Carboxymethyl Chitosan Nanoparticles Research Articles

ROS-responsive carboxymethyl chitosan nanoparticles loaded with astaxanthin for alleviating oxidative damage in intestinal cells

The controlled release of antioxidant substances at the intestinal oxidative damage site is crucial for alleviating intestine-related diseases. Herein, the novel ROS-responsive carrier was synthesized through simple amidation reaction between carboxymethyl chitosan (CMC) and methionine (Met), a natural organic compound containing ROS-responsive linkages (thioether). Initially, astaxanthin (AXT) nanoparticles (AXT2@CMT) with excellent stability and drug loading capacity (39.68 ± 0.23 μg/mL) were prepared by optimizing various reaction conditions. In the simulated high-concentration ROS environment of the intestine, CMT achieved a transition from hydrophobic groups (thioether) into hydrophilic groups (sulfone), which was conducive to the controlled release of AXT. In vitro cell experiments revealed that AXT2@CMT could effectively alleviate the oxidative damage in intestinal epithelioid cell line No. 6 (IEC-6 cell) caused by H2O2. This study achieved a straightforward preparation of ROS-responsive nanocarrier through food ingredients, offering a theoretical foundation for the controlled release of AXT at the intestinal oxidative damage site.

Preparation of pH-sensitive carboxymethyl chitosan nanoparticles loaded with ginsenoside Rb1 and evaluation of drug release in vitro

Oral absorption of ginsenoside Rb1 (Rb1) is often hindered by the gastrointestinal tract. Carboxymethyl chitosan deoxycholic acid loaded with ginsenoside Rb1 nanoparticles (CMDA@Rb1-NPs), were prepared as a delivery system using a self-assembly technique with amphipathic deoxycholic acid grafted carboxymethyl chitosan as the carrier, which improved the stability and embedding rate of Rb1. In addition, the CMDA@Rb1-NPs was encapsulated with sodium alginate by ion crosslinking method with additional layer (CMDAlg@Rb1-NPs). Scanning electron microscopy showed that the nanoparticles were spherical, evenly distributed, smooth and without obvious adhesion. By evaluating drug loading, entrapment efficiency, the encapsulation efficiency of Rb1 increased from 60.07 % to 72.14 % after grafting deoxycholic acid improvement and optimization. In vitro release results showed that the cumulative release of Rb1 by CMDAlg-NPs showed a pH dependent effect, which was <10 % in simulated gastric juice with pH 1.2, completely released with pH 7.4 for about 48 h. In addition, Rb1 and CMDAlg@Rb1-NPs had inhibitory effects on A549 cells, and the inhibitory effect of CMDAlg@Rb1-NPs was better. Therefore, all results indicated that CMDA/Alg@Rb1 nanoparticles might be a novel drug delivery system to improve the stability and embedding rate of Rb1, and has the potential to be applied in oral pharmaceutical preparations.

Assessment of the cytotoxic effect of carboxymethyl chitosan-loaded amygdalin nanoparticles against human normal and cancer cell lines

In recent years, the development of antitumor drugs has been dedicated to natural products. Amygdalin is a natural herbal cyanoglycoside that has anticarcinogenic effect on many types of cancers once hydrogen cyanide (HCN) is released. The main objective of the present study is to synthesize and investigate the potential of carboxymethyl chitosan nanoparticles (CMC NPs) as drug delivery agents for amygdalin encapsulation and its delivery to cancer and normal cell lines. In this study, carboxymethyl chitosan nanoparticles encapsulated with amygdalin (CMC-Am NPs) were prepared and characterized through their particle size, surface charge, chemical structure and dielectric properties. Also, the invitro drug release of amygdalin from CMC NPs was studied. Additionally, the cytotoxcity of the amygdalin and CMC-loaded amygdalin NPs were evaluated through MTT assay. The results showed that the prepared CMC-loaded amygdalin NPs exhibited a small particle size of 129 nm, high zeta potential value of − 43 mV and confirmed the amygdalin stability and compatibility with CMC NPs. Furthermore, the CMC NPs demonstrated sustained release of amygdalin during 24 h. Moreover, compared to free amygdalin, amygdalin-loaded CMC NPs have significant anti-cancerous effect on human colon HCT-116 and breast MCF-7 cancer cell lines while being safe on normal cells BJ1. In conclusion, CMC NPs can be employed as an efficient drug delivery vehicle for controlled and sustained amygdalin release with enhanced cytotoxicity on malignant cells without harming normal cells.

