Nano transdermal system combining mitochondria-targeting cerium oxide nanoparticles with all-trans retinoic acid for psoriasis

Psoriasis is an inflammatory skin disease that is intricately linked to oxidative stress.Antioxidation and inhibition of abnormal proliferation of keratinocytes are pivotal strategies for psoriasis.Delivering drugs with these effects to the site of skin lesions is a challenge that needs to be solved.Herein,we reported a nanotransdermal delivery system composed of all-trans retinoic acid(TRA),triphenylphosphine(TPP)-modified cerium oxide(CeO2)nanoparticles,flexible nanoliposomes and gels(TCeO_(2)-TRA-FNL-Gel).The results revealed that TCeO_(2)synthesized by the anti-micelle method,with a size of approximately 5 nm,possessed excellent mitochondrial targeting ability and valence conversion capability related to scavenging reactive oxygen species(ROS).TCeO_(2)-TRA-FNL prepared by the film dispersion method,with a size of approximately 70 nm,showed high drug encapsulation efficiency(>96%).TCeO_(2)-TRA-FNL-Gel further showed sustained drug release behaviors,great transdermal permeation ability,and greater skin retention than the free TRA.The results of in vitro EGF-induced and H2O2-induced models suggested that TCeO_(2)-TRA-FNL effectively reduced the level of inflammation and alleviated oxidative stress in HaCat cells.The results of in vivo imiquimod(IMQ)-induced model indicated that TCeO_(2)-TRA-FNL-Gel could greatly alleviate the psoriasis symptoms.In summary,the transdermal drug delivery system designed in this study has shown excellent therapeutic effects on psoriasis and is prospective for the safe and accurate therapy of psoriasis.

Cerium Oxide Nanoparticles Protect against Oxaliplatin Induced Testicular Damage: Biochemical, Histological, Immunohistochemical, and Genotoxic Study

Oxaliplatin is a chemotherapeutic drug used for colorectal cancer treatment. The testicular toxic effect is one of its recorded toxicities which resulted in a few studies. Oxidative stress could be a direct cause of this testicular toxicity. Cerium oxide nanoparticles (CONPs) are optimistic antioxidants for applications in medicine. The aim of the work is to study the protective effect of CONPs on testicular toxicity induced by oxaliplatin in rats. Forty adult male albino rats were divided into 4 groups: Control group, CONPs group (60 mg/kg, 5 times/week), Oxaliplatin group (4 mg/kg, twice/week), and Oxaliplatin & CONPs group, for 4 weeks. Seventy-two hours after the last administration, blood samples were taken for hormonal levels and testes were used for both histopathology and immunohistochemical microscopic examination. Sperm smears were also performed and their results were statistically analyzed to detect any sperm abnormalities. Oxaliplatin increased MDA levels. SOD and GPx activity was decreased. GSH levels were decreased. Also, it decreased the sperm cell count and serum testosterone, and anti-Müllerian hormon. In the testicular sections, significant histopathology changes were seen and immunohistochemical examination confirmed these results. Upon supplementation of CONPs with oxaliplatin decreased MDA levels. SOD and GPx activity was increased, and GSH did not change. In testicular sections, normal morphology was seen. Also, there was an increase in the sperm cell count and serum testosterone anti-Müllerian with significant improvement of testicular architecture, and immunohistochemical examination confirmed these results. The utilization of CONPs produced significant protection against all of the above-mentioned changes.

An overview on recent in vivo biological application of cerium oxide nanoparticles

Cerium oxide nanoparticles(CNPs)possess a great potential as therapeutic agents due to their ability to self-regenerate by reversibly switching between two valences+3 and+4.This article reviews recent articles dealing with in vivo studies of CNPs towards Alzheimer’s disease,obesity,liver inflammation,cancer,sepsis,amyotrophic lateral sclerosis,acute kidney injury,radiation-induced tissue damage,hepatic ischemia reperfusion injury,retinal diseases and constipation.In vivo anti-cancer studies revealed the effectiveness of CNPs to reduce tumor growth and angiogenesis in melanoma,ovarian,breast and retinoblastoma cancer cell-induced mice,with their conjugation with folic acid,doxorubicin,CPM,or CXC receptor-4 antagonist ligand eliciting higher efficiency.After conjugation with triphenylphosphonium or magnetite nanoparticles,CNPs were shown to combat Alzheimer’s disease by reducing amyloid-β,glial fibrillary acidic protein,inflammatory and oxidative stress markers in mice.By improving muscle function and longevity,the citrate/EDTA-stabilized CNPs could ameliorate amyotrophic lateral sclerosis.Also,they could effectively reduce obesity in mice by scavenging ROS and reducing adipogenesis,triglyceride synthesis,GAPDH enzyme activity,leptin and insulin levels.In CCl4-induced rats,stress signaling pathways due to inflammatory cytokines,liver enzymes,oxidative and endoplasmic reticulum messengers could be attenuated by CNPs.Commercial CNPs showed protective effects on rats with hepatic ischemia reperfusion and peritonitis-induced hepatic/cardiac injuries by decreasing oxidative stress and hepatic/cardiac inflammation.The same CNPs could improve kidney function by diminishing renal superoxide,hyperglycemia and tubular damage in peritonitis-induced acute kidney injury in rats.Radiation-induced lung and testicular tissue damage could be alleviated in mice,with the former showing improvement in pulmonary distress and bronchoconstriction and the latter exhibiting restoration in spermatogenesis rate and spermatid/spermatocyte number.Through enhancement of gastrointestinal motility,the CNPs could alleviate constipation in both young and old rats.They could also protect rat from light-induced retinal damage by slowing down neurodegenerative process and microglial activation.

