Chitosan nanoparticles loaded with royal jelly: Characterization, antioxidant, antibacterial activities and in vitro digestion.

Nano-embedding has appeared as a feasible technology to improve the high-quality utilization of royal jelly (RJ). Therefore, the ionic gelation method was proposed to prepared chitosan nanoparticles loaded with royal jelly (RJNPs) and the characterization and biological activity of RJNPs were evaluated in this study. Fourier-transform infrared spectroscopy, differential scanning calorimetry and X-ray diffraction results showed that the methyl and methylene groups of royal jelly combine with the amino groups of chitosan (CS) to become an amorphous polymer. In addition, the 48.68 % encapsulation efficiency and 31.90 % loading capacity were obtained under the optimal ratio of 1:1 RJ to CS, and the average particle size was <500 nm. The antioxidant activity of RJNPs gradually increased with the increase of the RJ proportion. Interestingly, the antibacterial activity on gram-positive bacteria was better than gram-negative bacteria. Most important, RJNPs exhibited better stability and digestibility rather than single RJ. Overall, these findings indicated that RJ can be embedded in chitosan, and RJNPs exhibited good thermal stability, antioxidant activity, antibacterial activities and bioavailability, which was important for the development and application of the high-quality utilization of RJ.

Dihydroquercetin nanoparticles nasal gel is a promising formulation for amelioration of Alzheimer's disease.

Dihydroquercetin is a natural flavonoid with anti-inflammatory, antioxidant, and neuroprotective activities. Dihydroquercetin exhibits a great neuroprotector promise in Alzheimer's disorder via preventing the aggregation of amyloid-beta-peptide-Aß(1-42). The goal of the study was to create dihydroquercetin-loaded-chitosan nanoparticles (DHQ-CS NPs) loaded to a mucoadhesive, thermosensitive in-situ gel for direct nasal administration to cure Alzheimer's disorder. Loading drug in chitosan nanoparticles and incorporation into thermosensitive gel enhanced residence time and reduced mucociliary-clearance. Different in-vitro-physicochemical-characteristics of gels and nanoparticles-characterization were used to evaluate the formulations. The therapeutic effectiveness of DHQ-CS NPs gel was evaluated behaviorally, biochemically and histopathologically in Alzheimer's-rat-model compared to intranasal DHQ gel. The small particles-size was obtained = 235.3 nm of DHQ-CS NPs. The DHQ-CS NPs gel demonstrated a greater release rate compared to the raw DHQ gel. Additionally, the nasal-administration of the DHQ-CS NPs gel showed better In-vivo results compared to DHQ gel, through improvement of memory and learning deficits and also the exploratory behavior and new object memory in streptozotocin induced-Alzheimer rats. Biochemically, the intranasal DHQ-CS NPs gel, showed reduced both Aß-protein formation and tau protein hyperphosphorylation, inhibition of acetylcholine esterase activity and oxidative stress in the brain with increase of total antioxidants in the brain and serum, compared to DHQ gel. Histopathologically, the DHQ-CS NPs nasal gel produced improvement in the hippocampal and cerebral cortex structures, being comparable to the normal group. Consequently, the intranasal DHQ-CS NPs loaded in-situ gel seems to be a promising therapeutic formulation for Alzheimer's disease medication.

Impacts of dietary supplementation of chitosan nanoparticles on growth, carcass traits nutrient digestibility, blood biochemistry, intestinal microbial load, and meat quality of broilers.

