A chitosan-camouflaged nanomedicine triggered by hierarchically stimuli to release drug for multimodal imaging-guided chemotherapy of breast cancer.

Breast cancer remains one of the most intractable diseases, especially the malignant form of metastasis, with which the cancer cells are hard to track and eliminate. Herein, the common known carbohydrate polymer chitosan (CS) was innovatively used as a shelter for the potent tumor-killing agent. The designed nanoparticles (NPs) not only enhance the solubility of hydrophobic paclitaxel (PTX), but also provide a "hide" effect for cytotoxic PTX in physiological condition. Moreover, coupled with the photothermal (PTT) properties of MoS2, results in a potent chemo/PTT platform. The MoS2@PTX-CS-K237 NPs have a uniform size (135 ± 17 nm), potent photothermal properties (η = 31.5 %), and environment-responsive (low pH, hypoxia) and near infrared (NIR) laser irradiation-triggered PTX release. Through a series of in vitro and in vivo experiments, the MoS2@PTX-CS-K237 showed high affinity and specificity for breast cancer cells, impressive tumor killing capacity, as well as the effective inhibitory effect of metastasis. Benefit from the unique optical properties of MoS2, this multifunctional nanomedicine also exhibited favorable thermal/PA/CT multimodality imaging effect on tumor-bearing mice. The system developed in this work represents the advanced design concept of hierarchical stimulus responsive drug release, and merits further investigation as a potential nanotheranostic platform for clinical translation.

Preparation and Evaluation of Chitosan Coated PLGA Nanoparticles Encapsulating Ivosidenib with Enhanced Cytotoxicity Against Human Liver Cancer Cells.

Purpose: Ivosidenib (IVO), an isocitrate dehydrogenase-1 (IDH1) used for treatment of acute myeloid leukemia (AML) and cholangiocarcinoma. However, poor solubility, low bioavailability, high dose and side effects limit clinical application of IVO. Methods: Ivosidenib-loaded PLGA nanoparticles (IVO-PLGA-NPs) and Ivosidenib-loaded chitosan coated PLGA nanoparticles (IVO-CS-PLGA-NPs) were prepared using emulsification and solvent evaporation method for the treatment of liver cancer. Results: The developed IVO-PLGA-NPs were evaluated for their particle size (171.7±4.9 nm), PDI (0.333), ZP (-23.0±5.8 mV), EE (96.3±4.3%), and DL (9.66±1.1%); similarly, the IVO-CS-PLGA-NPs were evaluated for their particle size (177.3±5.2 nm), PDI (0.311), ZP +25.9±5.7 mV, EE (90.8±5.7%), and DL (9.42±0.7%). The chitosan coating of IVO-PLGA-NPs was evidenced by an increase in mean particle size and positive ZP value. Because of the chitosan coating, the IVO-CS-PLGA-NPs showed a more stable and prolonged release of IVO than IVO-PLGA-NPs. In comparison to pure-IVO, the IVO-PLGA-NPs and IVO-CS-PLGA-NPs were found to be more effective against HepG2 cells, with IC50 values for the MTT assay being approximately half of those of pure-IVO. In HepG2 cells, the expressions of caspase-3, caspase-9, and p53 were significantly (p < 0.05) elevated. Conclusion: Overall, these findings suggest that chitosan coating of IVO-PLGA-NPs improves the delivery and efficacy of ivosidenib in liver cancer treatment.

Chitosan/Pomegranate Seed Oil Emulgel Composition as a New Strategy for Dermal Delivery of Hydrocortisone.

Multifunctional delivery systems capable of modulating drug release and exerting adjunctive pharmacological activity have attracted particular attention. Chitosan (CS) and pomegranate seed oil (PO) appear to be attractive bioactive components framing the strategy of complex therapy and multifunctional drug carriers. This research is aimed at evaluating the potential of CS in combination with PO in studies on topical emulgels containing hydrocortisone as a model anti-inflammatory agent. Its particular goal was to distinguish alterations in anti-inflammatory action followed with drug dissolution or penetrative behavior between the designed formulations that differ in CS/PO weight ratio. All formulations favored hydrocortisone release with up to a two-fold increase in the drug dissolution rate within first 5 h as compared to conventional topical preparations. The clear effect of CS/PO on the emulgel biological performance was observed, and CS was found to be prerequisite for the modulation of hydrocortisone absorption and accumulation. In turn, a greater amount of PO played the predominant role in the inhibition of hyaluronidase activity and enhanced the anti-inflammatory effect of preparation E-3. Emulgels showed a negligible reduction in mouse fibroblasts' L929 cell viability, confirming their non-irritancy with skin cells. Overall, the designed formulation with a CS/PO ratio of 6:4 appeared to be the most promising topical carrier for the effective treatment of inflammatory skin diseases among the tested subjects.

