Loaded Chitosan Nanoparticles Research Articles

Synergistic and antibiofilm activity of DNase I and glucose oxidase loaded chitosan nanoparticles against dual-species biofilms of Listeria monocytogenes and Salmonella

Salmonella and Listeria monocytogenes are two of the most common foodborne pathogens in the food industry. They form dual-species biofilms, which have a higher sensitivity to antimicrobial treatment and a greater microbial adhesion. In this experiment, we loaded DNase I and glucose oxidase (GOX) on chitosan nanoparticles (CSNPs) to explore their inhibitory effects on and disruption of dual-species biofilms of Salmonella enterica and L. monocytogenes. Transmission electron microscopy (TEM) showed that CSNP-DNase-GOX and CSNPs were spherical in shape. CSNP-DNase-GOX was shifted and altered compared to the infrared peaks of CSNPs. CSNPs loaded with DNase I and GOX showed an increase in the particle size and an alteration in the polydispersity index (PDI) and the zeta potential. Compared to free DNase I or GOX, DNase I and GOX loaded on CSNPs had higher stability at different temperatures. CSNP-DNase-GOX was more effective in inhibiting dual-species biofilms than CSNP-GOX. Scanning electron microscopy (SEM) and fluorescence microscopy were used to observe the structure of the biofilm, which further illustrated that CSNP-DNase-GOX disrupted the dual-species biofilms of S. enterica and L. monocytogenes.

In vitro cytotoxic and genotoxic effects of Phyllanthus niruri extract loaded chitosan nanoparticles in TM4 cells and their influence on spermatogenesis

Purpose: This paper introduces a complete in vitro investigation of cytotoxic and genotoxic effects of Phyllanthus niruri extract loaded chitosan nanoparticles (PNNP) on mouse Sertoli cell line (TM4), as well as their impact on spermatogenesis. Methods: Chitosan nanoparticles (ChNP) and PNNP were prepared using an ionic gelation process, while their cytotoxicity on TM4 cells was assessed using the Cell Counting Kit-8 (CCK-8) assay. Comet and fast halo assays were used to quantify single-strand DNA breaks in TM4 cells. To detect changes in cell morphology during apoptosis, nuclear staining with Hoechst 33342 was performed. An immunofluorescence assay was employed to examine the expression level of proteins connexin 43 and Claudin 11 in TM4 cells after exposure to PNNP concentration of 125 µg/mL. Results: The synthesized PNNP had a size of 170.6 nm, a polydispersity index of 0.269, a zeta potential of +37.8 mV, and a good entrapment efficiency of 71.0%. Encapsulation of Phyllanthus niruri into ChNP induced DNA damage in TM4 cells as determined by alkaline comet and fast halo assay (FHA). Additionally, it stimulated apoptosis, as determined by changes in cell morphology by Hoechst 33342 staining. There was significant down regulation of blood-testis barrier (BTB) proteins in TM4 cells after exposure to PNNP which could compromise the integrity of BTB and subsequently disrupt spermatogenesis process in male. Conclusion: Our investigation confirms the cytotoxic and genotoxic effects of PNNP in TM4 cells, which could lead to spermatogenesis disruption and male infertility.

Synthesis, Characterization and Drug Release Study of Novel Guided Tissue Regeneration Membranes Containing Drug Loaded Chitosan Nanoparticles

Periodontitis is an inflammatory disease which can cause the destruction of the supporting tissues of the tooth leading to tooth loss. The guided tissue regeneration is considered as a gold standard for its treatment but the re-infection of surgical site limits its overall success. Objective: To synthesize novel monolayer guided tissue regeneration (GTR) membrane containing drug loaded chitosan nanoparticles and to evaluate the drug release from the synthesized GTR membranes. Methods: The chitosan nanoparticles containing ciprofloxacin were synthesized by the ionotropic gelation method and these synthesized nanoparticles were added into chitosan GTR membrane fabricated by the freeze gelation method. For comparison GTR membrane was prepared as a control by freeze gelation method in which the drug was added directly. The prepared membranes were characterized by the SEM and FTIR. The drug release was measured from the membrane samples in the phosphate buffer saline (PBS) at 1, 3, 5, 7 and 9 days. Results: The GTR membrane containing the ciprofloxacin loaded chitosan nanoparticles showed fast drug release as compared to the membrane in which the ciprofloxacin was added directly. Conclusions: The inclusion of antibiotic loaded chitosan nanoparticles can increase the drug release from GTR membrane.