This study explores the impact of chitosan nanoparticles (CNP) on the performance, nutrient digestibility, blood biochemical, immunity, microbial load, carcass traits, and meat attributes of broilers. A total of 200 7-d-old Cobb chicks were distributed to 4 groups, each replicated 5 times, with 10 birds in each replicate. The experimental diets were as follows: First group was fed a basal diet only (control); 2nd, 3rd, and 4th groups received a basal diet supplemented with 0.2, 0.3, and 0.4 g CNP/kg of feed, respectively. Results showed that the body weight (BW) and body weight gain significantly improved (P < 0.05) in the birds belonging to the 0.4 CNP group compared to the other groups. The best feed efficiency (feed conversion ratio [FCR]) was found in the group supplemented with a 0.4-g CNP/kg diet. The digestibility coefficients for dry matter and crude protein were significantly higher, and ether extract was significantly lower in the 0.4 g CNP/kg group than in other groups (P < 0.05). Broiler birds of the 0.4 CNP group had significantly (P < 0.05) reduced serum cholesterol, AST, and ALT levels. The humoral immunity (increased serum IgG and IgM levels) tended to improve in birds fed 0.3 and 0.4 g CNP/kg of feed. Compared to the control, total bacterial load and coliform count decreased significantly (P < 0.05) by supplementing 0.4 g CNP in the diet. The dressing weight, breast weight, and abdominal fat % were altered in birds receiving dietary 0.4 g CNP/kg. The treatment with CNP at 0.4 g/kg feed enhanced the broiler meat quality by increasing the values for water holding capacity, ABTS [2, 2'-azinobis (3-ethylbenzothiazoline-6-sulfonic acid)], DPPH (2,2-diphenyl-1-picrylhydrazyl) while reducing the thiobarbituric acid reactive substances (TBARS) value. Based on the results above, it could be concluded that CNP supplementation at 0.4 g/kg is recommended as a beneficial feed additive for broiler chickens.

Modulation of Inflammation in McCoy Cells by Zinc Nanoparticles Conjugated With ß-Chitosan.

INTRODUCTION: This study investigated biosynthetically derived ß-chitosan-derived zinc nanoparticles (ß-Ch-Zn NPs) for their potential anti-inflammatory properties on McCoy cells. ß-Ch-Zn NPs were synthesized using a green chemistry approach, and their characterization confirmed successful synthesis, appropriate size, and morphology. The study aimed to evaluate the cytotoxicity of ß-Ch-Zn NPs and their effects on inflammatory responses in McCoy cells stimulated with lipopolysaccharide (LPS). METHODS:  ß-Ch-Zn NPs were synthesized and characterized using Fourier-transform infrared spectroscopy (FTIR), ultraviolet-visible spectroscopy (UV-Vis) spectroscopy, and X-ray diffraction (XRD) to confirm their structural and morphological properties. The cytotoxicity of ß-Ch-Zn NPs was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay at various concentrations to determine safe doses for subsequent experiments. To induce inflammation, McCoy cells were pretreated with ß-Ch-Zn NPs at different concentrations before LPS stimulations. Gene expression analysis using quantitative real-time polymerase chain reaction was performed to measure the messenger RNA (mRNA) levels of proinflammatory cytokine. RESULTS: FTIR, UV-Vis spectroscopy, and XRD confirmed the successful synthesis of ß-Ch-Zn NPs with the desired size and morphology. The MTT assay demonstrated concentration-dependent cytotoxicity of ß-Ch-Zn NPs, indicating safety for cellular studies. Pretreatment with ß-Ch-Zn NPs significantly downregulated the mRNA expression of proinflammatory cytokines. The nanoparticles effectively downregulate proinflammatory cytokines and promote anti-inflammatory pathways, as evidenced by the significant reduction in interleukin (IL)-2, IL-6, hypoxia-inducible factor, and nuclear factor kappa B expression in a dose-dependent manner. CONCLUSIONS: This study demonstrated that biosynthetically derived ß-Ch-Zn NPs exhibit potent anti-inflammatory effects in McCoy cells. These findings underscore the therapeutic potential of ß-Ch-Zn NPs for treating inflammatory conditions and support further investigation into their in vivo efficacy and safety.

Exploring chitosan nanoparticles for enhanced therapy in neurological disorders: a comprehensive review.

