Estudio de biocompatibilidad de matrices poliméricas combinadas, responsivas al pH, con aplicación en Ingeniería de Tejido Óseo / Biocompatibility study of combined pH-responsive polymeric matrices with application in Bone Tissue Engineering

El presente trabajo muestra la obtención de un material a partir de un polímero sintético (TerP) y otro natural, mediante entrecruzamiento físico y su caracterización fisicoquímica y biológica, con el fin de emplearlos para regeneración de tejido óseo. Las membranas fueron obtenidas por la técnica de evaporación del solvente y caracterizadas por espectroscopia FTIR, ensayos de hinchamiento, medidas de ángulo de contacto y microscopia electrónica de barrido (SEM). Se encontró que la compatibilidad entre los polímeros que la constituyen es estable a pH fisiológico y que, al incorporar mayor cantidad del TerP a la matriz, esta se vuelve más hidrofóbica y porosa. Además, teniendo en cuenta la aplicación prevista para dichos materiales, se realizaron estudios de biocompatibilidad y citotoxicidad con células progenitoras de médula ósea (CPMO) y células RAW264.7, respectivamente. Se evaluó la proliferación celular, la producción y liberación de óxido nítrico (NO) al medio de cultivo durante 24 y 48 horas y la expresión de citoquinas proinflamatorias IL-1ß y TNF-α de las células crecidas sobre los biomateriales variando la cantidad del polímero sintético. Se encontró mayor proliferación celular y menor producción de NO sobre las matrices que contienen menos proporción del TerP, además de poseer una mejor biocompatibilidad. Los resultados de este estudio muestran que el terpolímero obtenido y su combinación con un polímero natural es una estrategia muy interesante para obtener un biomaterial con posibles aplicaciones en medicina regenerativa y que podría extenderse a otros sistemas estructuralmente relacionados. (AU)

In the present work, the preparation of a biomaterial from a synthetic terpolymer (TerP) and a natural polymer, physically crosslinked, is shown. In order to evaluate the new material for bone tissue regeneration, physicochemical and biological characterizations were performed. The membranes were obtained by solvent casting and characterized using FTIR spectroscopy, swelling tests, contact angle measurements, and scanning electron microscopy (SEM). It was found that the compatibility between the polymers is stable at physiological pH and the incorporation of a higher amount of TerP into the matrix increases hydrophobicity and porosity.Furthermore, considering the intended application of these materials, studies of biocompatibility and cytotoxicity were conducted with Bone Marrow Progenitor Cells (BMPCs) and RAW264.7 cells, respectively. Cell proliferation, NO production and release into the culture medium for 24 and 48 hours, and proinflammatory cytokine expression of IL-1ß and TNF-α from cells grown on the biomaterials while varying the amount of the synthetic polymer were evaluated. Greater cell proliferation and lower NO production were found on matrices containing a lower proportion of TerP, in addition to better biocompatibility. The results of this study demonstrate that the obtained terpolymer and its combination with a natural polymer is a highly interesting strategy for biomaterial preparation with potential applications in regenerative medicine. This approach could be extended to other structurally related systems. (AU)

The protective effect of N-acetylcysteine against liposome and chitosan-induced cytotoxicity.

AIM: N-acetylcysteine (NAC) is an antioxidant used to moderate liposome and chitosan-induced cell cytotoxicity at their high concentrations. METHODS: Liposome and chitosan were prepared and characterised. The cytotoxicity effect of liposome with NAC-loaded liposome (liposome-NAC) and chitosan solution with chitosan solution containing NAC (chitosan-NAC) on the A549 cell line was compared. RESULTS: Particle size, zeta potential, and NAC drug release for liposome were 125.9 ± 8 nm, -34.7 ± 2.1 mV, and 51.1% ± 3%, respectively. Scanning electron microscope (SEM) and transmission electron microscope (TEM) indicated spherical shape of liposome. Encapsulation efficiency of liposome-NAC was 12% ± 0.98%. Particle size and zeta potential for chitosan solution were 361 ± 11.3 nm and 10.8 ± 1.52 mV. Stability storage study indicated good stability of chitosan and liposome. Cell viability of liposome-NAC and chitosan-NAC significantly was higher than liposome and chitosan at all four concentrations. CONCLUSIONS: NAC has a protective effect against liposome and chitosan-induced cell toxicity.