Pelvic Organ Prolapse Reconstruction with the Chitosan-Based Novel Haemostatic Agent in Ovine Model-Preliminary Report.

This prospective study aimed to assess the feasibility of chitosan biomaterial and subcutaneous gel implantation in an ovine model, with implications for women with genital prolapse. Twenty-four ewes were divided into four groups (n = 6 per group): chitosan type B, chitosan type C, chitosan unmodified injections, and polypropylene mesh. Ovine models were chosen due to their morphological resemblance to human reproductive organs. Animals were sacrificed after 90 days for macroscopic, pathomorphological, and immunohistochemical analysis. In the chitosan type B group, IL-6 and IL-10 levels decreased after 28 days, while chitosan type C and injection groups exhibited higher IL-6 than IL-10 levels. The polypropylene group displayed the highest IL-6 and lowest IL-10 levels. Histological examination of the polypropylene group revealed no degenerative changes or inflammation, whereas chitosan injection induced local inflammation. Other groups exhibited no degenerative changes. Ewes implanted with chitosan displayed reduced inflammation compared to polypropylene-implanted ewes. Chitosan implantation facilitated vaginal tissue healing, in contrast to polypropylene mesh, which led to extrusion. While chitosan holds promise as an alternative to polypropylene mesh, further research is imperative for comprehensive evaluation. This study suggests the potential of a chitosan biomaterial in pelvic organ prolapse treatment, warranting additional investigation.

Fabrication and antimicrobial properties of novel meropenem-honey encapsulated chitosan nanoparticles against multiresistant and biofilm-forming Staphylococcus aureus as a new antimicrobial agent.

BACKGROUND: Honey exhibits a broad spectrum of antibacterial activity against Gram-positive and Gram-negative bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) ones. Chitosan (Cs) is a mucoadhesive polymer that also has antibacterial properties. Special attention has been paid to the design of polymeric nanoparticles (NPs) as new nano drug delivery systems to overcome bacterial resistance and its problems. OBJECTIVES: The aim of the present study is to synthesize Cs-meropenem NPs with/without honey as an antibiofilm and antibacterial agent to inhibit Staphylococcus aureus. METHODS: This study synthesized meropenem and honey-loaded Cs nanogels and subsequently characterized them by Field Emission Scanning Electron Microscopy (FESEM), Fourier Transform Infrared Spectroscopy (FTIR), and DLS-zeta potential. Using the broth microdilution and crystal violet assays, the antibacterial and antibiofilm activity of meropenem and honey-loaded Cs nanogel, free meropenem, free honey, and free Cs NPs were investigated in vitro against MRSA strains. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) was also used to test the cytotoxicity of several Cs-NPs compound against the HEK-293 regular cell line. RESULTS: The average size of meropenem and honey-Cs-NPs was reported to be 119.885 nm, and encapsulation efficiency was 88.33 ± 0.97 with stability up to 60 days at 4°C. The NPs showed enhanced antibiofilm efficacy against S. aureus at sub-minimum inhibitory concentrations. Additionally, the cytotoxicity of meropenem and honey-encapsulated Cs against the HEK-293 normal cell line was insignificant. CONCLUSIONS: Our findings suggested that meropenem and honey-Cs-NPs might be potential antibacterial and antibiofilm materials.

Sandwich-type electrochemical aptasensor based on hemin-graphite oxide as a signal label and rGO/MWCNTs/chitosan/carbon quantum dot modified electrode for sensitive detection of Acinetobacter baumannii bacteria.