Chitosan nanoparticles have emerged as a promising therapeutic platform for treating neurological disorders due to their biocompatibility, biodegradability, and ease of functionalization. One of the significant challenges in treating neurological conditions is overcoming the blood-brain barrier (BBB), which restricts the effective delivery of therapeutic agents to the brain. Addressing this barrier is crucial for the successful treatment of various neurological diseases, including Alzheimer's disease, Parkinson's disease, epilepsy, migraine, psychotic disorders, and brain tumors. Chitosan nanoparticles offer several advantages: they enhance drug absorption, protect drugs from degradation, and enable targeted delivery. These properties open new possibilities for non-invasive therapies for neurological conditions. Numerous studies have highlighted the neuroprotective potential of chitosan nanoparticles, demonstrating improved outcomes in animal models of neurodegeneration and neuroinflammation. Additionally, surface modifications of these nanoparticles allow for the attachment of specific ligands or molecules, enhancing the precision of drug delivery to neuronal cells. Despite these advancements, several challenges persist in the clinical translation of chitosan nanoparticles. Issues such as large-scale production, regulatory hurdles, and the need for further research into long-term safety must be addressed. This review explores recent advancements in the use of chitosan nanoparticles for managing neurological disorders and outlines potential future directions in this rapidly evolving field of research.

Analysis of the mechanisms underlying the anticancer and biological activity of retinoic acid and chitosan nanoparticles containing retinoic acid.

Retinoic acid (RA) has been shown in earlier investigations to have anticancer properties in various cancer cells. RA's effect on breast cancer treatment remains uncertain, though. This study investigated whether RA and chitosan nanoparticles (NPs) loaded with RA could be harmful to the MCF-7 cell line. In this study, NPs with RA were used in characterization tests. Using ELISA kits, the amounts of 8-okso-2'-deoksiguanozin (8-oxo-dG), BCL-2, Bcl-2-Associated X-protein (Bax), cleaved Poly (ADP-ribose) polymerases (PARP), total oxidant and antioxidant, and cleaved caspase-3 capacities were determined. The analysis of chitosan NPs showed that their drug-release profile, encapsulation efficiency (EE), and particle size were suitable for cell culture experiment. The EE value of NPs including RA was calculated as 83.32 ± 0.04%. The IC50 value for RA was 2.89 ± 0.03 µg/mL, while the IC50 value for RA-loaded NPs was significantly lower at 2.28 ± 0.02 µg/mL. In ELISA testing, RA and chitosan NPs containing RA at a concentration of 2 µg/mL dramatically increased the concentrations of total oxidant, cleaved caspase-3. Cleaved caspase-3 levels were quantified as 614.90 ± 3.40 pg/mg protein in the control group, 826.37 ± 5.82 pg/mg protein in RA-treated cells, and 863.52 ± 4.32 pg/mg protein in RA-NP-treated cells. Interestingly, no substantial variations were observed in the levels of the anti-apoptotic protein BCL-2. Overall, studies revealed that RA and RA-NPs promoted apoptosis in MCF-7 cells by upregulating the expression of pro-apoptotic proteins Bax, cleaved caspase-3, and cleaved PARP.

Formulating a TMEM176B blocker in chitosan nanoparticles uncouples its paradoxical roles in innate and adaptive antitumoral immunity.

The immunoregulatory cation channel TMEM176B plays a dual role in tumor immunity. On the one hand, TMEM176B promotes antigen cross-presentation to CD8+ T cells by regulating phagosomal pH in dendritic cells (DCs). On the other hand, it inhibits NLRP3 inflammasome activation through ionic mechanisms in DCs, monocytes and macrophages. We speculated that formulating BayK8644 in PEGylated chitosan nanoparticles (NP-PEG-BayK8644) should slowly release the compound and by that mean avoid cross-presentation inhibition (which happens with a fast 30 min kinetics) while still triggering inflammasome activation. Chitosan nanocarriers were successfully obtained, exhibiting a particle size within the range of 200 nm; they had a high positive surface charge and a 99 % encapsulation efficiency. In in vitro studies, NP-PEG-BayK8644 did not inhibit antigen cross-presentation by DCs, unlike the free compound. The NP-PEG-BayK8644 activated the inflammasome in a Tmem176b-dependent manner in DCs. We administered either empty (eNP-PEG) or NP-PEG-BayK8644 to mice with established tumors. NP-PEG-BayK8644 significantly controlled tumor growth and improved mice survival compared to both eNP-PEG and free BayK8644 in melanoma and lymphoma models. This effect was associated with enhanced inflammasome activation by DCs in the tumor-draining lymph node and infiltration of the tumor by CD8+ T cells. Thus, encapsulation of BayK8644 in chitosan NPs improves the anti-tumoral properties of the compound by avoiding inhibition of antigen cross-presentation.