Effects of miR-214 on adenosine A2A receptor and carboxymethyl chitosan nanoparticles on the function of keloid fibroblasts and their mechanisms

This work prepared and investigated the impact of carboxymethyl chitosan nanoparticles (MC-NPs) on the proliferative capability of keloid fibroblasts (KFBs) while analyzing the mechanistic roles of miR-214 and adenosine A2A receptor (A2AR) in fibroblasts within hypertrophic scars. MC-NPs were synthesized through ion cross-linking, were characterized using transmission electron microscopy (TEM) and laser particle size scattering. The influence of MC-NPs on the proliferation capacity of KFBs was assessed using the MTT method. Changes in the expression levels of miR-214 and A2AR in KFBs, normal skin fibroblasts (NFBs), hypertrophic scar tissue, and normal skin tissue were analyzed. KFBs were categorized into anti-miR-214, anti-miR-NC, miR-214 mimics, miR-NC, si-A2AR, si-con, anti-miR-214+ si-con, and anti-miR-214+ si-A2AR groups. Bioinformatics target prediction was conducted to explore the interaction between miR-214 and A2AR. Real-time quantitative PCR and immunoblotting (WB) were employed to detect the expression levels of miR-214, A2AR, apoptotic protein Bax, and TGF-β in different cells. Cell counting kit-8 (CCK8) and flow cytometry were employed to assess cell proliferation activity and apoptosis. The results indicated that MC-NPs exhibited spherical particles with an average diameter of 236.47 ± 4.98 nm. The cell OD value in the MC-NPs group was lower than that in KFBs (P < 0.05). The mRNA levels of miR-214 in KFBs and hypertrophic scar tissue were lower than those in NFBs and normal tissue (P < 0.001), while the mRNA and protein levels of A2AR were significantly elevated (P < 0.05). Compared to the control group and anti-miR-NC, the anti-miR-214 group showed significantly increased cell OD values and Bcl-2 protein expression (P < 0.001), decreased levels of apoptotic gene Bax protein, TGF-β gene mRNA, and protein expression (P < 0.001). Continuous complementary binding sites were identified between miR-214 and A2AR. Compared to the control group, the si-A2AR group exhibited a significant decrease in A2AR gene mRNA and protein expression levels (P < 0.001), reduced cell viability (P < 0.001), increased apoptosis rate (P < 0.001), and a significant elevation in TGF-β protein expression (P < 0.001). miR-214 targetedly regulated the expression of A2AR, inducing changes in TGF-β content, promoting the proliferation of keloid fibroblasts, and inhibiting cell apoptosis.

Curcumin-loaded pH-sensitive carboxymethyl chitosan nanoparticles for the treatment of liver cancer

In this study, the pH-responsive API-CMCS-SA (ACS) polymeric nanoparticles (NPs) based on 1-(3-amino-propyl) imidazole (API), stearic acid (SA), and carboxymethyl chitosan (CMCS) were fabricated for the effective transport of curcumin (CUR) in liver cancer. CUR-ACS-NPs with various degrees of substitution (DS) were employed to prepare through ultrasonic dispersion method. The effect of different DS on NPs formation was discussed. The obtained CUR-ACS-NPs (DSSA=12.4%) had high encapsulation rate (more than 85%) and uniform particle size (186.2 ± 1.42 nm). The CUR-ACS-NPs showed better stability than the other groups. Drug release from the CUR-ACS-NPs was pH-dependent, and more than 90% or 65% of CUR was released in 48 h in weakly acid medium (pH 5.0 or 6.0, respectively). Additionally, the CUR-ACS-NPs increased the intracellular accumulation of CUR and demonstrated high anticancer effect on HepG2 cells compared with the other groups. CUR-ACS-NPs prolonged the retention time of the drug, and the area under the curve (AUC) increased significantly in vivo. The in vivo antitumor study further revealed that the CUR-ACS-NPs exhibited the capability of inhibiting tumor growth and lower systemic toxicity. Meanwhile, CUR, CUR-CS-NPs, and CUR-ACS-NPs could be detected in the evaluated organs, including tumor, liver, spleen, lung, heart, and kidney in distribution studies. Among them, CUR-ACS-NPs reached the maximum concentration at the tumor site, indicating the tumor-targeting properties. In short, the results suggested that CUR-ACS-NPs could act a prospective drug transport system for effective delivery of CUR in cancer treatment.