Acinetobacter baumannii (A. baumannii) is a pathogenic bacterium that causes severe infections and its rapid and reliable diagnosis is essential for effective control and treatment. In this study, we present an electrochemical aptasensor based on a signal amplification strategy for the detection of A. baumannii, the high specificity and affinity of the aptamer for the target make it favorable for signal amplification. This allows for a highly sensitive and selective detection of the target. The aptasensor is based on a carbon screen-printed electrode (CSPE) that has been modified with a nanocomposite consisting of multi-walled carbon nanotubes (MWCNTs), reduced graphene oxide (rGO), chitosan (CS), and a synthesized carbon quantum dot (CQD) from CS. Additionally, the self-assembled aptamers were immobilized on hemin-graphite oxide (H-GO) as a signal probe. The composition of the nanocomposite (rGO-MWCNT/CS/CQD) provides high conductivity and stability, facilitating the efficient capture of A. baumannii onto the surface of the aptasensor. Also, aptamer immobilized on Hemin-graphite oxide (H-GO/Aptamer) was utilized as an electrochemical signal reporter probe by H reduction. This approach improved the detection sensitivity and the aptamer surface density for detecting A. baumannii. Furthermore, under optimized experimental conditions, the aptasensor was demonstrated to be capable of detecting A. baumannii with a linear range of (10 - 1 × 107 Colony-forming unit (CFU)/mL) and a limit of detection (LOD) of 1 CFU/mL (σ = 3). One of the key features of this aptasensor is its ability to distinguish between live and dead bacteria cells, which is very important and critical for clinical applications. In addition, we have successfully detected A. baumannii bacteria in healthy human serum and skim milk powder samples provided using the prepared electrochemical aptasensor. The functional groups present in the synthetic CQD, rGO-MWCNT, and chitosan facilitate biomolecule immobilization and enhance stability and activity. The fast electron-transfer kinetics and high conductivity of these materials contribute to improved sensitivity and selectivity. Furthermore, The H-GO/Aptamer composite's large surface area increases the number of immobilized secondary aptamers and enables a more stable structure. This large surface area also facilitates more H loading, leading to signal amplification.

Bioactive and biodegradable cotton fabrics produced via synergic effect of plant extracts and essential oils in chitosan coating system.

Functional antibacterial textile materials are in great demand in the medical sector. In this paper, we propose a facile, eco-friendly approach to the design of antibacterial biodegradable cotton fabrics. Cotton fiber fabrics were enhanced with a chitosan coating loaded with plant extracts and essential oils. We employed Fourier-transform infrared (FTIR) and X-ray photoelectron spectroscopy (XPS), UV-Vis spectrophotometry, optical microscopy, scanning electron microscopy (SEM), and thermogravimetric analysis (TGA) to characterize the color, structure, and thermal properties of the modified fabrics. The fabrics were found to effectively induce growth inhibition of Gram-positive and Gram-negative bacteria, especially when a synergic system of aloe vera extract and cinnamon essential oil was applied in the coating formulation. Additionally, we observed significant color and weight changes after 5, 10, and 20 days in soil biodegradability tests. Given the straightforward modification process and the use of non-toxic natural materials, these innovative bio-based and biodegradable cotton fabrics show great promise as protective antimicrobial textiles for healthcare applications.

Enamel changes of bleached teeth following application of an experimental combination of chitosan-bioactive glass.

BACKGROUND: Considering the extensive use of bleaching agents and the occurrence of side effects such as enamel demineralization, this study aimed to assess the enamel changes of bleached teeth following the experimental application of chitosan-bioactive glass (CH-BG). METHODS: In this in vitro study, CH-BG (containing 66% BG) was synthesized and characterized by Fourier-transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD). Thirty sound human premolars were bleached with 40% hydrogen peroxide, and the weight% of calcium and phosphorus elements of the buccal enamel surface was quantified before and after bleaching by scanning electron microscopy/ energy-dispersive X-ray spectroscopy (SEM, EDX). Depending on the surface treatment of the enamel surface, the specimens were divided into three groups (n = 10): control (no treatment), MI Paste (MI), and CH-BG. Then the specimens were stored in artificial saliva for 14 days. The SEM/EDX analyses were performed again on the enamel surface. Data were analyzed by one-way ANOVA and Tukey's test and a p-value of < 0.05 was considered statistically significant. RESULTS: In all groups, the weight% of calcium and phosphorus elements of enamel decreased after bleaching; this reduction was significant for phosphorus (p < 0.05) and insignificant for calcium (p > 0.05). After 14 days of remineralization, the weight% of both calcium and phosphorus elements was significantly higher compared to their bleached counterparts in both MI and CH-BG groups (p < 0.05). Following the remineralization process, the difference between MI and CH-BG groups was not significant (p > 0.05) but both had a significant difference with the control group in this regard (p < 0.05). CONCLUSIONS: The synthesized CH-BG compound showed an efficacy comparable to that of MI Paste for enamel remineralization of bleached teeth.