In vivo toxicity evaluation of tumor targeted glycol chitosan nanoparticles in healthy mice: repeated high-dose of glycol chitosan nanoparticles potentially induce cardiotoxicity.

BACKGROUND: Glycol chitosan nanoparticles (CNPs) have emerged as an effective drug delivery system for cancer diagnosis and treatment. Although they have great biocompatibility owing to biodegradable chemical structure and low immunogenicity, sufficient information on in vivo toxicity to understand the potential risks depending on the repeated high-dose have not been adequately studied. Herein, we report the results of in vivo toxicity evaluation for CNPs focused on the number and dose of administration in healthy mice to provide a toxicological guideline for a better clinical application of CNPs. RESULTS: The CNPs were prepared by conjugating hydrophilic glycol chitosan with hydrophobic 5ß-cholanic acid and the amphiphilic glycol chitosan-5ß-cholanic acid formed self-assembled nanoparticles with its concentration-dependent homogeneous size distributions (265.36-288.3 nm) in aqueous condition. In cell cultured system, they showed significantly high cellular uptake in breast cancer cells (4T1) and cardiomyocytes (H9C2) than in fibroblasts (L929) and macrophages (Raw264.7) in a dose- and time-dependent manners, resulting in severe necrotic cell death in H9C2 at a clinically relevant highly concentrated condition. In particular, when the high-dose (90 mg/kg) of CNPs were intravenously injected into the healthy mice, considerable amount was non-specifically accumulated in major organs (liver, lung, spleen, kidney and heart) after 6 h of injection and sustainably retained for 72 h. Finally, repeated high-dose of CNPs (90 mg/kg, three times) induced severe cardiotoxicity accompanying inflammatory responses, tissue damages, fibrotic changes and organ dysfunction. CONCLUSIONS: This study demonstrates that repeated high-dose CNPs induce severe cardiotoxicity in vivo. Through the series of toxicological assessments in the healthy mice, this study provides a toxicological guideline that may expedite the application of CNPs in the clinical settings.

Is nanoparaquat safer than bulk paraquat? An in vitro and in vivo evaluation.

Paraquat (PQ) is an herbicide which has brought some health problems through the production of reactive oxygen species. The increasing interest in the novel formulation of agrochemicals has been aiming to provide safety for non-target organisms. Chitosan is a well-known non-toxic polymer, commonly used in preparing particles via ionotropic gelation. In this study, we prepared PQ nanoparticles (PQNPs) and evaluated their toxicity in vivo and in vitro. PQNPs were prepared and characterized in two forms, with and without the utilization of chitosan. Relative cell survival of PQNPs were studied against bulk PQ in HEK-293. Also, the acute lung injury of PQNP was assessed against treatment with acetylcysteine. Total antioxidant capacity (TAC), lipid peroxidation (LPO), total thiol groups (TTG), and hydroxyproline, along with histological changes were assessed in the lungs. The size, zeta potential, and polydispersity index of the optimum particles were about 157.7 ± 7.03, 22.25 ± 4.52, and 0.701, respectively. The encapsulation efficiency was 65.11 ± 10.45, and the loading percent of PQ was 58.57 ± 2.37. PQNPs showed an initial burst of PQ release followed by a zero-degree pattern. PQNPs displayed lower cell cytotoxicity compared to bulk PQ. LPO, TAC, TTG, and hydroxyproline levels in lungs generally showed more satisfying status in PQNPQs as well. The levels of oxidative status markers indicate lower oxidative damage in lungs and a more desirable response to acetylcysteine treatment, in line with histological changes. PQ loaded in chitosan-alginate particles offers safer characteristics compared with bulk PQ.

Marine polysaccharide laminarin embedded ZnO nanoparticles and their based chitosan capped ZnO nanocomposites: Synthesis, characterization and in vitro and in vivo toxicity assessment.