A bioactive composite hydrogel dressing that promotes healing of both acute and chronic diabetic skin wounds

Mesenchymal stem cell derived exosomes (MSC-Exos) demonstrate beneficial effects on wound healing via anti-inflammatory and angiogenic properties. Chitosan (CS) exhibits excellent biocompatibility and accelerates cellular migration, adhesion, and proliferation. The ions released from bioactive glass (BG) and titanium dioxide (TiO2) nanoparticles exhibit sustained angiogenic and antibacterial potency. In this study, CMCS-CEBT hydrogel was synthesized from exosomes encapsulated carboxymethyl chitosan (CMCS), chitosan nanoparticles (CS-NPs), BG, and TiO2 nanoparticles for a preliminary evaluation of its impacts on the treatment of full-thickness skin defects, diabetic wounds, and burn skin injury due to burns. In vitro analysis indicated that the hydrogel exhibits excellent cell compatibility, stimulates endothelial cell adhesion and proliferation, and presents anti-inflammatory, angiogenic, and antibacterial activities. In vivo, the composite hydrogel dressing accelerated a wound healing acceleration effect, stimulated angiogenesis, and increased collagen deposition and the expression of anti-inflammatory factors. This innovative composite hydrogel dressing as a potential clinical therapy, utilizing bioactive materials, holds promise as a potential clinical therapy that aims to facilitate the regeneration of acute and chronically damaged skin tissue.

Chitosan and its amphiphilic derivative nanoparticles loaded with Minoxidil for induction of hair growth: In vitro and in vivo evaluation

Minoxidil is widely used for treating Androgenic Alopecia, but its low hydrophilicity promotes the use of co-solvents in commercial formulations, which could then cause skin irritations. Nano-drug delivery systems have been developed to improve the solubility of lipophilic molecules and increase the concentration of drugs in hair follicles, thereby minimizing side effects. Chitosan (CS) and Methylated Aminobenzyl Carboxymethyl Chitosan (MCS) nanoparticles containing Minoxidil were prepared and evaluated for their physicochemical properties, drug release profile, skin permeation, cytotoxicity, and animal hair growth. The results showed that MCS nanoparticles had a 60 % drug release compared to CS nanoparticles, with almost complete release in 2 h. MCS nanoparticles also showed a 20 % drug permeation from skin compared to 70 % for CS nanoparticles in 24 h. In 48 and 72 h, CS and MCS nanoparticles didn't exhibit any significant cytotoxicity. Animal study revealed a significant increase in hair growth from MCS nanoparticles compared to the commercial formulation in fourteen days. However, MCS nanoparticles were less efficient compared to CS nanoparticles. The use of MCS in nano-drug delivery systems is expected to continue to gain importance due to its ability to enhance the solubility of hydrophobic drugs, particularly in the treatment of skin diseases.

Strategies to prolong drug retention in solid tumors by aggregating Endo-CMC nanoparticles

Developing a highly effective nano-drug delivery system with sufficient drug permeability and retention in tumors is still a major challenge for oncotherapy. Herein, a tumor microenvironment responsive, aggregable nanocarriers embedded hydrogel (Endo-CMC@hydrogel) was developed to inhibit the tumoral angiogenesis and hypoxia for enhanced radiotherapy. The antiangiogenic drug (recombinant human endostatin, Endo) loaded carboxymethyl chitosan nanoparticles (Endo-CMC NPs) was wrapped by 3D hydrogel to comprise the Endo-CMC@hydrogel. After peritumoral injection, the Endo-CMC NPs were released, invaded deeply into the solid tumor, and cross-linked with intratumoral calcium ions. The cross-linking process enabled these Endo-CMC NPs to form larger particles, leading to long retention in tumor tissue to minimize premature clearance. This Endo-CMC@hydrogel, integrating the abilities of good tumoral penetration, long retention of anti-drug, and alleviation of hypoxia in tumor tissue, greatly improved the therapeutic effect of radiotherapy. This work provides a proof-of-concept of tumor microenvironment-responding and an aggregable nano-drug delivery system as promising antitumor drug carriers for effective tumor therapy.