Nephroprotective effects of silymarin and its fabricated nanoparticles against aluminum-induced oxidative stress, hyperlipidemia, and genotoxicity.

Aluminum (Al) is a ubiquitous element with proven nephrotoxicity. Silymarin (SM) is a mixture of polyphenolic components extracted from Silybum marianum and exhibited protective influences. However, SM bioactivity can be enhanced by its incorporation in chitosan (CS) through the use of nanotechnology. This work proposed to assess the protective influence of SM and its loaded chitosan nanoparticles (SM-CS-NPs) on aluminum chloride (AlCl3)-induced nephrotoxicity. Six groups were created randomly from 42 male Wistar rats and each one contains 7 rats (n = 7). Group I, acted as a control and received water. Group II received SM (15 mg/kg/day) and group III administered with SM-CS-NPs (15 mg/kg/day). Group IV received AlCl3 (34 mg/kg) and groups V and VI were treated with SM and SM-CS-NPs with AlCl3 respectively for 30 days. AlCl3 administration significantly elevated TBARS, H2O2, and kidney function levels besides LDH activity. Whereas GSH, CAT, SOD, GPx, GST, and GR values were all substantially reduced along with protein content, and ALP activity. Additionally, significant alterations in lipid profile, hematological parameters, and renal architecture were observed. Moreover, TNF-α, TGF-β, and MMP9 gene expression were upregulated in kidney tissues. The administration of SM or its nanoparticles followed by AlCl3 intoxication attenuated renal dysfunction replenished the antioxidant system, and downregulated TNF-α, TGF-β, and MMP9 gene expression in renal tissues compared to the AlCl3 group. SM-CS-NPs have more pronounced appreciated protective effects than SM and have the proficiency to balance oxidant/antioxidant systems in addition to their anti-inflammatory effect against AlCl3 toxicity.

Development and characterization of plant derived wastes Nano-formulation loaded in thermo-reversible gel for burn healing: An effort towards Sustainable Development

The duty of research is to suggest solutions to ailments affecting humans. Recently, there has been a demand that these solutions should be environmentally responsible, eco-friendly and coincide with sustainable development goals. From this perspective, the objective of this study was to develop thermo-reversible and healing promoting gel formulations. The gel base incorporated Natural Plant derived Wastes’ ethanolic extracts of either Kiwi peels (KE) or Yucca seeds (YE) (antioxidant, vitamins and anti-inflammatory natural agent) loaded chitosan nanoparticles for enhancement of burn healing performance. Comparative evaluation was done to all formulations to find the best competitor to conventional marketed drug formulations. Both extracts were standardized using HPLC. The lipoid content of YE was investigated using GC-MS, showing a content of 32.78 and 15.7 %of linoleic and pamiticmethyl esters, respectively. The nanoparticles characterization and the in-vitro physicochemical characteristics of the final dosage form formulations were assessed, revealing86.65 and 76.6 % entrapment efficiency, 311.4 and 198.1 nm particle size for KE and YE nanoformulations, respectively. The efficacy of the formulations was investigated in vivo against the commercial burn healing drug Mebo®, biochemical parameters and histopathology were statistically investigated. Reduction in wound area reached 69.12 and 72.01 % on day 12 for KE and YE nanoformulations, respectively. The YE encapsulated within chitosan nanoparticles loaded gel showed a promising and a significant healing effect comparable to the most commonly used marketed drug product (Mebo®) and possible mechanisms involved in the phases of healing were illustrated. Eco-friendly waste herbal extracts-loaded chitosan nanoparticles in thermo-reversible gel have been successfully developed from the two extracts: Kiwi peels and yucca seeds for burn and wound healing. This confirms the possible use of traditional medicines in advanced formulations to satisfy the future market of pharmaceuticals.