Response surface optimization of sludge dewatering process: synergistic enhancement by ultrasonic, chitosan and sludge-based biochar.

Due to the colloidal stability, the high compressibility and the high hydration of extracellular polymeric substances (EPS), it is difficult to efficiently dehydrate sludge. In order to enhance sludge dewatering, the process of ultrasonic (US) cracking, chitosan (CTS) re-flocculation and sludge-based biochar (SBB) skeleton adsorption of water-holding substances to regulate sludge dewaterability was proposed. Based on the response surface method, the prediction model of the specific resistance to filtration (SRF) and sludge cake moisture content (MC) was established. The US cracking time and the dosage of CTS and SBB were optimized. The results showed that the optimal parameters of the three were 5.08 s, 10.1 mg/g dry solids (DS) and 0.477 g/g DS, respectively. Meantime, the SRF and MC were 5.4125 × 1011 m/kg and 76.8123%, which significantly improved the sludge dewaterability. According to the variance analysis, it is found that the fitting degree of SRF and MC model is good, which also confirms that there is significant interaction and synergy between US, CTS and SBB, and the contribution of CTS and SBB is greater. Moreover, the process significantly improves the sludge's calorific value and makes its combustion more durable.

Characterization and Antioxidant and Antibacterial Activities of Carboxymethylated Tamarind Seed Polysaccharide Composite Films Incorporated with ε-Polylysine and Their Application in Fresh-Cut Green Bell Pepper Preservation.

Traditional petroleum-based food-packaging materials have poor permeability, limited active packaging properties, and difficulty in biodegradation, limiting their application. We developed a carboxymethylated tamarind seed polysaccharide composite film incorporated with ε-polylysine (CTPε) for better application in fresh-cut agricultural products. The CTPε films exhibit excellent water vapor barrier properties, but the mechanical properties are slightly reduced. Fourier transform infrared spectroscopy and X-ray diffraction spectra indicate the formation of hydrogen bonds between ε-PL and CTP, leading to their internal reorganization and dense network structure. With the increase of ε-PL concentration, composite films showed notable inhibition of postharvest pathogenic fungi and bacteria, a significant enhancement of 2,2'- azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) radical-scavenging activity, and gradual improvement of wettability performance. Cytotoxicity experiments confirmed the favorable biocompatibility when ε-PL was added at 0.3% (CTPε2). In fresh-cut bell pepper preservation experiments, the CTPε2 coating effectively delayed weight loss and malondialdehyde increase preserved the hardness, color, and nutrients of fresh-cut peppers and prolonged the shelf life of the fresh-cut peppers, as compared with the control group. Therefore, CTPε composite films are expected to be a valuable packaging material for extending the shelf life of freshly cut agricultural products.

Green Synthesis of Zinc Oxide Nanoparticles from Althaea officinalis Flower Extract Coated with Chitosan for Potential Healing Effects on Diabetic Wounds by Inhibiting TNF-α and IL-6/IL-1ß Signaling Pathways.

Background: Diabetes Mellitus is a multisystem chronic pandemic, wound inflammation, and healing are still major issues for diabetic patients who may suffer from ulcers, gangrene, and other wounds from uncontrolled chronic hyperglycemia. Marshmallows or Althaea officinalis (A.O.) contain bioactive compounds such as flavonoids and phenolics that support wound healing via antioxidant, anti-inflammatory, and antibacterial properties. Our study aimed to develop a combination of eco-friendly formulations of green synthesis of ZnO-NPs by Althaea officinalis extract and further incorporate them into 2% chitosan (CS) gel. Method and Results: First, develop eco-friendly green Zinc Oxide Nanoparticles (ZnO-NPs) and incorporate them into a 2% chitosan (CS) gel. In-vitro study performed by UV-visible spectrum analysis showed a sharp peak at 390 nm, and Energy-dispersive X-ray (EDX) spectrometry showed a peak of zinc and oxygen. Besides, Fourier transforms infrared (FTIR) was used to qualitatively validate biosynthesized ZnO-NPs, and transmission electron microscope (TEM) showed spherical nanoparticles with mean sizes of 76 nm and Zeta potential +30mV. The antibacterial potential of A.O.-ZnO-NPs-Cs was examined by the diffusion agar method against Gram-positive (Staphylococcus aureus and Bacillus subtilis) and Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa). Based on the zone of inhibition and minimal inhibitory indices (MIC). In addition, an in-silico study investigated the binding affinity of A.O. major components to the expected biological targets that may aid wound healing. Althaea Officinalis, A.O-ZnO-NPs group showed reduced downregulation of IL-6, IL-1ß, and TNF-α and increased IL-10 levels compared to the control group signaling pathway expression levels confirming the improved anti-inflammatory effect of the self-assembly method. In-vivo study and histopathological analysis revealed the superiority of the nanoparticles in reducing signs of inflammation and wound incision in rat models. Conclusion: These biocompatible green zinc oxide nanoparticles, by using Althaea Officinalis chitosan gel ensure an excellent new therapeutic approach for quickening diabetic wound healing.