In the current scenario where more and more products containing nanomaterials are on the technological or pharmaceutical market, it is crucial to have a thorough knowledge of their toxicity before proposing possible applications. A proper analysis of the toxicity of the nanoproducts should include both in vitro and in vivo biological approaches and should consider that the synthesis and purification methods of nanomaterials may affect such toxicity. In the current work, the green synthesis of laminarin embedded ZnO nanoparticles (Lm-ZnO NPs) and their based chitosan capped ZnO nanocomposites (Ch-Lm-ZnO NCmps) is described for the first time. Furthermore, the evaluation of their in vitro cytotoxicity, phytotoxicity, and in vivo (Zebrafish embryo) toxicity was described. First, the green synthesized Lm-ZnO NPs and Ch-Lm-ZnO NCmps were fully physicochemically characterized. Lm-ZnO NPs were greatly agglomerated and had a spindle morphology ranging from 100 to 350 nm, while Ch-Lm-ZnO NCmps had irregular rod shape with flake-like structure clusters randomly aggregated with diverse sizes ranging from 20 to 250 nm. The in vitro cytotoxicity assessment of the green synthesized Lm-ZnO NPs and Ch-Lm-ZnO NCmps was carried out in normal human dermal fibroblasts (HDF) cells and human colon cancer (HT-29) cells by MTT assay. Lm-ZnO NPs and Ch-Lm-ZnO NCmps (0.1-500 µg/mL), significantly inhibited the viability of both cell lines, revealing dose-dependent cytotoxicity. Besides, the Lm-ZnO NPs and Ch-Lm-ZnO NCmps significantly affected seed germination and roots and shoots length of mung (Vigna radiata). Moreover, the zebrafish embryo toxicity of Lm-ZnO NPs and Ch-Lm-ZnO NCmps among the various concentrations used (0.1-500 µg/mL) caused deformities, increased mortality and decreased the survival rate of zebrafish embryo dose-dependently.

Preparation, biocompatibility, and wound healing effects of O-carboxymethyl chitosan nonwoven fabrics in partial-thickness burn model.

This study was aimed at preparing O-carboxymethyl chitosan (CM-CTS) fabrics, and examining the wound healing effects on partial-thickness burn. The functional polysaccharides were produced from chitosan needle-punched nonwovens reacted with chloroacetic acid. Then the biocompatibility and biological functions were evaluated through fibroblast L-929 and SD rats. CM-CTS fabrics were obtained with elongation at break more than 42%, tensile strength reaching 0.65 N/mm2, and water vapor transmission rate about 2600 g/m2∙24 h. Moreover, CM-CTS fabrics could effectively promote the mouse L-929 migration in vitro. CM-CTS fabrics yielded satisfactory results in angiogenesis, collagen deposition, interleukin-6 content, transforming growth factor level and healing rate, which were superior to the positive control and model groups after rats suffering with partial-thickness burn. In conclusion, CM-CTS fabrics possessed proper mechanical properties, air permeability, favorable biocompatibility, acceleration on fibroblasts migration and healing capacity for partial-thickness burn injury, and owned good potential as high-quality wound dressing.

Precision-cut liver slices as a model for assess hepatic cellular response of chitosan-glutathione nanoparticles on cultures treated with zilpaterol and clenbuterol.

Zilpaterol and clenbuterol are two ß-adrenergic agonist drugs used in animal production. Both drugs have anabolic effects with advantages on carcass yield. Meanwhile, zilpaterol is approved for animal feed in authorized countries. Clenbuterol is a banned substance due to the risk of toxicity; however, it is still being used in unknown dose levels in many farm species. Therefore, the use and abuse of these substances should be closely monitored, considering the clenbuterol ability and the not proved yet of zilpaterol to produce reactive oxygen and nitrogen species. Regarding glutathione which is the main intracellular antioxidant plays detoxification functions on liver metabolism; in this work, it is our interest to know the capacity of chitosan-glutathione nanoparticles (CS/GSH-NP) as a complementary source of exogenous GSH to modify the oxide-reduction status on bovine precision-cut liver slice cultures (PCLS) exposed to clenbuterol and zilpaterol. A single drug assay was performed in first instance by adding clenbuterol, zilpaterol, chitosan nanoparticles (CS-NP), and CS/GSH-NP. Then combinate drug assay was carried out by testing clenbuterol and zilpaterol combined with CS-NP or CS/GSH-NP. The results showed that both ß-adrenergic agonists modify in a dose-dependent manner in oxide-reduction response through ROS generation. The activity or content of glutathione peroxidase activity, intracellular GSH, gamma glutamyl-transpeptidase, aspartate aminotrasnferase and alanine aminotrasnferase were modified. The exogenous GSH delivered by nanoparticles could be used to modulate these markers.