Effects of Exercise Training and L-Arginine Loaded Chitosan Nanoparticles on Hippocampus Histopathology, β-Secretase Enzyme Function, APP, Tau, Iba1and APOE-4 mRNA in Aging Rats.

The objective of this study was to evaluate the combined and independent effects of exercise training and L-Arginine loaded chitosan nanoparticles (LA CNPs) supplementation on hippocampal Tau, App, Iba1, and ApoE gene expression, oxidative stress, β-secretase enzyme activity, and hippocampus histopathology in aging rats. Thirty-five male Wistar rats were randomly assigned to five groups (n = 7 in each): Young (8 weeks old), Old (20 months old), old + L-arginine supplementation (Old Sup), old + exercise (Old Exe) and old + L-arginine supplementation + exercise (Old Sup + Exe). LA CNPs were administered to the supplement groups through gavage at a dosage of 500mg/kg/day for 6-weeks. Exercise groups were subjected to a swimming exercise program five days/week for the same duration. Upon the completion of their interventions, the animals underwent behavioral and open-field task tests and were subsequently sacrificed for hippocampus genetic and histopathological evaluation. For histopathological analysis of brain, Cresyl violet staining was used. Congo Red staining was employed to confirm amyloid plaques in the hippocampus. Expressions of Tau, App, Iba1, and ApoE genes were determined by real-time PCR. In contrast to the Old group, Old Exe and Old Sup + Exe groups spent more time in the central space in the open field task (p < 0.05) and have more live cells in the hippocampus. Old rats (Old, Old Sup and Old Exe groups) exhibited a significant Aβ peptide accumulation and increases in APP, Tau, Iba1, APOE-4 mRNA and MDA, along with decreases in SOD compared to the young group (p < 0.05). However, LA CNPs supplementation, exercise, and their combination (Old Sup, Old Exe and Old Sup + Exe) significantly reduced MDA, Aβ plaque as well as APP, Tau, Iba1, and APOE-4 mRNA compared to the Old group (p < 0.05). Consequently, the administration of LA CNPs supplements and exercise might regulate the risk factors of hippocampus cell and tissue.

Synthesis and evaluation of berberine loaded chitosan nanocarrier for enhanced in-vitro antioxidant and anti-inflammatory potential

Berberine, a naturally occurring isoquinoline plant alkaloid molecule, finds application in traditional medicine due to its extensive pharmacological effects but it cannot be clinically exploited to its fullest as it possesses poor water solubility and bioavailability. In order to address this issue, we have synthesized berberine loaded chitosan nanoparticles (BCNPs) using DMSO as surfactant and chitosan as polymer using modified ionic complexation approach and optimized the process utilizing central composite design. The BCNPs were empirically assessed for various parameters such as particle size distribution, zeta potential, drug encapsulation efficiency and surface morphology using established methodologies. BCNPs were additionally assessed for in-vitro antibacterial activity, in-vitro antioxidant activity, in-vitro anti-inflammatory activity, and sustained drug release behavior using established techniques. Experimental results showed that chitosan at a concentration of 0.05 % (w/v) and DMSO at a concentration of 1 % (v/v) successfully generated nanoparticles with a spherical shape with size ranging from 20 to 60 nm and exhibited a stabilizing zeta potential of 26.1 mV. Additionally, they had a high encapsulation effectiveness of 94.01 %. Sustained release was observed with 74.30 % berberine released in 48 h, respectively from BCNPs. The antimicrobial assays reveal that BCNPs exhibit superior antibacterial effectiveness against all bacterial strains compared to berberine alone as determined by the agar well diffusion method. The BCNPs also exhibited a substantial enhancement in DPPH activity and a greater percentage of protection compared to berberine. In summary, our research suggests that chitosan nanocarrier can enhance the solubility of berberine and facilitate the development of novel naturally-derived antioxidants and anti-inflammatory compounds. This study will further provide an insight into the future development of natural drug discovery.