Chitosan nanoparticles encapsulated Piper betle essential oil alleviates Alzheimer's disease associated pathology in Caenorhabditis elegans.

A multifaceted approach in treating Alzheimer's disease (AD), a neurodegenerative condition that poses health risks in the aging population is explored in this investigation via encapsulating Piper betle essential oil (PBEO) in chitosan nanoparticles (ChNPs) to improve solubility and efficacy of PBEO. PBEO-ChNPs mitigated AD-like features more effectively than free PBEO by delaying paralysis progression and reducing serotonin hypersensitivity, ROS levels, Aß deposits, and neurotoxic Aß-oligomers in the Caenorhabditis elegans AD model. PBEO-ChNPs significantly improved lifespan, neuronal health, healthspan, cognitive function, and reversed deficits in chemotaxis and reproduction. PBEO-ChNPs also induced stress response genes daf-16, sod-3, and hsp-16.2. The participation of the DAF-16 pathway in reducing Aß-induced toxicity was confirmed by daf-16 RNAi treatment, and upregulation of autophagy genes leg-1, unc-51, and bec-1 was noted. This study is the first to demonstrate an alternative biopolymeric nanoformulation with natural PBEO and chitosan, in mitigating AD and its associated symptoms.

Rhein-loaded chitosan nanoparticles for treatment of MRSA-infected wound.

The multi-drug resistance of methicillin-resistant Staphylococcus aureus (MRSA) and complex wound microenvironment challenge the repair of MRSA infected wound. Herein, in this study, α-tocopherol modified glycol chitosan (TG) nanoparticles encapsulated with phytochemical rhein (Rhein@TG NPs) were prepared for comprehensive anti-infection and promotion of MRSA infected wound healing. Rhein@TG NPs could not only specifically release rhein in the infection site in response to low pH and lipase of infectious microenvironment, but also up-regulated M1 macrophage polarization in the infection stage, thus achieving synergistically bacterial elimination with low possibility of developing resistance. Additionally, the NPs reduced the levels of pro-inflammatory factors in the post-infection stage, scavenged the ROS, promoted cell migration and angiogenesis, which significantly improved the microenvironment of infected wound healing. Therefore, this antibiotic-free NPs enabling anti-infection and promotion of wound healing provides a new and long-term strategy for the treatment of MRSA infected wound.

Formulation and optimization of surfactant-modified chitosan nanoparticles loaded with cefdinir for novel topical drug delivery: Elevating wound healing efficacy with enhanced antibacterial properties.

Burn wounds remain a significant global health concern, frequently exacerbated by bacterial infections that hinder healing and raise morbidity rates. Cefdinir, a third-generation cephalosporin antibiotic, is used to treat various conditions, but it has limitations such as low water solubility, limited bioavailability, and a short biological half-life. This study aimed to fabricate and optimize novel surfactant-based Cefdinir-loaded chitosan nanoparticles (CFD-CSNPs) for enhancing topical CFD delivery and efficacy in burn healing. Box-Behnken Design (BBD) was employed to develop optimized CFD-CSNPs using Design Expert® software, where the independent factors were chitosan concentration, chitosan: sodium tripolyphosphate ratio, pH, and surfactant type. Particle size PS, zeta potential ZP, Polydispersity index PDI, and entrapment efficiency EE% were evaluated as dependent factors. CFD-CSNPs were produced using the ionic gelation method. The optimized formula was determined and then examined for further in vitro and in vivo assessments. The optimized CFD-CSNPs exhibited acceptable PS, PDI, and ZP values. The EE% of CFD from CSNPs reached 57.89 % ± 1.66. TEM analysis revealed spherical morphology. In vitro release studies demonstrated a biphasic release profile up to (75.5 % ± 3.8) over 48 hrs. The optimized CFD-CSNPs showed improved antimicrobial efficacy against the tested microorganisms, exhibiting superior performance for both biofilm prevention and eradication. Enhanced wound healing activity was achieved by the optimized CFD-CSNPs in both in vitro and in vivo studies as confirmed by scratch wound assay and skin burn mice model. The current study advocates the efficacy of the innovative topical application of CFD-CSNPs for wound healing purposes and treatment of wound infections.