Bioactive chitosan biguanidine-based injectable hydrogels as a novel BMP-2 and VEGF carrier for osteogenesis of dental pulp stem cells.

Nowadays, vascularization and mineralization of bone defects is the main bottleneck in the bone regeneration field that is needed to be overcome and developed. Here, we prepared novel in-situ formed injectable hydrogels based on chitosan biguanidine and carboxymethylcellulose loaded with vascular endothelial growth factor (VEGF) and recombinant Bone morphogenetic protein 2 (BMP-2) and studied its influence on osteoblastic differentiation of dental pulp stem cells (DPSCs). The sequential release behavior of the VEGF and BMP-2 from hydrogels adjusted with the pattern of normal human bone growth. MTT assay exhibited that these hydrogels were non-toxic and significantly increased DPSCs proliferation. The Real-time PCR and Western blot analysis on CG11/BMP2-VEGF showed significantly higher gene and protein expression of ALP, COL1α1, and OCN. These results were confirmed by mineralization assay by Alizarin Red staining and Alkaline phosphatase enzyme activity. Based on these evaluations, these hydrogel holds potential as an injectable bone tissue engineering platform.

Chitosan Augments Tetramycin against Soft Rot in Kiwifruit and Enhances Its Improvement for Kiwifruit Growth, Quality and Aroma.

In this study, the co-application of chitosan and tetramycin against kiwifruit soft rot and its effects on the disease resistance, growth, quality and aroma of kiwifruit were investigated. The results show that chitosan could effectively enhance tetramycin against soft rot of kiwifruit with the field control efficacy of 85.33% for spraying chitosan 100 time + 0.3% tetramycin AS 5000-time dilution liquid, which was higher than 80.99% for 0.3% tetramycin AS 5000-time dilution liquid and significantly (p < 0.01) higher than 40.66% for chitosan 100-time dilution liquid. Chitosan could significantly (p < 0.05) improve the promoting effects of tetramycin on total phenolics, total flavonoids, SOD activity of kiwifruit compared to tetramycin during storage for 0-28 days and enhance the disease resistance of kiwifruit. Moreover, the co-application of chitosan and tetramycin was more effective than tetramycin or chitosan alone in enhancing fruit growth, improving fruit quality and increasing fruit aroma. This study highlights that chitosan can be used as an adjuvant to enhance tetramycin against soft rot of kiwifruit and promote tetramycin's improvement for the single fruit volume and weight, vitamin C, soluble sugar, soluble solid, dry matter, soluble protein, titratable acidity and aroma of kiwifruit.

Cell Coding Arrays Based on Fluorescent Glycan Nanoparticles for Cell Line Identification and Cell Contamination Evaluation.

Cell lines are applied on a large scale in the field of biomedicine, but they are susceptible to issues such as misidentification and cross-contamination. This situation is becoming worse over time due to the rapid growth of the biomedical field, and thus there is an urgent need for a more effective strategy to address the problem. As described herein, a cell coding method is established based on two types of uniform and stable glycan nanoparticles that are synthesized using the graft-copolymerization-induced self-assembly (GISA) method, which further exhibit distinct fluorescent properties due to elaborate modification with fluorescent labeling molecules. The different affinity between each nanoparticle and various cell lines results in clearly distinguishable differences in their endocytosis degrees, thus resulting in distinct characteristic fluorescence intensities. Through flow cytometry measurements, the specific signals of each cell sample can be recorded and turned into a map divided into different regions by statistical processing. Using this sensing array strategy, we have successfully identified six human cell lines, including one normal type and five tumor types. Moreover, cell contamination evaluation of different cell lines with HeLa cells as the contaminant in a semiquantitative analysis has also been successfully achieved. Notably, the whole process of nanoparticle fabrication and fluorescent testing is facile and the results are highly reliable.