A new soft tissue constructed with chitosan for wound dressings-incorporating nanoparticles for medical and nursing therapeutic efficacy

The skin, being the largest organ in the human body, plays a vital role in shielding internal organs from external physical and chemical factors. However, skin damage caused by various factors such as injuries, surgeries, diabetes, or burns can lead to wounds that diminish the skin's protective function. Monitoring essential physiological parameters like temperature, moisture, and pH is crucial to facilitate antibiotic treatment, remote physician monitoring, patient comfort, cost reduction, and prevention of hospital-acquired infections. To this end, innovative wound coverings made of biological materials like gelatin, carboxymethyl chitosan, and titanium nanoparticles have been developed, mainly for hospital and pediatric applications. These wound coverings come equipped with sensors to monitor temperature, pH, and moisture and are suitable for pediatric hospitals where children experience difficulty in wound healing due to their sensitive skin. The temperature monitoring feature allows physicians to accurately assess the wound's temperature, detect potential infections, and take prompt actions. These wound coverings can significantly enhance wound treatment for patients, as real-time monitoring of physiological parameters enables informed decision-making by physicians, leading to better therapeutic outcomes. Furthermore, the use of these wound coverings can minimize the risk of hospital-acquired infections. Their adaptability and flexibility make them ideal for various wound types and sizes, ensuring patient comfort and compliance with the treatment plan. In conclusion, the development of innovative and flexible wound coverings using biological materials and equipped with sensors represents a significant breakthrough in wound management. The use of these wound coverings has the potential to revolutionize wound care and improve patient outcomes, particularly in pediatric hospitals where wound healing is often challenging.

Carboxymethyl chitosan nanoparticles loaded with Ctenopharyngodon idella interferon-γ2 (CiIFN-γ2) enhance protective efficacy against bacterial infection in grass carp

Type II interferon may be one of the most important immunomodulatory factors involved in the coordination of immune responses in vertebrates, but the efficacy of protein molecular drugs in treating bacterial infection still needs to be improved. Therefore, stable delivery technologies are required to improve the efficacy of proteins. This work evaluates the feasibility and biological activity of the carboxymethyl chitosan (CMCS) load with the interferon-γ2 of Ctenopharyngodon idella (CiIFN-γ2). Moreover, the resistance to Aeromonas hydrophila infection in grass carp will also be examined. The nanoparticle based on CMCS load with CiIFN-γ2 was constructed and designated as CMCS-CiIFN-γ2 (CMCS-Ciγ2) by ion exchange method. The CMCS-loading protein efficiency was measured at 28.46 ± 2.87%. The hemolytic analysis and cytotoxicity assays were performed to assess the biocompatibility of CMCS-Ciγ2. The cytotoxicity of CMCS-Ciγ2 nanoparticles was 90.8 ± 0.95% at the highest tested concentration (200 μg/mL), which proves that it is safe and non-toxic. Additionally, the findings indicated that the expression levels of pro-inflammatory cytokines (IL-1β, TNF-α, iNOS) in macrophages activated by nanoparticles CMCS-Ciγ2, were significantly enhanced, and nitric oxide (NO) was detected at high levels. In vivo imaging system (IVIS) results showed that the CMCS-Ciγ2 can still be detected at 8 h after oral gavage. This remains inside the host for a longer period of time contributing to the effective uptake of the protein. The challenge test revealed that CMCS-Ciγ2 had a higher relative immune protection rate than other treatment groups. The findings also showed that there was a reduction in tissue bacterial loads and damage. The in-vivo experiment results showed that the CMCS-Ciγ2 elicited higher levels of serum biochemical indexes and increased expressions of several immune-related genes (IL-1β, TNF-α) in grass carp. In turn, these results demonstrated that the CMCS-Ciγ2 can effectively regulate the immune system and facilitate the development of an immune barrier that enables the host to cope with external environment changes. This research will provide critical insights into the development and application of nanomaterials, which can be used to prevent and treat bacterial diseases in aquaculture.