Aspirin/amoxicillin loaded chitosan microparticles and polydopamine modified titanium implants to combat infections and promote osteogenesis.

It is known that titanium (Ti) implant surfaces exhibit poor antibacterial properties and osteogenesis. In this study, chitosan particles loaded with aspirin, amoxicillin or aspirin + amoxicillin were synthesized and coated onto implant surfaces. In addition to analysing the surface characteristics of the modified Ti surfaces, the effects of the modified Ti surfaces on the adhesion and viability of rat bone marrow-derived stem cells (rBMSCs) were evaluated. The metabolic activities of Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) biofilms on the modified Ti surfaces were also measured in vitro. Moreover, S. aureus was tested for its antibacterial effect by coating it in vivo. Using water as the droplet medium, the contact angles of the modified Ti surfaces increased from 44.12 ± 1.75° to 58.37 ± 4.15°. In comparison to those of the other groups tested, significant increases in rBMSC adhesion and proliferation were observed in the presence of aspirin + amoxicillin-loaded microspheres, whereas a significant reduction in the metabolic level of biofilms was observed in the presence of aspirin + amoxicillin-loaded microspheres both in vitro and in vivo. Aspirin and amoxicillin could be used in combination to coat implant surfaces to mitigate bacterial activities and promote osteogenesis.

Antibacterial effects of chitosan-based hydrogels containing Trachyspermum ammi essential oil on pathogens isolated from dogs with otitis externa.

BACKGROUND: Growing antibiotic resistance has made treating otitis externa (OE) increasingly challenging. On the other hand, local antimicrobial treatments, especially those that combine essential oils (EOs) with nanoparticles, tend to be preferred over systemic ones. It was investigated whether Ajwain (Trachyspermum ammi) EO, combined with chitosan nanoparticles modified by cholesterol, could inhibit the growth of bacterial pathogens isolated from OE cases in dogs. In total, 57 dogs with clinical signs of OE were examined and bacteriologically tested. Hydrogels of Chitosan were synthesized by self-assembly and investigated. EO was extracted (Clevenger machine), and its ingredients were checked (GC-MS analysis) and encapsulated in chitosan-cholesterol nanoparticles. Disc-diffusion and broth Micro-dilution (MIC and MBC) examined its antimicrobial and therapeutic properties. RESULTS: Staphylococcus pseudintermedius (49.3%) was the most common bacteria isolated from OE cases, followed by Pseudomonas aeruginosa (14.7%), Escherichia coli (13.3%), Streptococcus canis (9.3%), Corynebacterium auriscanis (6.7%), Klebsiella pneumoniae (2.7%), Proteus mirabilis (2.7%), and Bacillus cereus (1.3%). The investigation into the antimicrobial properties of Ajwain EO encapsulated in chitosan nanoparticles revealed that it exhibited a more pronounced antimicrobial effect against the pathogens responsible for OE. CONCLUSIONS: Using chitosan nanoparticles encapsulated with EO presents an effective treatment approach for dogs with OE that conventional antimicrobial treatments have not cured. This approach not only enhances antibacterial effects but also reduces the required dosage of antimicrobials, potentially preventing the emergence of antimicrobial resistance.

The scar-reducing effect of a novel chitosan gel: an in vivo study.