Chitosan nanoparticles fabricated through host-guest interaction for enhancing the immunostimulatory effect of CpG oligodeoxynucleotide.

CpG oligodeoxynucleotides (CpG ODNs) which can induce innate immune responses and promote adaptive immune responses, are powerful tools in defeating diseases. Here, a novel chitosan nanoparticle (CS-NPs) based on host-guest interaction has been designed for encapsulation and delivery of CpG ODNs for the first time. The CS-NPs exhibited high encapsulation efficiency (98.3%) of CpG ODNs and remained stable in storage under room temperature for at least 7 days. CS-NPs can also prevent CpG ODN diffusion at pH 7. The results of confocal laser scanning microscope images and flow cytometry show that CS-NPs can also be efficiently delivered into living cells. Furthermore, CpG@CS-NPs can increase the immunostimulatory activity of CpG ODNs. Raw 264.7 cells treated with CpG@CS-NPs demonstrated upregulation of both TNF-α and IL-6 cytokines by 13% and 40%, respectively. The newly developed CpG@CS-NPs were thus identified as an efficient system to deliver CpG-ODNs to treat various diseases.

The effect of chitosan addition on cellular uptake and cytotoxicity of ursolic acid niosomes.

This study evaluated the cellular uptake and cytotoxicity of low permeable Ursolic acid (UA) on cancer cells using niosomes composed of span 60 and cholesterol. The results showed that the addition of chitosan increased particle sizes and ζ-potentials. The UA niosomes with chitosan layers had higher cytotoxicity in HeLa cells than without chitosan, however, there was no improvement observed for Huh7it cells. Moreover, chitosan layers improved the cellular uptake, which clathrin-mediated endocytosis may determine the cellular transport of UA niosomes. In conclusion, the addition of chitosan improved cellular uptake and cytotoxicity of UA niosomes in the HeLa cells.

A new antibacterial nano-system based on hematoporphyrin-carboxymethyl chitosan conjugate for enhanced photostability and photodynamic activity.

To promote bactericidal activity, improve photostability and safety, novel antibacterial nanoparticle system based on photodynamic action (PDA) was prepared here through conjugation of photosensitizer hematoporphyrin (HP) onto carboxymethyl chitosan (CMCS) via amide linkage and followed by ultrasonic treatment. The system was stable in PBS (pH 7.4) and could effectively inhibit the photodegradation of conjugated HP because of aggregation-caused quenching effect. ROS produced by the conjugated HP under light exposure could change the structure of nanoparticles by oxidizing the CMCS skeleton and thereby significantly promote the photodynamic activity of HP and its photodynamic activity after 6 h was higher than that of HP·2HCl under the same conditions. Antibacterial experiments showed that CMCS-HP nanoparticles had excellent photodynamic antibacterial activity, and the bacterial inhibition rates after 60 min of light exposure were greater than 97%. Safety evaluation exhibited that the nanoparticles were safe to mammalian cells, showing great potential for antibacterial therapy.

Chitosan-based nanoparticle co-delivery of docetaxel and curcumin ameliorates anti-tumor chemoimmunotherapy in lung cancer.

The application of traditional chemotherapy drugs for lung cancer has obvious limitations, such as toxic side effects, uncontrolled drug-release, poor bioavailability, and drug-resistance. Thus, to address the limitations of free drugs and improve treatment effects, we developed novel T7 peptide-modified nanoparticles (T7-CMCS-BAPE, CBT) based on carboxymethyl chitosan (CMCS), which is capable of targeted binding to the transferrin receptor (TfR) expressed on lung cancer cells and precisely regulating drug-release according to the pH value and reactive oxygen species (ROS) level. The results showed that the drug-loading content of docetaxel (DTX) and curcumin (CUR) was approximately 7.82% and 6.48%, respectively. Good biosafety was obtained even when the concentration was as high as 500 µg/mL. More importantly, the T7-CMCS-BAPE-DTX/CUR (CBT-DC) complexes exhibited better in vitro and in vivo anti-tumor effects than DTX monotherapy and other nanocarriers loaded with DTX and CUR alone. Furthermore, we determined that CBT-DC can ameliorate the immunosuppressive micro-environment to promote the inhibition of tumor growth. Collectively, the current findings help lay the foundation for combinatorial lung cancer treatment.

