered to the implant site with greater efficiency.

Khierallah A.H., Bates I.I., Chabot B., Lajeunesse A.

Pandian M., Selvaprithviraj V., Pradeep A., Rangasamy J.

Hydrogels are excellent wound healing materials. However, due to the wear and tear at the wound site, hydrogels can lose their structural and functional integrity. To overcome this and to effectively seal the wound and control infection, an in-situ silver nanoparticles (AgNps) incorporated N , O -carboxymethyl chitosan ( N , O -CMC) based self-healing hydrogel using ethylenediaminetetraacetic acid-ferric ion (EDTA: Fe 3+ ) complex was developed. The prepared N , O -CMC/AgNps hydrogel was characterized using FTIR, SEM, and TEM. The developed N , O -CMC/AgNps hydrogel was found to be adhesive, injectable, conductive, bio-compatible, and showed antibacterial activity against ATCC and clinical strains of E. coli , K. pneumonia , P. aeruginosa , S. aureus and MRSA. N , O -CMC/AgNps hydrogel also showed anti-biofilm activity against S. aureus , E. coli , and P. aeruginosa (ATCC strains). This developed antibacterial and self-healing N , O -CMC/AgNps hydrogel can be used in the treatment of infected wounds.

Kalaithong W., Molloy R., Nalampang K., Somsunan R.

This research focused on the synthesis, characterization and property testing of the hydrogel wound dressing. It was carried out in two main parts, the first part is the synthesis and characterization of carboxymethyl chitosan (CMCTS) and the second part is preparation of hydrogels composed of the sodium 2-acrylamido-2-methylpropane sulfonate (Na-AMPS) and different compositions of CMCTS with various concentrations of poly(ethylene glycol) diacrylate (PEGDA, Mn 575) (crosslinker). CMCTS was synthesized by the direct alkylation method. After purification, the CMCTS was obtained as an off-white powder and was characterized its structure by Fourier transform infrared spectroscopy (FTIR) and proton- and carbon-13 nuclear magnetic resonance spectroscopy (1H-NMR and 13C-NMR). It was found that N,O-carboxymethyl chitosan (N,O-CMCTS) was obtained. The thermal properties of CMCTS was characterized by differential scanning calorimetry (DSC). The degree of substitution (DS) of carboxymethyl groups per chitosan repeat unit and the viscosity-average molecular weight (Mv) of the CMCTS were determined by conductivity titration and dilute-solution viscometry as 1.37 and 3.16 × 104 g/mol, respectively. Hydrogel sheets were then synthesized from Na-AMPS and CMCTS in different compositions and various concentrations of poly(ethylene glycol) diacrylate (PEGDA, Mn 575) (crosslinker). The hydrogel sheets were fabricated by UV-photopolymerization method. The CMCTS was used to blend with Na-AMPS to form semi-interpenetrating polymer network (semi-IPN). A series of hydrogel sheets were characterized in terms of their structures by FTIR, morphologies by scanning electron microscopy (SEM). Additionally, the hydrogels were determined gel content, swelling, water retention, water vapor transmission rate and mechanical properties by tensile testing. The hydrogels sheet was also investigated the skin adhesion and cytotoxicity testing with a view to their potential biomedical use as wound dressings.

Ravoor J., Amirthalingam S., Mohan T., Rangasamy J.

Antibiotic loaded calcium sulfate (CS) beads are widely reported to be used as bone void fillers. Application of these beads has been found effective in the inhibition of bacterial infections and enhanced bone regeneration, though lacking the ability to enhance angiogenesis. Thus, realizing the importance of angiogenesis for complete bone regeneration, magnesium oxide nanoparticles (MgO Nps) of ≤50 nm and tigecycline (Tg) incorporated CS based nanocomposite (Tg-NC) (Tigecycline-Nanocomposite) beads were prepared. N, O-carboxymethyl chitosan solution was chosen as a binder in the preparation of CS-based beads for the enhanced stability. The prepared Tg-NC beads were characterized using SEM, EDS and FTIR. The Tg-NC beads were cytocompatible showing pro-angiogenic property. The sustained drug release for 10 days from Tg-NC beads was found to be very effective in the inhibition of Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA). Also, Tg-NC beads effectively inhibited biofilms exhibited by Staphylococcus aureus. Thus prepared Tg-NC beads can be used as bone void fillers for inhibiting infections and promoting angiogenesis.