OBJECTIVE: Scar tissue formation, as a normal part of wound healing, initiates in the proliferation phase, continues after the remodelling phase, and may cause an unpleasant appearance or disruption in normal functioning. This study investigated the effects of a topical gel on acute wound healing and reducing scars in a rat model. METHOD: ChitoScar (ChitoTech Company, Iran), a commercial scar-reducing gel based on chitosan, was analysed for antibacterial and antiviral activity through a quantitative suspension test. Its cytotoxic effect was investigated, and then irritation and delayed-type hypersensitivity tests were carried out on rabbits through direct application of the gel. Furthermore, the effect of the chitosan-based gel on wound healing and scar tissue formation was studied in rats with an acute wound in two groups: the treatment group (topical application of the chitosan-based gel); and the control group (without treatment). Histopathological examination was carried out based on the inflammatory cells, collagen fibre, keratinocytes and fibroblasts. RESULTS: Analysis revealed that the chitosan-based gel had no cytotoxicity and caused no erythema, oedema, local or other systemic adverse response. Wound healing occurred earlier in the treatment group, which was a result of a significant increase in re-epithelialisation, angiogenesis, fibroblast population and collagen fibre thickness (p<0.05). In the treatment group, wounds healed completely after 21 days and scars totally disappeared after 28 days, while in the control group, wound healing remained incomplete with distinct scar tissue. CONCLUSION: The results demonstrated the positive effect of the chitosan-based gel on the duration and quality of the wound healing process, as well as minimising the scar tissue formation in this in vivo study.

Development of chitosan lipid nanoparticles to alleviate the pharmacological activity of piperine in the management of cognitive deficit in diabetic rats.

The aim of the present study was to prepare and evaluate Piperine (PP) loaded chitosan lipid nanoparticles (PP-CLNPs) to evaluate its biological activity alone or in combination with the antidiabetic drug Metformin (MET) in the management of cognitive deficit in diabetic rats. Piperine was successfully loaded on CLNPs prepared using chitosan, stearic acid, Tween 80 and Tripolyphosphate (TPP) at different concentrations. The developed CLNPs exhibited high entrapment efficiency that ranged from 85.12 to 97.41%, a particle size in the range of 59.56-414 nm and a negatively charged zeta potential values (- 20.1 to - 43.9 mV). In vitro release study revealed enhanced PP release from CLNPs compared to that from free PP suspensions for up to 24 h. In vivo studies revealed that treatment with the optimized PP-CLNPs formulation (F2) exerted a cognitive enhancing effect and ameliorated the oxidative stress associated with diabetes. PP-CLNPs acted as an effective bio-enhancer which increased the potency of metformin in protecting brain tissue from diabetes-induced neuroinflammation and memory deterioration. These results suggested that CLNPs could be a promising drug delivery system for encapsulating PP and thus can be used as an adjuvant therapy in the management of high-risk diabetic cognitive impairment conditions.

Oral ulcer treatment using human tonsil-derived mesenchymal stem cells encapsulated in trimethyl chitosan hydrogel: an animal model study.

BACKGROUND: Oral ulcers are a common side effect of chemotherapy and affect patients' quality of life. While stem cell transplantation is a potential treatment for oral ulcers, its efficacy is limited as the stem cells tend to remain in the affected area for a short time. This study aims to develop a treatment for oral ulcers by using trimethyl chitosan (TMC) hydrogel with human tonsil-derived stem cells (hTMSCs) to increase the therapeutic effect of stem cells and investigate their effectiveness. METHODS: Animals were divided into four experimental groups: Control, TMC hydrogel, hTMSCs, and hTMSCs loaded in TMC hydrogel (Hydrogel + hTMSCs) (each n = 8). Oral ulcers were chemically induced by anesthetizing the rats followed by injection of dilute acetic acid in the right buccal mucosa. After confirming the presence of oral ulcers in the animals, a single subcutaneous injection of 100 µL of each treatment was applied to the ulcer area. Histological analyses were performed to measure inflammatory cells, oral mucosal thickness, and fibrosis levels. The expression level of inflammatory cytokines was also measured using RT-PCR to gauge therapeutic the effect. RESULTS: The ulcer size was significantly reduced in the TMC hydrogel + hTMSCs group compared to the control group. The stem cells in the tissue were only observed until Day 3 in the hTMSCs treated group, while the injected stem cells in the TMC Hydrogel + hTMSCs group were still present until day 7. Cytokine analysis related to the inflammatory response in the tissue confirmed that the TMC Hydrogel + hTMSCs treated group demonstrated superior wound healing compared to other experimental groups. CONCLUSION: This study has shown that the adhesion and viability of current stem cell therapies can be resolved by utilizing a hydrogel prepared with TMC and combining it with hTMSCs. The combined treatment can promote rapid healing of oral cavity wounds by enhancing anti-inflammatory effects and expediting wound healing. Therefore, hTMSC loaded in TMC hydrogel was the most effective wound-healing approach among all four treatment groups prolonging stem cell survival. However, further research is necessary to minimize the initial inflammatory response of biomaterials and assess the safety and long-term effects for potential clinical applications.