Fabrication of self-healing pectin/chitosan hybrid hydrogel via Diels-Alder reactions for drug delivery with high swelling property, pH-responsiveness, and cytocompatibility.

Self-healing hydrogels with pH-responsiveness could protect loaded drugs from being destroyed till it arrives to the target. The pectin-based hydrogel is a candidate due to the health benefit, anti-inflammation, antineoplastic activity, nontoxicity, and biospecific degradation, et al. However, the abundant existence of water-soluble branched heteropolysaccharide chains influenced its performance resulting in limitation of the potential. In the present study, we prepared a series of self-healing pectin/chitosan hydrogels via the Diels-Alder reaction. Moreover, pectin/chitosan composite hydrogel was prepared as a contrast. By comparison, it can be seen that the Diels-Alder reaction greatly improved the cross-linking density of hydrogels. The self-healing experiments showed excellent self-healing performance. In different swelling mediums, significant transformation in the swelling ratio was shown, indicating well-swelling property, pH- and thermo-responsiveness. The drug loading and release studies presented high loading efficiency and sustained release performance. The cytotoxicity assay that showed a high cell proliferation ratio manifested great cytocompatibility.

Targeted delivery system using silica nanoparticles coated with chitosan and AS1411 for combination therapy of doxorubicin and antimiR-21.

Herein, a novel targeted delivery system was developed for intracellular co-delivery of doxorubicin (DOX) as a chemotherapeutic drug, antimiR-21 as an oncogenic antagomiR. In this system, DOX was loaded into mesoporous silica nanoparticles (MSNs) and chitosan was applied to cover the surface of MSNs. AS1411 aptamer as targeting nucleolin and antimiR-21 were electrostatically attached onto the surface of the chitosan-coated MSNs and formed the final nanocomplex (AACS nanocomplex). The study of drug release was based on DOX release under pH 7.4 and 5.5. Cellular toxicity and cellular uptake assessments of AACS nanocomplex were carried out in nucleolin positive (C26, MCF-7, and 4T1) and nucleolin negative (CHO) cell lines using MTT assay and flow cytometry analysis, respectively. Also, Anti-tumor efficacy of AACS nanocomplex was evaluated in C26 tumor-bearing mice. Overall, the results show that the combination therapy of DOX and antimiR-21, using AACS nanocomplex, could combat the cancer cell growth rate.

Self-assembled chitosan polymer intercalating peptide functionalized gold nanoparticles as nanoprobe for efficient imaging of urokinase plasminogen activator receptor in cancer diagnostics.

Targeting cell surface receptors for specific drug delivery in cancer has garnered lot of attention. Urokinase plasminogen activator receptor (uPAR), a surface biomarker, is overexpressed on many tumours including breast, colorectal, prostate, and ovarian cancers. Binding of growth factor domain (GFD) of urokinase plasminogen activator (uPA) with uPAR lead to its close conformation, and allow somatomedin B domain (SMB) of vitronectin binding by allosteric modulation. In-silico docking of uPAR with GFD and SMB peptides was performed to identify potential binding affinity. Herein, we report fluorescently labeled peptide functionalized AuNPs with a mixed self-assembled monolayer of intercalating chitosan polymer for efficient targeting and imaging of uPAR-positive cells. The biophysical characterization of nanoconjugates and uPAR-specific targeting was assessed by FACS, cell adhesion, and fluorescence imaging. AuNPs/chitosan/GFD+SMB peptides showed higher uptake as compared to AuNPs/chitosan/GFD, and AuNPs/chitosan/SMB that can be utilized as a tool for molecular targeting and imaging in metastasis.

Biocidal chitosan-magnesium oxide nanoparticles via a green precipitation process.