Genotoxicity and Anti-Cancer Activity of Tamoxifen and Ivermectin Loaded Chitosan Nanoparticles Against MCF-7 Cell Line

Genotoxicity and Anti-Cancer Activity of Tamoxifen and Ivermectin Loaded Chitosan Nanoparticles Against MCF-7 Cell Line

Effect of C7-3-Peptide-Loaded Chitosan Nanoparticles Against Multi-Drug-Resistant Neisseria gonorrhoeae.

The emergence of Neisseria gonorrhoeae-resistant strains represents one of the most urgent global threats. In this regard, C7-3 peptide is one of the anti-virulence therapies that has demonstrated promising anti-gonococcal activity. Accordingly, this research aimed to formulate C7-3 peptide and its derivatives in chitosan nanoparticles. The peptide loaded chitosan nanoparticles were prepared using ion gelation method, and their physicochemical characteristics were investigated. The anti-gonococcal and antibiofilm activity of prepared NPs was assessed, and their cytotoxicity in human ovarian cells was evaluated. All prepared NPs were optimized for the smallest particle size of 136.9 to 168.3 nm. The EE% of C7-3, C7-3m1, and C7-3m2 CNPs reached 90.2, 92.5, and 91.8%, respectively. An in vitro release study demonstrated a continuous sustained-release pattern of C7-3 peptide from NPs. The SDS-PAGE assay confirmed the integrity of C7-3 peptide after the fabrication process. When comparing each peptide alone, the generated NPs demonstrated higher anti-gonococcal and anti-biofilm effectiveness against standard and resistant bacterial strains under anaerobic conditions. The cytotoxicity experiments revealed the cytocompatibility of NPs in HeLa cell lines. Given the advantages of enhanced anti-gonococcal activity of the C7-3 peptide and its derivatives when loaded with CNPs, as well as the antimicrobial properties of chitosan NPs, the reported NPs have great potential in the treatment of gonococcal infection.

In vitro and functional investigation reveals the curative effect of thymoquinone from black cumin-loaded chitosan nanoparticles on streptozotocin induced paediatric diabetes

Diabetic ketoacidosis (DKA) is regarded to be a communal complication of both type 1 and type 2 diabetes mellitus in children and adolescents. Successful therapy of DKA in children requires prompt diagnosis, strict monitoring of medical indicators, and prompt action. Thymoquinone (Tq) from black cumin loaded chitosan nanoparticles (ChNPs) intend to assess an effective agent to overcome this problem. XRD, FTIR, SEM, and TEM were used in the physicochemical analysis. Enzymatic activity of α-amylase and α-glucosidase was used in in vitro tests of anti-diabetic efficacy. Protecting insulin against enzyme breakdown is a crucial part of the insulin delivery mechanism. In the STZ-induced diabetes RIN-5F cell line, the anti-apoptotic capability of Tq-ChNPs was demonstrated through the NF-κB mediated apoptotic pathway. The combination of thymoquinone and chitosan NPs demonstrated that a wide variety of incredibly effective substances to elevate their curative effects, thus contributing to the growth of clinical and pharmaceutical fields.

Synthesis, characterization and insecticidal activity of Mentha spicata essential oil loaded polymeric nanoparticles