A two-in-one molybdenum disulfide-chitosan nanoparticles system for activating plant defense mechanisms and reactive oxygen species to treat Citrus Huanglongbing.

Citrus Huanglongbing (HLB) poses an enormous challenge to Citrus cultivation worldwide, necessitating groundbreaking interventions beyond conventional pharmaceutical methods. In this study, we propose molybdenum disulfide-chitosan nanoparticles (MoS2-CS NPs) through electrostatic adsorption, preserving the plant-beneficial properties of molybdenum disulfide (MoS2), while enhancing its antibacterial effectiveness through chitosan modification. MoS2-CS NPs exhibited significant antibacterial efficacy against RM1021, and the closest relatives to Candidatus Liberibacter asiaticus (CLas), Erwinia carotovora, and Xanthomonas citri achieved survival rates of 7.40 % ± 1.74 %, 8.94 % ± 1.40 %, and 6.41 % ± 0.56 %, respectively. In vivo results showed, CLas survival rate of 10.42 % ± 3.51 %. Furthermore, treatment with MoS2-CS NPs resulted in an increase in chlorophyll and carotenoid content. Concomitantly, a significant reduction in malondialdehyde (MDA), soluble sugar, hydrogen peroxide (H2O2), and starch contents was also observed. Mechanistically, MoS2-CS NPs enhanced the activity of antioxidant-related enzymes by upregulating the expression of antioxidant genes, thereby galvanizing the antioxidant system to alleviate oxidative stress. Collectively, this dual functionality-combining direct antibacterial action with the activation of plant defense mechanisms-marks a promising strategy for managing Citrus Huanglongbing and suggests potential agricultural applications for MoS2-based antibacterial treatments.

Comparative evaluation of antimicrobial efficacy of chitosan nanoparticles and calcium hydroxide against endodontic biofilm of Enterococcus faecalis: An in vitro study.

Aim: The aim of the study was to assess and evaluate the antimicrobial effectiveness of chitosan nanoparticles (CSNPs) with calcium hydroxide in the elimination of Enterococcus faecalis. Materials and Methods: Using the broth microdilution method, the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of calcium hydroxide and CSNPs were measured. The antibiofilm effect of calcium hydroxide and CSNPs against E. faecalis biofilm was qualitatively analyzed using a crystal violet assay. A 7-day-old biofilms of E. faecalis grown on dentine discs were assigned to the following three groups (n = 11 dentine discs), normal saline (group I), calcium hydroxide (group II), and CSNPs (group III). Quantification of live and dead cells using confocal microscopy was done to evaluate the antibiofilm efficacy of the medicaments included in the study. Results: MIC of calcium hydroxide and CSNPs against E. faecalis was observed at 2.5 mg/mL and 0.31 mg/mL, respectively. MBC of calcium hydroxide and CSNPs was observed at 2.5 mg/mL and 0.31 mg/mL, respectively. Using Crystal Violet (CV) assay, calcium hydroxide and CSNPs showed biofilm inhibition at concentrations of 2.5 mg/mL and 0.625 mg/mL, respectively. Confocal laser scanning microscopy analysis found that both calcium hydroxide and CSNPs showed a significant decrease in viable cells at their MBC values compared to the control group's normal saline. CSNPs showed a significantly lower percentage of live cells than calcium hydroxide (P < 0.05). Conclusion: The study results reveal that the antimicrobial efficacy of CSNPs is better than calcium hydroxide and normal saline against E. faecalis biofilm.