In the present scenario, the development of eco-friendly multifunctional biocidal substances with low cost and high efficiency, has become the center of focus. This study is, focused on the synthesis of magnesium oxide (MgO) and chitosan-modified magnesium oxide (CMgO) nanoparticles (NPs), via a green precipitation process. In this process, leaves extract of Plumbago zeylanica L was, used as a nucleating agent. The MgO and CMgO NPs exhibit face-centered cubic structures, as confirmed by XRD studies. Morphologically, the FESEM and TEM images showed that the MgO and CMgO NPs were spherical, with an average particle size of ~40±2 and ~37±2 nm, respectively. EDX spectra were used to identify the elemental compositions of the nanoparticles. By using FTIR spectra, the Mg-O stretching frequency of MgO and CMgO NPs were observed at 431 and 435 cm-1, respectively. The photoluminescence (PL) spectra of MgO and CMgO NPs, revealed oxygen vacancies at 499 nm and 519 nm, respectively, due to the active radicals generated, which were responsible for their biocidal activities. The toxicity effects of the nanoparticles developed, on cell viability (antibacterial and anticancer), were measured on the MCF-7 cell line and six different types of gram-negative bacteria. The antibacterial activities of the nanoparticles on: Klebsiella pneumoniae, Escherichia coli, Shigella dysenteriae, Pseudomonas aeruginosa, Proteus vulgaris and Vibrio cholerae bacteria, were studied with the well diffusion method. The MgO and CMgO NPs were tested on breast cancer cell line (MCF-7) via an MTT assay and it proved that CMgO NPs possess higher anticancer properties than MgO NPs. Overall, CMgO NPs showed a higher amount of cytotoxicity for both the bacterial and cancer cells when compared to the MgO NPs. Toxicity studies of fibroblast L929 cells revealed that the CMgO NPs were less harmful to the healthy cells when compared to the MgO NPs. These results suggest that biopolymer chitosan-modified MgO NPs can be used for healthcare industrial applications in order to improve human health conditions.

Comparison of bone wax and chitosan usage on post-sternotomy bone healing.

BACKGROUND: Sternotomy is a standard approach performed in almost every surgical procedure on the heart and mediastinum. Effective hemostasis of the sternum is required to keep the operative field dry, avoid excessive blood transfusions during surgery, and prevent reoperation due to massive postoperative bleeding, which can further increase morbidity and mortality in patients. Bone wax is a mechanical hemostat commonly used after sternotomy and has been known to affect bone healing, trigger chronic inflammatory reactions, and increase the rate of infection. The application of chitosan, which has intrinsic hemostat ability, as hemostatic material is believed to improve bone healing following sternotomy. This study aimed to compare the effectiveness of bone wax and chitosan on bone healing after sternotomy. METHODS: Median sternotomies were performed on 2 groups of New Zealand White rabbits. Each group of 16 animals received either bone wax or chitosan powder as hemostatic material. The degree of bone healing, the number of foreign-body giant cells, and the number of osteoblasts were evaluated after 6 weeks. RESULTS: Radiographs showed that significantly more animals in the chitosan group had total sternal healing (p = 0.033). Histopathology revealed that the number of foreign-body giant cells was significantly less (p = 0.036) and the number of osteoblasts was significantly greater (p < 0.0001) in the group of animals that received chitosan. CONCLUSION: The use of chitosan as hemostatic material can promote better bone healing compared to bone wax.

Exploring the Toxicity, Lung Distribution, and Cellular Uptake of Rifampicin and Ascorbic Acid-Loaded Alginate Nanoparticles as Therapeutic Treatment of Lung Intracellular Infections.

Nanotechnology is a very promising technological tool to combat health problems associated with the loss of effectiveness of currently used antibiotics. Previously, we developed a formulation consisting of a chitosan and tween 80-decorated alginate nanocarrier that encapsulates rifampicin and the antioxidant ascorbic acid (RIF/ASC), intended for the treatment of respiratory intracellular infections. Here, we investigated the effects of RIF/ASC-loaded NPs on the respiratory mucus and the pulmonary surfactant. In addition, we evaluated their cytotoxicity for lung cells in vitro, and their biodistribution on rat lungs in vivo after their intratracheal administration. Findings herein demonstrated that RIF/ASC-loaded NPs display a favorable lung biocompatibility profile and a uniform distribution throughout lung lobules. RIF/ASC-loaded NPs were mainly uptaken by lung macrophages, their primary target. In summary, findings show that our novel designed RIF/ASC NPs could be a suitable system for antibiotic lung administration with promising perspectives for the treatment of pulmonary intracellular infections.