Synthesis of carboxmethyl chitosan and its effect on budesonide colon sensitive nano release system

In this investigation, colon sensitive nanoparticles were prepared using different agents by ion-gelation method. The carboxymethyl chitosan nanoparticles (CMCH-NPs) were used to deliver budesonide to the colon. The formation of Carboxymethyl chitosan (CMCH) was confirmed by H1NMR, FTIR, and degree of substitution (Ds). CMCH-NPs were evaluated for drug excipient interaction, loading efficiency % (LE), entrapment efficiency % (EE), scanning electron microscopy (SEM), zeta potential, particle size distribution, in-vitro release studies (also with enzymes), cytotoxicity, and stability studies. In-vitro release studies by dialysis bag method without enzymes revealed that N4 and N6 showed less than 10% cumulative drug release (% CDR) in pH1.2. SEM results of N6 showed spherical shaped aggregates and smoother surfaces than N4. Consequently, the presence of pepsin in pH 1.2, diastase in pH 4.5 and pancreatin in pH 7.4 buffers did not have any significant effect on the release kinetics of the N6 CMCH-NPs. On addition of the colonic enzymes in 10th hour, there was a marked increase in the release of budesonide (upto 98.27% ± 1.30%) due to the action of enzymes produced by the colonic microflora which causes the lysis of glycosidic bonds. The evidence for pH sensitivity along with the microbiotic activation of the CMCH-NPs in the colon was thus established. The cell viability (%) in all samples was above 96%, ensuring the biocompatibility of CMCH in the dose range of 0.2–2.4 mg/mL. Stability studies as per ICH Q1A (R2) guidelines were found to be stable.

Design and characterization of an antibacterial film composited by hydroxyethyl cellulose (HEC), carboxymethyl chitosan (CMCS), and nano ZnO for food packaging

For food packaging, a novel composite film was prepared by solution casting method using hydroxyethyl cellulose (HEC), carboxymethyl chitosan (CMCS), and zinc oxide nanoparticles as raw materials. The composite film successfully compounded the nanoparticles, as deduced by spectroscopy, crystallography and morphology observation. The addition of CMCS and ZnO enhanced the solvent resistance (the water solubility of the composite film was reduced by 94.3 %) and UV shielding ability (the UV shielding capacity of the composite film was increased by 45.73 %) of the composite film, thus improving the application prospects of the composite film in water-rich foods. In addition, the synergistic effect of CMCS and ZnO helped the composite film to efficiently inhibit the pathogenic bacteria Listeria monocytogenes and Pseudomonas aeruginosa (rate of inhibition>99.99 %) in food. The addition of CMCS and ZnO also significantly improved the elasticity (improve 494.34 %) and maximum load capacity (improve 142.24 %) of the composite film.

Injectable carboxymethyl chitosan/nanosphere-based hydrogel with dynamic crosslinking network for efficient lubrication and sustained drug release

The typical symptoms of arthritis are inflammation and lubrication deficiency in joints, which increase wear of articular cartilage along with pain of patients. In the present study, one kind of novel macromolecular/microsphere-based injectable hydrogels (CMC-ODex NPs) with dual functionalities of drug release and lubrication, was fabricated via dynamic Schiff base crosslinking network between carboxymethyl chitosan (CMC) and oxidation dextran nanoparticles (ODex NPs). The CMC-ODex NPs hydrogels exhibited typical viscosity-thinning phenomenon at wide range of shear rates and obvious gel-sol transition feature at specific strain. As a result, CMC-ODex NPs hydrogels presented low friction coefficient at the sliding interface of bovine articular cartilages, resulting from the boundary lubrication of hydrogel and the rolling friction effect of ODex NPs. Furthermore, the anti-inflammatory drug (dexamethasone, DXM) encapsulated in ODex NPs exhibited sustainable drug release behavior during the dynamic shearing process, which making CMC-ODex NPs hydrogels possessed good and stable anti-inflammatory effect. CMC-ODex NPs hydrogels was prepared without utilizing any toxic agents, thus demonstrated excellent cytocompatibility. Our experimental results reveal the CMC-ODex NPs hydrogels is promising to be used as functional lubricant for inhibiting the development of arthritis.