Metformin-loaded chitosan nanoparticles augment silver nanoparticle-induced radiosensitization in breast cancer cells during radiation therapy.

Recent research has focused on enhancing tumor response to radiation therapy using radiosensitizers to increase radiation absorption by cancerous tissues. This study utilized silver nanoparticles (AgNPs) as radiation sensitizers and chitosan as a nanocarrier to deliver metformin to breast cancer cells. Metformin-loaded chitosan nanoparticles (Met NPs) and AgNPs were synthesized and characterized. MCF-7 breast cancer cells were pretreated with Met NPs, followed by treatment with AgNPs and irradiation with X-rays at 2, 4, and 8 Gy doses. Cellular cytotoxicity, apoptosis, DNA damage, and 3D spheroid formation were evaluated. The synthesized Met NPs and AgNPs had average diameters of 51.5 ± 9.4 nm and 3.02 ± 0.03 nm, respectively. Cellular cytotoxicity assessment revealed the highest cytotoxicity in MCF-7 cells pretreated with Met NPs, treated with AgNPs, and irradiated with 8 Gy. Flow cytometry analysis demonstrated a 67.58 % apoptosis rate in cells pretreated with Met NPs, compared to 30.42 % in cells pretreated with plain metformin. DAPI staining revealed a 1.8-fold increase in DNA damage in cells pretreated with Met NPs and Ag NPs upon exposure to radiation. The 3D spheroid culture model confirmed a 60 % enhancement in the radiosensitivity of breast cancer cells in the presence of Met NPs and Ag NPs. The combination of Met NPs and Ag NPs represents a promising strategy to improve the therapeutic efficacy of radiation therapy for breast cancer treatment. The delivery of metformin can potentiate the radiosensitizing effects of Ag NPs, offering a novel approach to enhance cancer cells' response to radiation.

Nanoencapsulation of active compounds in chitosan by ionic gelation: Physicochemical, active properties and application in packaging.

The ionic gelation technique using chitosan to encapsulate active compounds has received lots of attention in the literature due to its ease-of-use and known biodegradability, biocompatibility and antimicrobial properties of the polymer. In this review, main studies from the last five years involving encapsulation of active compounds (natural and commercial/synthetic) are brought together in order to understand the encapsulation mechanisms of components with chitosan as well as the physical, chemical and morphological properties of the resulting particles. The application of these nanostructures in polymeric films was then investigated, since additives for packaging are an attractive premise and have only recently started being studied in the literature. Herein, comparisons are made between free and encapsulated bioactive compounds in different film matrices, as well as the effect of this activation on structure. Finally, this work details the mechanisms involved in the production of chitosan nanoparticles with active compounds and encourages new studies to focus on their application in packaging.

Synthesis of Ganoderic Acids Loaded Zein-Chitosan Nanoparticles and Evaluation of Their Hepatoprotective Effect on Mice Given Excessive Alcohol.

Ganoderma lucidum, used in East Asia for its health benefits, contains ganoderic acids (GA) which have various pharmacological activities but are limited by poor water solubility and low oral bioaccessibility. This study synthesized and characterized ganoderic acids loaded zein-chitosan nanoparticles (GA-NPs), and investigated its advantages in alleviating alcoholic liver injury (ALI) in mice model. The GA-NPs demonstrated high encapsulation efficiency (92.68%), small particle size (177.20 nm), and a +29.53 mV zeta potential. The experimental results of alcohol-induced liver injury mouse model showed that GA-NPs significantly improved liver metabolic function, reduced alcohol-induced liver oxidative stress in liver by decreasing lactate dehydrogenase activity and malondialdehyde level, while increasing the activities of liver antioxidant enzymes and alcohol dehydrogenase. Moreover, GA-NPs were favorable to ameliorate intestinal microbiota dysbiosis in mice exposed to alcohol by increasing the proportion of probiotics such as Romboutsia, Faecalibaculum, Bifidobacterium and Turicibacter, etc., which were highly correlated with the improvement of liver function. Furthermore, GA-NPs modulated the mRNA expression related to ethanol metabolism, oxidative stress and lipid metabolism. Conclusively, this study revealed that GA-NPs have stronger hepatoprotective effects than non-encapsulated ganoderic acids on alleviating ALI by regulating intestinal microbiota and liver metabolism.