Shieh Y., Chen Y.

In this study, we grafted carboxymethyl chitosan (CMC) onto carbon nanotubes (CNTs), demonstrating that the CMC-grafted CNTs (CNT-g-CMCs) can disperse or aggregate in water in response to the bubbling of CO2. The CO2-switchable dispersion and aggregation of CNT-g-CMCs depend on the relative amounts of COOH to NH2 in CMC. With similar amounts of COOH and NH2 in CMC, the CNT-g-CMCs are well dispersed in water at pH 10 and exhibit no phase changes in response to the bubbling of CO2. With a higher amount of COOH than NH2 in CMC, the CNT-g-CMC dispersion in water at pH 10 becomes sensitively aggregated in response to 1 min of CO2 bubbling, but reverts to good dispersion with bubbling of N2 after 10 min. This newly developed CNT-g-CMC system with a novel CO2-responsive amphiphilic feature provides an environmentally friendly way of dispersing or aggregating CNTs in an aqueous solution without using acids and bases.

Shieh Y., Chen Y., Don T.

Carboxymethyl chitosans (CMC) with various degrees of carboxymethyl substitution were prepared and investigated on their changes in water solubility in response to bubbling of CO2 or N2 as a function of the relative concentrations of COOH and NH2 side groups. When having similar concentrations of COOH and NH2, the produced CMC was water soluble at pH 10 and consecutively experienced peculiar dissolution-to-precipitation-to-dissolution during bubbling of CO2, and experienced reverse dissolution-to-precipitation-to-dissolution process during subsequently bubbling of N2. With the concentration of COOH much higher than that of NH2, the water soluble CMC at pH 10 exhibited no phase changes in response to bubbling of CO2 and N2. This newly developed CMC solution system with novel CO2 responsive amphiphilic feature has a potential use as a CO2 switchable surfactant to control interface of mixtures of hydrophilic and hydrophobic species in emulsification/demulsification applications.

Baradaran Eftekhari R., Maghsoudnia N., Samimi S., Abedin Dorkoosh F.

Oral drug delivery is counted as the preferable route of drug administration due to its convenience, safety, and cost-effectiveness. However, many drugs are not good candidates for oral application mainly because of drug degradation within the gastrointestinal system. Overcoming the obstacles for effective oral delivery of drugs is currently one of the chief goals driving drug delivery research. Recently, remarkable advances in drug delivery technology have led to the increase in the use of various carriers for oral drug delivery. Polymers, as one of the most widely utilized tools, have demonstrated a considerable number of benefits of which stable physicochemical properties and cost-effectiveness are the prominent ones. Along with the mentioned features, an ideal polymeric delivery vehicle should be biocompatible and protect the incorporated drug from enzymatic degradation in the gastrointestinal tract. Chitosan has been extensively studied by many researchers, and a massive data is now available upon its distinctive benefits and restrictions as well as its unique characteristics appreciable for oral drug delivery. It is safe, biocompatible, low cost, and readily available. In addition, intrinsic mucoadhesion ability of chitosan urges its use as an oral drug delivery vehicle. The goal of this chapter is to focus on the application of chitosan as an oral delivery carrier for therapeutic molecules and drugs. Current conventional formulations of chitosan are first reviewed, and the related limitations are investigated to lead readers to the next sections in which novel approaches for improved delivery system are explained as fully as possible. Application of chitosan in oral gene and peptide delivery is explained as separate sections since these two areas have been attracting much attention in recent years due to the intrinsic properties of chitosan making it a promising candidate in the areas. Different strategies employed to improve chitosan polymers regarding physicochemical and targeting properties are covered throughout the script. Diverse modification approaches as well as their limitations are explained, exemplified, and illustrated within the body of the chapter. In the end, the future concept of chitosan oral drug delivery is argued followed by a concise summary.