The effect of insulin-loaded gold and carboxymethyl chitosan nanoparticles on gene expression of glucokinase and pyruvate kinase in rats with diabetes type 1.

The goal of this study was to see how effective subcutaneous (SC) insulin is and two different types of oral insulin-loaded nanoparticles (INS) including carboxymethyl chitosan nanoparticles (CMCNPs) and gold nanoparticles (AuNPs) separately and compare their effects on glucokinase, pyruvate kinase gene expressions, and other parameters in diabetes type one male Wistar rats. Seven groups of ten male Wistar rats for each group were formed at random including four control groups (n= 10) and three treatment groups (n= 10). The control groups consisted of four control groups (10 rats for each) and three treatment groups (10 rats for each). Normal control rats were not given any treatment, as were diabetic rats that were not given any treatment, and diabetic rats that were given oral nanoparticles (CMCNPs and AuNPs). Diabetic rats were given subcutaneous insulin, oral insulin-loaded carboxymethyl chitosan nanoparticles (INS-CMCNPs), and oral insulin-loaded gold nanoparticles (INS-AuNPs). The rats were treated for the final 3 weeks of the experiment, which lasted 4 weeks. CMCNPs and AuNPs presented a promising effect on pyruvate kinase and Glucokinase gene expressions compared to subcutaneous insulin. We also discovered that conjugating insulin to CMCNPs and AuNPs protects them from the insulin-degrading enzyme, which offers managed bioavailability. Furthermore, we investigated the effects of CMCNPs and AuNPs on several parameters and discovered that both have a significant effect in vivo, which enables glucose level regulation, and improves patient organ activity for better glucose consumption. PRACTICAL APPLICATIONS: In this paper, we discussed the effect of oral INS-CMCNPs and INS-AuNPs, and compared their effects on Glucokinase and pyruvate kinase gene expressions and other biochemical parameters in diabetes type one male Wistar rats. On the other hand, we investigated the impact of oral INS and subcutaneous insulin separately on the same parameters and their effect on the histology of the liver and pancreas of diabetic rats. According to our research, as we discussed the different mechanisms of INS-CMCNPs and INS-AuNPs, they presented a promising effect compared to SC insulin. They can be used to keep oral insulin safe from the environment of the gastrointestinal system to overcome all the barriers, improve the therapeutic, and clinical outcomes of insulin by maintaining its desired concentration inside the body, ending the panic of the patient from receiving insulin by the SC injection by increasing his satisfaction with receiving accurate oral insulin doses.

Anthocyanin Encapsulated Nanoparticles as a Pulmonary Delivery System.

Anthocyanins are known for their therapeutic efficacy for many human diseases, including cancer. After ingestion, anthocyanins degrade due to oxidation and enzymatic breakdown, resulting in reduced therapeutic efficacy. Direct delivery to target tissues and entrapment of anthocyanins increases their stability, bioavailability, and therapeutic efficacy. The objective of the present study was to develop a direct delivery system of anthocyanins into pulmonary tissues via encapsulated nanocarriers. A cyanidin-3-O-glucoside (C3G)-rich anthocyanin extract was prepared from well-ripened haskap (Lonicera caerulea L.) berries (HB) and encapsulated in three different polymeric nanocarrier systems: polyethylene glycol-poly(lactide-co-glycolide), maltodextrin, and carboxymethyl chitosan (CMC). The anthocyanin encapsulation efficiency was significantly higher in CMC (10%) than in the other two polymers. The cytotoxicity and cytoprotective effect of HB anthocyanin-encapsulated CMC (HB-CMC, 4 μg of C3G equivalent anthocyanin in 2 mg/mL nanoparticle) and anthocyanin-free CMC (E-CMC, 2 mg/mL) were tested for cytotoxicity using human normal lung epithelial BEAS-2B cells. The CMC nanoparticles were not cytotoxic for BEAS-2B cells. The HB-CMC nanoparticles reduced carcinogen-induced oxidative stress in BEAS-2B cells and restored the expression of superoxide dismutase and glutathione peroxidase enzymes. The HB-CMC nanoparticles also reduced carcinogen-induced DNA single-strand breaks and alkaline-labile sites but not the double-strand breaks. The E-CMC, HB-CMC (28 μg C3G equivalent/mouse/day for six days), or the same dose of free HB anthocyanin was administered to A/JCr mice through a nose-only passive inhalation device. C3G and its metabolites, cyanidin, peonidin-3-O-glucoside, and cyanidin-3-O-glucuronide, were detected by UPLC/ESI/Q-TOF-MS in the lungs of mice after one hour of exposure. Therefore, the CMC could be a promising noncytotoxic candidate to encapsulate HB anthocyanin. Direct delivery of anthocyanin to lung tissues enhances tissue retention, slows phase 2 metabolism, and improves therapeutic efficacy.