Chemical insecticides are often employed to manage stored grain pests. However, their use could have severe consequences for consumers and the environment. Thus, nanotechnology could present intriguing answers to issues related to agricultural and the food sectors. In the present investigation, Mentha spicata essential oil (MsEO) loaded chitosan nanoparticles (MsEO/CSNPs) were synthesized and characterized using FTIR, SEM, TEM, DLS and XRD. It was observed that the average size of the nanoparticles ranged between 50 and 200 nm with 0.428 and 0.222 PDI for the MsEO loaded chitosan nanoparticles (MsEO/CSNPs1) and MsEO loaded chitosan nanoparticles (MsEO/CSNPs2), respectively. SEM and TEM studies revealed spherical nature of the nanoparticles. Loading Capacity (LC) was found to be 6.62–4.19% and encapsulation efficiency (EE) ranged from 79.5 to 82.5% in MsEO/CSNPs1 and MsEO/CSNPs2. Further, MsEO-loaded chitosan nanoparticles (MsEO/CSNPs1 and MsEO/CSNPs2) demonstrated excellent antioxidant activity with IC50 values of 24.2 μg/mL and 30.9 μg/mL, suggesting that MsEO/CSNPs might be employed for an effective natural antioxidant agent. The synthesized MsEO/CSNPs showed strong insecticidal efficacy when used for Callosobruchus maculates (LC50 56 μL/L) and Sitophilus granaries (LC50 47 μL/L) in toxicity tests. These nanoparticles were also tested for cytotoxicity on the Vero cell line, and the results revealed that they were nontoxic. The findings demonstrate that Mentha spicata essential oil (MsEO) loaded chitosan nanoparticles (MsEO/CSNPs) is an innovative development that might be used in a food storage pest control strategy for Callosobruchus maculatus and Sitophilus granaries.

Preparation and characterization of 3D bioprinted gelatin methacrylate hydrogel incorporated with curcumin loaded chitosan nanoparticles for in vivo wound healing application

This study developed a biomimetic composite bioink consisting of gelatin methacrylate (GelMA) /chitosan nanoparticles (CSNPs) for extrusion-based 3D bioprinting. Additionally, curcumin(Cur)-loaded nanoparticles were incorporated which increased the proliferation and antibacterial activity of biomimetic skin constructs. The hydrogel, curcumin-loaded NPs, and the biocomposite was characterized chemically and physically. The results indicated proper modified gelatin with tunable physical characteristics, e.g., swelling ratio and biodegradability up to 1200 % and 25 days, respectively. In addition, the characterized CSNPs showed good distribution with a size of 370 nm and a zeta potential of 41.1 mV. We investigated the mechanical and cytocompatibility properties of chitosan nanoparticles encapsulated in hydrogel for emulating an extracellular matrix suitable for skin tissue engineering. CSNPs entrapped in GelMA (15 % w/v) exhibited controlled drug release during 5 days, which was fitted into various kinetic models to study the mass transfer mechanism behavior. Also, the composite hydrogels were effective as a barrier against both gram-positive and gram-negative bacteria at a concentration of 50 μg/ml nanoparticles in GelMA 15 %. Furthermore, the biocomposite was applied on Wistar rats for wound healing. As a result, this study provides a GelMA-NP50-Cur3 scaffold that promotes cell proliferation and decreases microbial infections in wounds.

Metronidazole loaded chitosan–phytic acid polyelectrolyte complex nanoparticles as mucoadhesive vaginal delivery system for bacterial vaginosis

Bacterial vaginosis (BV) is a recurring infection that is difficult to treat due to the limited bioavailability of antimicrobials. In this study, Metronidazole (MTZ)-loaded chitosan nanoparticles (MCSNP) were synthesized employing phytic acid (PA) as a crosslinking agent for treating bacterial vaginosis. The prepared MCSNPs were characterized for size, shape, surface charge, compatibility, cytotoxicity, biofilm inhibition, and in-vitro/in-vivo antimicrobial activities. Morphological examination revealed that nanoparticles generated from 0.535 % w/v chitosan and 0.112 % w/v PA were non-spherical, discontinuous, and irregular, with zeta potential ranging from 25.00 ± 0.45 to 39 ± 0.7. The results of DSC and XRD demonstrated no change in the physical state of the drug in the finished formulation. The optimized formulation demonstrates a cumulative drug release of about 98 ± 1.5 % within 8 h. Antimicrobial studies demonstrated that the optimized formulation had enhanced efficacy against acid-adapted BV pathogens, with a MIC value of 0.9 ± 0.1 μg/mL. Compared to the MTZ alone, the in-vivo antibacterial results of in the case of developed nanoparticles showed a four-fold reduction in bacterial count in female Swiss albino mice. Based on the experimental findings, it was concluded that MCSNPs, due to their excellent physiochemical and antibacterial properties, could serve as a potential topical alternative for treating BV.