Villegas-Peralta Y., Correa-Murrieta M.A., Meza-Escalante E.R., Flores-Aquino E., Álvarez-Sánchez J., Sánchez-Duarte R.G.

Nanoparticles of chitosan–tripolyphosphate through two ionic gelation methods (Np1 and Np2) with different dosages of TPP and stirring time were prepared and characterized (FTIR, TEM, SEM–EDS, AFM, XRD, DLS and BET) for the removal of an allura red dye. Np1 and Np2 were obtained with a diameter size of 315.5 nm and 437.4 nm, respectively, both with low polydispersity. The influence on smaller particle size was defined by a low concentration of chitosan solution (0.2 mg/mL) and a higher dosage of TPP (1 mg/mL), while the stirring time did not affect the particle size. Dye removal was placed in batch mode by varying adsorbent dosage, time and pH. The removal percentage (R%) in Np1 decreased with an increase in adsorbent dosage at pH 4 and 6, while Np2 remained constant at pH 2, 4 and 6. Adsorption essays in Np1 and Np2 revealed that under pH 2, an adsorbent dosage of 0.01 g and a contact time of 5 min, the adsorptions are complete. Np2 was recognized as the best adsorbent in comparison with Np1 due to the highest R% under several pHs. This research has demonstrated that the obtained nanoparticles by ionic gelation are suitable for removal of azo dyes in water.

Wu S., Liu X., Miller A.L., Cheng Y., Yeh M., Lu L.

In the present study, we fabricated non-toxic, injectable, and thermo-sensitive NIPAAm-g-chitosan (NC) hydrogels with thiol modification for introduction of disulfide cross-linking strategy. Previously, NIPAAm and chitosan copolymer has been proven to have excellent biocompatibility, biodegradability and rapid phase transition after injection, suitable to serve as cell carriers or implanted scaffolds. However, weak mechanical properties significantly limit their potential for biomedical fields. In order to overcome this issue, we incorporated thiol side chains into chitosan by covalently conjugating N-acetyl-cysteine (NAC) with carbodiimide chemistry to strengthen mechanical properties. After oxidation of thiols into disulfide bonds, modified NC hydrogels did improve the compressive modulus over 9 folds (11.4 kPa). Oscillatory frequency sweep showed a positive correlation between storage modulus and cross-liking density as well. Additionally, there was no cytotoxicity observed to mesenchymal stem cells, fibroblasts and osteoblasts. We suggested that the thiol-modified thermo-sensitive polysaccharide hydrogels are promising to be a cell-laden biomaterial for tissue regeneration.

Bai X., Kong M., Xia G., Bi S., Zhou Z., Feng C., Cheng X., Chen X.

pH-responsive nanoparticles (NPs) comprised of degradable carboxymethyl chitosan (CMCS) crosslinked with CaCl2 were simply prepared via ionic gelation. Fabrication conditions including insulin dosage, CMCS concentration, and crosslinking density were systematically investigated for insulin loading and release in vitro. The encapsulation efficiencies (EE), loading capacity (LC) and average size of the NPs decreased with the increasing insulin concentrations (

Fonseca-Santos B., Chorilli M.

Chitin is one of the most abundant natural polymers in the world and is used for the production of chitosan by deacetylation. Chitosan is nontoxic and biodegradable and, therefore, can be used as a biomaterial and for the construction of drug delivery systems. Nevertheless, the poor solubility of chitosan in neutral or alkalinized media has restricted its applications in the pharmaceutical and biomedical fields. Chitosan can be easily carboxymethylated to improve its solubility in aqueous media while its biodegradability and biocompatibility are preserved. Carboxymethyl chitosans show improved solubility in aqueous media, which makes them an attractive alternative source for producing biomaterials and drug delivery systems as well as for designing nanotechnology-based systems. Thus, carboxymethyl chitosan-based materials have a wide applicability and good potential in the development of biomedical nanodevices and controlled release drug formulations. This review summarizes preparations and properties of hydrophilic chitosan-based materials such as nanoparticles, microparticles, tablets, and films as well as procedures related to various practical applications.