Mussel-inspired polysaccharide-based sponges for hemostasis and bacteria infected wound healing

Effective bleeding control and wound protecting from infection play critical roles in the tissue healing process. However, local hemostats are not involved in the whole healing processes to promote the final healing efficiency. Here, a multi-functional mussel-inspired polysaccharide-based sponge with hemostatic, antibacterial and adhesive properties was fabricated via cryopolymerization of oxidized dextran (OD), carboxymethyl chitosan (CC) and polydopamine nanoparticles (PDA-NPs), followed by lyophilization. Combining with the adsorbed thrombin, the sponges yielded a considerably lower amount of blood than the commercially available hemostatic dressings. Benefiting from the high photo-thermal transition efficiency of PDA-NPs, the sponges exhibited excellent antibacterial activity to both gram positive and negative bacteria. Owing to the rapid hemostatic activity and effective infection resistance, the sponges illustrated the significantly acceleratory wound healing efficiency compared with the control group. The thrombin-loaded OD/CC-PDA polysaccharide-based sponge has great potential for future clinical use as wound dressing.

Diselenide-crosslinked carboxymethyl chitosan nanoparticles for doxorubicin delivery: Preparation and in vivo evaluation

In this paper, we report a simple approach to fabricate diselenide-crosslinked carboxymethyl chitosan nanoparticles (DSe-CMC NPs) for doxorubicin (DOX) delivery, with disulfide analogs (DS-CMC NPs) as control. DS-CMC NPs and DSe-CMC NPs featured a spherical morphology and narrow size distribution with the average size about 200 nm. Carboxymethyl chitosan (CMC) as the starting material not only improved the biocompatibility of the nanocarriers but also enhanced physiological stability. Due to electrostatic interactions between DOX and CMC, the nanoparticles had high drug encapsulation efficiency (∼25 %). The nanoparticles disintegration and drug release were accelerated by the cleavage of diselenide bonds through oxidation by H2O2 or reduction by GSH. In vitro cell experiments revealed that DOX-loaded DSe-CMC NPs possessed the highest drug accumulation and cytotoxicity in tumor cells. Moreover, DOX-loaded DSe-CMC NPs performed the enhanced growth inhibition in vivo than that of DS-CMC NPs. Thus, the diselenide-crosslinked nanoparticles possess great potentials for DOX delivery.

Development of Carboxymethyl Chitosan Nanoparticles Prepared by Ultrasound-Assisted Technique for a Clindamycin HCl Carrier.