Preparation and Evaluation of Chitosan Nanoparticles containing Iranian Eschium Amoenum Extract and its Antimicrobial Effects on Common Oral Microorganisms

Background and Aim: Chitosan nanoparticles are one of the biocompatible and bioactive vectors in medicine contributing to the transfer and slow release of antimicrobial agents. The present study investigated loading Echium amoenum extract on chitosan nanoparticles and evaluated the antimicrobial effects of this composite on Streptococcus mutans, Candida albicans, and Escherichia coli. Materials and Methods: First, a chitosan solution was prepared in 1% acetic acid. Then, a tripolyphosphate (TPP) solution was added to it. The resulting mixture was centrifuged, and finally, its powder was dried. The E. amoenum extract was prepared and added to the chitosan powder. After mixing, the mixture was centrifuged, and the chitosan nanoparticle powder containing E. amoenum was separated and dried. The properties and characteristics of the nanoparticles were determined by the DLS test, and their stability was evaluated using the zeta potential. Finally, the antimicrobial effect of this product was evaluated on S. mutans, E. coli, and C. albicans using MIC and MBC through the microdilution method. Results: The sizes of chitosan nanoparticles and chitosan nanoparticles containing the plant extract were 98±1.24 and 108±1.54 nm and their zeta potentials were +17 and +10, respectively. The MIC for chitosan, the extract, and chitosan nanoparticles containing E. amoenum extract for E. coli were 170.67, 666.67, and 341.34 mg/mL; these values for S. mutans were 106.67, 416.67, and 170.67 mg/mL, with 426.67, 1000, and 341.34 mg/mL for C. albicans, respectively. The MBC for chitosan, the extract, and chitosan nanoparticles containing E. amoenum extract for E. coli were 426.67, 1666.67, and 853.34 mg/mL; these values for S. mutans were 426.67, 833.34, and 426.67 mg/mL, with 853.34, 1666.67, and 853.34 mg/mL for C. albicans, respectively. Conclusion: Chitosan nanoparticles are an efficient vector for E. amoenum extract and loaded chitosan nanoparticles can be used as a bioactive antibacterial agent against various oral microorganisms.

Vitis Pedata Nanoformulation in the Management of Alloxan Induced Experimental Diabetes

Vitis pedata is a woody climber of the Vitaceae family with a multitude of pharmacological effects like anti-inflammatory, antibacterial, anti-nociceptive, anti-arthritic, anti-oxidant, astringent, and hemostatic qualities. The research targets to assess the anti-diabetic efficacy of Vitis pedata aqueous extract nanoformulation in alloxan-induced diabetes rats. Biocompatible polycationic polymer chitosan is used for nanoformulation development. The aqueous extract loaded chitosan nanoparticle formulation displayed a particle size of 186± 5.37 nm with a polydispersity index of 0.226 and zeta potential value of 23 ± 1.93 mV. The nanoformulations were assessed for its anti-diabetic properties in comparison to aqueous extracts for the first time by in- vivo methodologies. Several parameters like body weight, blood glucose level, blood and serum biomarkers, were examined. Changes in tissue histoarchitecture, liver glycogen content, oxidative stress response and antioxidant status were also studied. In diabetic rats, the nano-scale formulation significantly reduced blood glucose levels, glucose tolerance, lipid profiles, and serum biomarkers, comparable to the oral hypoglycemic medication glibenclamide. The restoration of antioxidant status and pancreatic histoarchitecture through by size assisted delivery may be related to the improved control of diabetes by the nanoformulation than the extract alone. The work marks the first report of Vitis pedata nanoformulation for diabetes management and can serve as a prelude for further preclinical/clinical evaluations.

Quercetin and 5-Fu Loaded Chitosan Nanoparticles Trigger Cell-Cycle Arrest and Induce Apoptosis in HCT116 Cells via Modulation of the p53/p21 Axis.