5-Fluorouracil-loaded green chitosan nanoparticles/ guar gum nanocomposite hydrogel in controlled drug delivery.

In recent years nanotechnologies have been applied to human health with promising results, especially in the field of drug delivery. Polymeric nanoparticles (NPs) have garnered much importance in controlled drug delivery owing to their size. Chitosan (Cs) is a well-recognized biopolymer and Cs NPs have been widely explored in drug delivery. Nonetheless, reports pertaining to green synthesis of Cs NPs are scarce. Thus, in this study, green synthesis of Cs NPs was accomplished from raw mango peel extract. Spherical Cs NPs with positively charged surface of 33.4 mV was accomplished by this process. Cs NPs, in varied content, were integrated in a guar gum network matrix resulting in a nanocomposite hydrogel. The mechanical and thermal stability of the hydrogel improved upon addition of Cs NPs. The hydrogel exhibited smart swelling, good antioxidant and anti-inflammatory propensities. Cs NPs encapsulating 5-Fluorouracil demonstrated a controlled release drug profile in the colorectum and the kinetics implied the anomalous nature of drug release mechanism. The exposure of the drug-loaded nanocomposite hydrogel displayed improved anticancer effects in HT-29 colon cancer cells. Taken altogether, this study puts forth the greater efficacy of Cs NPs in controlled drug delivery for anticancer therapy.

Antibody conjugated targeted nanotherapy epigenetically inhibits calpain-mediated mitochondrial dysfunction to attenuate Parkinson's disease.

Many neurodegenerative and psychiatric malignancies like Parkinson' disease (PD) originate from an imbalance of 17ß-Estradiol (E2) in the human brain. However, the peripheral side effects of the usage of E2 for PD therapy and less understanding of the molecular mechanism hinder establishing its neurotherapeutic potential. In the present work, systemic side effects were overcome by targeted delivery using Dopamine receptor D3 (DRD3) conjugated E2-loaded chitosan nanoparticles (Ab-ECSnps) that showed a promising delivery to the brain. E2 is a specific calpain inhibitor that fosters neurodegeneration by disrupting mitochondrial function, while B-cell-specific Moloney murine leukemia virus integration region 1 (BMI1), an epigenetic regulator, is crucial in preserving mitochondrial homeostasis. We showed the administration of Ab-ECSnps inhibits calpain's translocation into mitochondria while promoting the translocation of BMI1 to mitochondria, thereby conferring neurotherapeutic benefits by enhancing cell viability, increasing mitochondrial DNA copy number, and preserving mitochondrial membrane potential. Further, we showed a novel molecular mechanism of BMI1 regulation by calpain that might contribute to maintaining mitochondrial homeostasis for attenuating PD. Concomitantly, Ab-ECSnps showed neurotherapeutic potential in the in vivo PD model. We showed for the first time that our brain-specific targeted delivery might regulate calpain-mediated BMI1 expression, thereby preserving mitochondrial homeostasis to alleviate PD.

Green synthesis of chitosan nanoparticles using Cassia fistula leaf extract: evaluation of antimicrobial, antioxidant, antibiofilm, and cytotoxic activities.