Antibiofilm activity of polyethylene glycol-quercetin nanoparticles-loaded gelatin-N,O-carboxymethyl chitosan composite nanogels against Staphylococcus epidermidis.

BACKGROUND: Biofilms, such as those from Staphylococcus epidermidis, are generally insensitive to traditional antimicrobial agents, making it difficult to inhibit their formation. Although quercetin has excellent antibiofilm effects, its clinical applications are limited by the lack of sustained and targeted release at the site of S. epidermidis infection. OBJECTIVES: Polyethylene glycol-quercetin nanoparticles (PQ-NPs)-loaded gelatin-N,O-carboxymethyl chitosan (N,O-CMCS) composite nanogels were prepared and assessed for the on-demand release potential for reducing S. epidermidis biofilm formation. METHODS: The formation mechanism, physicochemical characterization, and antibiofilm activity of PQ-nanogels against S. epidermidis were studied. RESULTS: Physicochemical characterization confirmed that PQ-nanogels had been prepared by the electrostatic interactions between gelatin and N,O-CMCS with sodium tripolyphosphate. The PQ-nanogels exhibited obvious pH and gelatinase-responsive to achieve on-demand release in the micro-environment (pH 5.5 and gelatinase) of S. epidermidis. In addition, PQ-nanogels had excellent antibiofilm activity, and the potential antibiofilm mechanism may enhance its antibiofilm activity by reducing its relative biofilm formation, surface hydrophobicity, exopolysaccharides production, and eDNA production. CONCLUSIONS: This study will guide the development of the dual responsiveness (pH and gelatinase) of nanogels to achieve on-demand release for reducing S. epidermidis biofilm formation.

Enhancing radioprotection: A chitosan-based chelating polymer is a versatile radioprotective agent for prophylactic and therapeutic interventions against radionuclide contamination.

To mitigate the risk of radioactive isotope dissemination, the development of preventative and curative measures is of particular interest. For mass treatment, the developed solution must be easily administered, preferably orally, with effective, nontoxic decorporating properties against a wide range of radioactive isotopes. Currently, most orally administered chelation therapy products are quickly absorbed into the blood circulation, where chelation of the radioactive isotope is a race against time due to the short circulation half-life of the therapeutic. This report presents an alternative therapeutic approach by using a functionalized chitosan (chitosan@DOTAGA) with chelating properties that remains within the gastrointestinal tract and is eliminated in feces, that can protect against ingested radioactive isotopes. The polymer shows important in vitro chelation properties towards different metallic cations of importance, including (Cs(I), Ir(III), Th(IV), Tl(I), Sr(II), U(VI) and Co(II)), at different pH (from 1 to 7) representing the different environments in the gastrointestinal tract. An in vivo proof of concept is presented on a rodent model of uranium contamination following an oral administration of Chitosan@DOTAGA. The polymer partially prevents the accumulation of uranium within the kidneys (providing a protective effect) and completely prevents its uptake by the spleen.

Effects of solid lipid nanocarrier containing methyl urolithin A by coating folate-bound chitosan and evaluation of its anti-cancer activity.