Nanoparticles (NPs) are encapsulating agents that exist in the nanometer range. They can be classified into different classes based on their properties, shapes, or sizes. Metal NPs, fullerenes, polymeric NPs, ceramic NPs, and luminescent nanoporous hybrid materials are only a few examples. This study explored the anticancer potential of quercetin and 5-fluorouracil-encapsulated chitosan nanoparticles (CS-5-FU-QCT NPs). The nanoparticles were prepared by ionic gelation, and their efficacy and mechanism of action were examined. CS-5-FU-QCT NPs were characterized using dynamic light scattering (DLS), atomic force microscopy (AFM), UV-visible spectroscopy, and Fourier transform infrared spectroscopy (FTIR); cytotoxicity was analyzed using an MTT assay. Cells were treated with CS-5-FU-QCT NPs and incubated for 12, 24, and 36 h, and apoptosis analysis (using Annexin V/FITC), cell-cycle analysis, Western blotting, and confocal microscopic analysis were performed. Biophysical analysis revealed that the CS-5-FU-QCT NPs fall in the range of 300-400 nm with a near-spherical shape. The in vitro drug release profile indicates sustained release of drugs over a period of about 36 h. The cytotoxicity of CS-5-FU-QCT NPs was more prominent in HCT116 cells than in other cancer cells. This particular nanoformulation caused G0/G1 phase cell-cycle arrest in HCT116 cells and induced intracellular ROS generation, thereby causing apoptosis. It also downregulated Bcl2, cyclin D1, and Cdk4 and upregulated BAX, p53, and p21, causing cell-cycle arrest and apoptosis. In summary, CS-5-FU-QCT NPs hindered proliferation of HCT116 cells via ROS generation and altered the expression of key proteins in the p53/p21 axis and apoptotic machinery in a time-dependent manner.

Hyaluronic acid engineered gallic acid embedded chitosan nanoparticle as an effective delivery system for treatment of psoriasis

Psoriasis is a deleterious auto-immune disorder which seriously harms the patients physical and mental health. CD44 are found to be over-expressed on psoriatic lesions which are highly responsible for epidermal hyperproliferation and inflammation. Gallic acid (GA), a phenolic acid natural compound has potential inhibitory impact on pro-inflammatory transcription factors. However, the penetration across skin and availability is low when applied topically, making the treatment extremely challenging. Considering such factors, we developed GA loaded chitosan nanoparticles and modified with hyaluronic acid (HA) (HA@CS-GA NP) to assess the therapeutic potential against psoriasis. The formulations were characterized by DSC, zetasizer and TEM for assuring the development of nanosystems. GA loaded CS NP had a particle size of 207.2 ± 0.08 nm while after coating with HA, the size increased to 220.1 ± 0.18 nm. The entrapment efficiency was 93.24 ± 0.132% and drug loading of 73.17 ± 0.23%. The in vitro cell viability assessment study confirmed enhanced anti-proliferative effect of HA@CS-GA NP over plain GA which is due to high sensitivity towards HaCaT cell. The in vivo results on imiquimod induced psoriasis model indicated that CD44 receptor mediated targeted approach of HA@CS-GA NP gel had great potential in restricting the keratinocyte hyperproliferation and circumventing psoriasis. For the therapy of further skin-related conditions, HA modified nanoparticles should be investigated extensively employing genes, antibodies, chemotherapeutics, or natural substances.

Nose to brain delivery of Astragaloside IV by β-Asarone modified chitosan nanoparticles for multiple sclerosis therapy

Multiple sclerosis (MS), an autoimmune disease, has been considered an inflammatory disorder of the central nervous system (CNS) with demyelination and axonal damage. Although there are certain first-line therapies to treat MS, their unsatisfactory efficacy is partly due to the limited CNS access after systemic administration. Besides, there is an urgent need to treat MS by enhancing remyelination or neuroprotection, or dampen the activity of microglia. Astragaloside IV (ASI) bears anti-inflammatory, antioxidant, remyelination and neuroprotective activity. While its poor permeability, relatively high molecular weight and low lipophilicity restrict it to reach the brain. Therefore, β-asarone modified ASI loaded chitosan nanoparticles (ASI-βCS-NP) were prepared to enhance the nose-to-brain delivery and therapeutic effects of ASI on EAE mice. The prepared ASI-βCS-NP showed mean size of about 120 nm, and zeta potential from +19 to +25 mV. DiR-βCS-NP was confirmed with good nose-to-brain targeting ability. After intranasal administration, the ASI-βCS-NP significantly reduced behavioral scores, decreased weight loss, suppressed inflammatory infiltration and astrocyte/microglial activation, reduced demyelination and increased remyelination on a mice EAE model. Our findings indicate that ASI-βCS-NP may be a potent treatment for MS after nose-to-brain drug delivery.