Polymeric nanoparticles are one method to modify the drug release of small hydrophilic molecules. In this study, clindamycin HCl was used as a model drug loaded in carboxymethyl chitosan nanoparticles cross-linked with Ca2+ ions (CMCS-Ca2+). The ultrasonication with experimental design was used to produce CMCS-Ca2+ nanoparticles loading clindamycin HCl. The model showed that the size of nanoparticles decreased when amplitude and time increased. The nanoparticle size of 318.40 ± 7.56 nm, decreased significantly from 543.63 ± 55.07 nm (p < 0.05), was obtained from 75% of amplitude and 180 s of time, which was one of the optimal conditions. The clindamycin loading content in this condition was 34.68 ± 2.54%. The drug content in nanoparticles showed an inverse relationship with the size of the nanoparticles. The sodium carboxymethylcellulose film loading clindamycin HCl nanoparticles exhibited extended release with 69.88 ± 2.03% drug release at 60 min and a gradual increase to 94.99 ± 4.70% at 24 h, and demonstrated good antibacterial activity against S. aureus and C. acne with 40.72 ± 1.23 and 48.70 ± 1.99 mm of the zone of inhibition at 24 h, respectively. Thus, CMCS-Ca2+ nanoparticles produced by the ultrasound-assisted technique could be a potential delivery system to modify the drug release of small hydrophilic antibiotics.

Oleogel-based Pickering emulsions stabilized by ovotransferrin–carboxymethyl chitosan nanoparticles for delivery of curcumin

This work prepared food-grade oleogel-based Pickering emulsion stabilized by ovotransferrin (OVT)–carboxymethyl chitosan (CMCS) nanoparticles (OPEOC). The analysis of emulsified phase volumes and stability index exhibited that OPEOC with different volumes of oil fraction remained stable for 2 months of storage. The prepared Pickering emulsions were used as delivery systems for curcumin. In vitro digestive studies showed that OPEOC significantly improved the degree of lipolysis and the bioaccessibility of curcumin compared to the sunflower seed oil-based oleogel. The oleogel-based Pickering emulsions fabricated in the present study had noticeable storage stability, high loading and improved bioaccessibility of nutraceuticals, which might provide new insights into the development of novel food-grade Pickering emulsions with excellent properties.

Effect of 5-luorouracil Carboxymethyl Chitosan Nanoparticles on the Apoptosis Level of Keloid Fibroblasts

Objective to investigate the effect of 5-fluorouracil (5-FU) loaded carboxymethyl chitosan (CMC) nanoparticles on the apoptosis level of keloid fibroblasts. Methods keloid tissue (n = 80) was taken from inpatient and outpatient patients who were treated in our hospital from January 2020 to December 2020. The fresh keloid specimen tissues were washed with saline three times. After removing the epithelium, they were cut into 2mmx2mm tissue blocks for subculture. CMC nanoparticles loaded with 5-FU were prepared by ionically crosslinking CMC solution with calcium chloride. The viability of fibroblasts was determined by MTT assay. Transwell was used to assess fibroblast invasion. The wound healing test was used to evaluate the migration of fibroblasts. The apoptotic cells were analyzed by Annexin V-FITC and flow cytometry. The expression of apoptotic protein in fibroblasts was determined by Western blot analysis. The expression of transforming growth factor-β (TGF-β) and Smad2/3 were analyzed by immunohistochemistry. The mRNA expression of ERK1/2, protein kinase B (AKT) and nuclear transcription factor-κB (NF-κB) was analyzed by RT-qPCR. Results compared with the control group, there was no difference in the viability of fibroblasts in the nanoparticle group at 0h (P&gt;0.05), and the viability of fibroblasts at 24h, 48h and 72h decreased by 37.29%, 29.58% and 28.38, respectively (P&lt;0.05). Compared with the control group, the fiber cells composed of nanoparticles were less likely to pass through the pores of the basement membrane and their invasiveness decreased (P&lt;0.05). Compared with the control group, the migration ability of fibroblasts in the nanoparticle group decreased (P&lt;0.05). Compared with the control group, the apoptotic rate of fibers composed of nanoparticles increased (P&lt;0.05). Compared with the control group, the expression levels of Bax, Caspase-3 and Caspase-9 apoptotic proteins in the nanoparticle group increased (P&lt;0.05). Compared with the control group, the expression levels of TGF-β and Smad2/3 in the nanoparticle group decreased (P&lt;0.05). Compared with the control group, the expression levels of ERK1/2, Akt and NF-κB mRNA in the nanoparticle group decreased (P&lt;0.05). Conclusion 5-FU loaded CMC nanoparticles could reduce fibrosis in keloids, lower cell proliferation, migration and invasion, and increase cell apoptosis by inhibiting TGF-β related pathways.