The emerging field of green synthesis within nanobiotechnology presents significant environmental and economic advantages compared to conventional methodologies. This study investigates the synthesis and application of chitosan nanoparticles (ChNPs) using Cassia fistula (CF) leaf extract as a sustainable, and bio-based approach. Characterization of CF-ChNPs confirmed effective bioconversion and also demonstrated significant antimicrobial activity. Notably, CF-ChNPs demonstrated a remarkable antimicrobial effect against Pseudomonas aeruginosa, with a zone of inhibition of 17 ± 0.2 mm surpassing the impact on other organisms tested. The CF-ChNPs exhibited an initial burst release of 28 ± 0.28% after 2 h, gradually achieving a controlled release of 76.3 ± 0.43% within 24 h. In addition, CF-ChNPs exhibited an antioxidant activity of 43.1 ± 0.48% and showed excellent antibiofilm activity against Staphylococcus aureus in comparison to other organisms. The cell viability assay results have confirmed that CF-ChNPs do not have any negative impact on the viability of L929 fibroblasts, further highlighting their potential as versatile nanomaterials for treating microbial infections and other therapeutic applications.

CpG Oligodeoxynucleotide-Coated Chitosan Nanoparticles Enhance Macrophage Proinflammatory Phenotype In Vitro.

This study aimed to investigate the effects of CpG Oligodeoxynucleotide (CpG ODNs)-Coated Chitosan Nanoparticles (CNP) on the phenotype of murine macrophages and their pro-inflammatory cytokine profile in vitro. CNP-CpG ODNs loaded with FITC-scrambled siRNA were prepared using the ionotropic gelation method. Peritoneal macrophages were isolated and exposed to CNP-CpG ODNs. Treated macrophages were assessed for uptake capacity. Flow cytometry was used to evaluate the expression levels of MHC-II, CD40, and CD86 costimulatory molecules in treated macrophages. Furthermore, the secretion levels of proinflammatory cytokines (TNF-α and IL-6) and the release of nitric oxide (NO) were measured in the culture supernatant of treated macrophages using sandwich ELISA and the Griess reaction, respectively. These in vitro studies showed that CNP-CpG ODNs had no cytotoxic effect on macrophages and were efficiently taken up by them. Additionally, CNP-CpG ODNs significantly increased the production of TNF-α, IL-6, and NO in the culture supernatant compared to CNP alone. Moreover, CNP-CpG ODNs enhanced the expression of MHC-II, CD40, and CD86 costimulatory molecules on macrophages. These findings indicate that incorporating CpG ODNs into CNPs promotes macrophage maturation and a proinflammatory phenotype. Therefore, CNP-CpG ODNs may serve as an effective system for targeted gene delivery to macrophages, enhancing immune responses.

The protective effects of chitosan and curcumin nanoparticles against the hydroxyapatite nanoparticles-induced neurotoxicity in rats.

Hydroxyapatite nanoparticles (HANPs) have extensive applications in biomedicine and tissue engineering. However, little information is known about their toxicity. Here, we aim to investigate the possible neurotoxicity of HANPs and the possible protective role of chitosan nanoparticles (CNPs) and curcumin nanoparticles (CUNPs) against this toxicity. In our study, HANPs significantly reduced the levels of neurotransmitters, including acetylcholine (Ach), dopamine (DA), serotonin (SER), epinephrine (EPI), and norepinephrine (NOR). HANPs significantly suppressed cortical expression of the genes controlling mitochondrial biogenesis such as peroxisome proliferator activator receptor gamma coactivator 1α (PGC-1α) and mitochondrial transcription factor A (mTFA). Our findings revealed significant neuroinflammation associated with elevated apoptosis, lipid peroxidation, oxidative DNA damage and nitric oxide levels with significant decline in the antioxidant enzymes activities and glutathione (GSH) levels in HANPs-exposed rats. Meanwhile, co-supplementation of HANP-rats with CNPs and/or CUNPs significantly showed improvement in levels of neurotransmitters, mitochondrial biogenesis, oxidative stress, DNA damage, and neuroinflammation. The co-supplementation with both CNPs and CUNPs was more effective to ameliorate HANPs-induced neurotoxicity than each one alone. So, CNPs and CUNPs could be promising protective agents for prevention of HANPs-induced neurotoxicity.