Synthesis and Standardization of Sodium Nitroprusside Nanoformulation on Germination and Early Seedling Growth of Maize under PEG- Induced Moisture Stress

Background: Sodium nitroprusside (SNP) is a common substance used to decrease the harmful effects of abiotic stress and to improve the germination and early seedling growth of crops. However SNP use is limited by its short lifespan and photosensitivity. With this context, current study taken up to that synthesize of SNP loaded chitosan nanoparticles and to standardize for the seed treatment. Methods: SNP loaded chitosan nanoparticles were successfully synthesized by using ionic gelation method. A variety of characterization techniques utilized viz., Dynamic Light Scattering (DLS), Fourier-Transform Infrared Spectroscopy (FT-IR) and release kinetics. A laboratory experiment was conducted to standardize the ideal SNP nanoformulation dosage for seed treatment in order to minimize the negative impacts of drought stress in maize. The treatments involved soaking seeds in solutions containing various concentrations of SNP nanoformulation, including 20, 40, 60, 80 and 100 ìM including control. Result: The experimental results indicated that, among SNP nanoformulation concentrations, seeds treated with @ 100 ìM concentration showed the highest germination percentage (85%), promptness index (82.3%), vigor index (1624%), shoot and root length (8.4 cm and 11 cm), fresh and dry weight of shoot (123.7 and 61.6 mg/20seedlings) and root (52.6 and 25.0 mg/20seedlings) respectively, under PEG-induced drought stress conditions compared with control.

Synergistic antibacterial activity of carvacrol loaded chitosan nanoparticles with Topoisomerase inhibitors and genotoxicity evaluation

The increasing prevalence of antibiotic resistant bacteria is a significant healthcare crisis with substantial socioeconomic impact on global community. The development of new antibiotics is both costly and time-consuming prompting the exploration of alternative solutions such as nanotechnology which represents opportunities for targeted drug delivery and reduced MIC. However, concerns have arisen regarding genotoxic effects of nanoparticles on human health necessitating an evaluation of nanoparticle induced DNA damage.This study aimed to investigate the antibacterial potential of already prepared, characterized chitosan nanoparticles loaded with carvacrol and their potential synergism with Topoisomerase II inhibitors against S. aureus, E. coli and S. typhi using agar well diffusion, microdilution and checkerboard method. Genotoxicity was assessed through comet assay.Results showed that both alone and drug combinations of varying concentrations exhibited greater zones of inhibition at higher concentrations. Carvacrol nanoparticles combined with ciprofloxacin and doxorubicin significantly reduced MIC compared to the drugs used alone. The MIC50 values for ciprofloxacin were 35.8 µg/ml, 48.74 µg/ml, 35.57 µg/ml while doxorubicin showed MIC50 values of 20.79 µg/ml, 34.35 µg/ml, 25.32 µg/ml against S. aureus, E. coli and S. typhi respectively. The FICI of ciprofloxacin and doxorubicin with carvacrol nanoparticles found ≤ 0.5 Such as 0.44, 0.44,0.48 for ciprofloxacin and 0.45, 0.45, 0.46 for doxorubicin against S. aureus, E. coli and S. typhi respectively revealed the synergistic effect. The analysis of comet assay output images showed alteration of DNA at high concentrations.Our results suggested that carvacrol nanoparticles in combination with Topoisomerase inhibitors may prevent and control the emergence of resistant bacteria with reduced dose.