BACKGROUND: Nanotechnology-based drug delivery systems have received much attention over the past decade. In the present study, we synthesized Methyl Urolithin A-loaded solid lipid nanoparticles decorated with the folic acid-linked chitosan layer called MuSCF-NPs and investigated their effects on cancer cells. METHODS: MuSCF-NPs were prepared using a high-pressure homogenization method and characterized using FTIR, FESEM, DLS, and zeta potential methods. Drug encapsulation was assessed by spectrophotometry and its cytotoxic effect on various cancer cells (MDA-MB231, MCF-7, PANC, AGS, and HepG2) by the MTT method. Antioxidant activity was assessed by the ABTS and DPPH methods, followed by expression of genes involved in oxidative stress and apoptosis by qPCR and flow cytometry. RESULTS: The results showed the formation of monodisperse and stable round nanoparticles with a size of 84.8 nm. The drug loading efficiency in MuSCF-NPs was reported to be 88.6%. MuSCF-NPs exhibited selective cytotoxicity against MDA-MB231 cells (IC50 = 40 µg/mL). Molecular analysis showed a significant increase in the expression of Caspases 3, 8, and 9, indicating that apoptosis was occurring in the treated cells. Moreover, flow cytometry results showed that the treated cells were arrested in his SubG1 phase, confirming the pro-apoptotic effect of the nanoparticles. The results indicate a high antioxidant effect of the nanoparticles with IC50 values ​​of 45 µg/mL and 1500 µg/mL against ABTS and DPPH, respectively. The reduction of catalase gene expression confirmed the pro-oxidant effect of nanoparticles in cancer cells treated at concentrations of 20 and 40 µg/mL. CONCLUSIONS: Therefore, our findings suggest that the MuSCF-NPs are suitable candidates, especially for breast cancer preclinical studies.

Levofloxacin loaded chitosan and poly-lactic-co-glycolic acid nano-particles against resistant bacteria: Synthesis, characterization and antibacterial activity.

BACKGROUND: With the global increase in antibacterial resistance, the challenge faced by developing countries is to utilize the available antibiotics, alone or in combination, against resistant bacterial strains. We aimed to encapsulate the levofloxacin (LVX) into polymeric nanoparticles using biodegradable polymers i.e. Chitosan and PLGA, estimating their physicochemical characteristics followed by functional assessment as nanocarriers of levofloxacin against the different resistant strains of bacteria isolated from biological samples collected from tertiary care hospital in Lahore, Pakistan. METHODS: LVX-NPs were synthesized using ion gelation and double emulsion solvent-evaporation method employing chitosan (CS) and poly-lactic-co-glycolic acid (PLGA), characterized via FTIR, XRD, SEM, and invitro drug release studies, while antibacterial activity was assessed using Kirby-Bauer disc-diffusion method. RESULTS: Data revealed that the levofloxacin-loaded chitosan nanoparticles showed entrapment efficiency of 57.14% ± 0.03 (CS-I), 77.30% ± 0.08(CS-II) and 87.47% ± 0.08 (CS-III). The drug content, particle size, and polydispersity index of CS-I were 52.22% ± 0.2, 559 nm ± 31 nm, and 0.030, respectively, whereas it was 66.86% ± 0.17, 595 nm ± 52.3 nm and 0.057, respectively for CS-II and 82.65% ± 0.36, 758 nm ± 24 nm and 0.1, respectively for CS-III. The PLGA-levofloxacin nanoparticles showed an entrapment efficiency of 42.80% ± 0.4 (PLGA I) and 23.80% ± 0.4 (PLGA II). The drug content, particle size and polydispersity index of PLGA-I were 86% ± 0.21, 92 nm ± 10 nm, and 0.058, respectively, whereas it was 52.41% ± 0.45, 313 nm ± 32 nm and 0.076, respectively for PLGA-II. The XRD patterns of both polymeric nanoparticles showed an amorphous nature. SEM analysis reflects the circular-shaped agglomerated nanoparticles with PLGA polymer and dense spherical nanoparticles with chitosan polymer. The in-vitro release profile of PLGA-I nanoparticles showed a sustained release of 82% in 120 h and it was 58.40% for CS-III. Both types of polymeric nanoparticles were found to be stable for up to 6 months without losing any major drug content. Among the selected formulations, CS-III and PLGA-I, CS-III had better antibacterial potency against gram+ve and gram-ve bacteria, except for K. pneumonia, yet, PLGA-I demonstrated efficacy against K. pneumonia as per CSLI guidelines. All formulations did not exhibit any signs of hemotoxicity, nonetheless, the CS-NPs tend to bind on the surface of RBCs. CONCLUSION: These data suggested that available antibiotics can effectively be utilized as nano-antibiotics against resistant bacterial strains, causing severe infections, for improved antibiotic sensitivity without compromising patient safety.