Neuroprotective Potential of Cerium Oxide Nanoparticles for Focal Cerebral Ischemic Stroke

During the previous years, with the emerging of nanotechnology, the enormous capabilities of nanoparticles have drawn great attention from researchers in terms of their potentials in various aspects of pharmacology. Cerium oxide nanoparticles（nanoceria）, considered as one of the most widely used nanomaterials, due to its tempting catalytic antioxidant properties, show a promising potential in diverse disorders, such as cerebral ischemic stroke（CIS）, cancer, neurodegenerative and inflammatory diseases. Overwhelming generation of reactive oxygen species（ROS） and reactive nitrogen species（RNS） during cerebral ischemia and reperfusion periods is known to aggravate brain damage via sophisticated cellular and molecular mechanisms, and therefore exploration of the antioxidant capacities of nanoceria becomes a new approach in reducing cerebral ischemic injury. Furthermore, utilizing nanoceria as a drug carrier might display the propensity to overcome limitations or inefficacy of other conceivable neuroprotectants and exhibit synergistic effects. In this review, we emphasize on the principle features of nanoceria and current researches concerning nanoceria as a potential therapeutic agent or carrier in improving the prognosis of CIS.

A review on biomedical and dental applications of cerium oxide nanoparticles——Unearthing the potential of this rare earth metal

Nanotechnology deals with particles ranging from 1 to 100 nm in size called as nanoparticles.These nano particles exhibit unique properties which find an application in many industries and medical fields.A growing body of evidence points out the newer developing technologies adopted in the field of medicine in terms of target therapies,imaging systems,drug deliveries,etc.is through the incorporation of nanoparticles.Cerium oxide nanoparticles have gained attention in the last decade due to exceptional properties such as redox activity,biofilm inhibition,antibacterial activity,anti-inflammatory activity,etc.The method of synthesis of cerium oxide nanoparticles plays a pivotal role in its application.It exhibits redox properties and catalytic activity and thus has found its use in biomedical applications.Nanoparticles are incorporated into dental materials such as restorative cements/sealants,adhesives,and denture systems to improve their properties.Among the various metal oxide nanoparticles,ce rium oxide nanoparticles(CeO_(2)NPs)are known to exhibit lower toxicity to mammalian cells and possess unique antibacterial mechanism.In addition,they exhibit potent properties such as antitumor,antiinflammatory,antibacterial activities,and functions as an immunosensor.CeO_(2)NPs have excellent scavenging properties for reactive oxygen species,which is why they are being considered for therapeutic purposes.In this review,various methods of synthesis of CeO_(2)NPs are discussed.Several factors that determine the particle size and morphology of these materials are important for biomedical and dental applications.Emphasis is given to preparation methods and variables such as calcination temperature,which have a profound effect on particle size and morphology.This article also presents various applications of CeO_(2)NPs in the biomedical and dental fields.

In vitro and in vivo evaluation of cerium oxide nanoparticles in respiratory syncytial virus infection

Respiratory syncytial virus(RSV)is the most common cause of viral bronchiolitis among children worldwide,yet there is no vaccine for RSV disease.This study investigates the potential of cube and sphere-shaped cerium oxide nanoparticles(CNP)to modulate reactive oxygen(ROS)and nitrogen(RNS)species and immune cell phenotypes in the presence of RSV infection in vitro and in vivo.Cube and sphere-shaped CNP were synthesized by hydrothermal and ultrasonication methods,respectively.Physico-chemical characterization confirmed the shape of sphere and cube CNP and effect of various parameters on their particle size distribution and zeta potential.In vitro results revealed that sphere and cube CNP differentially modulated ROS and RNS levels in J774 macrophages.Specifically,cube CNP significantly reduced RSV-induced ROS levels without affecting RNS levels while sphere CNP increased RSV-induced RNS levels with minimal effect on ROS levels.Cube CNP drove an M1 phenotype in RSV-infected macrophages in vitro by increasing macrophage surface expression of CD80 and CD86 with a concomitant increase in TNFαand IL-12p70,while simultaneously decreasing M2 CD206 expression.Intranasal administration of sphere and cube-CNP were well-tolerated with no observed toxicity in BALB/c mice.Notably,cube CNP preferentially accumulated in murine alveolar macrophages and induced their activation,avoiding enhanced uptake and activation of other inflammatory cells such as neutrophils,which are associated with RSV-mediated inflammation.In conclusion,we report that sphere and cube CNP modulate macrophage polarization and innate cellular responses during RSV infection.

Synthesis,Structural and Optical Properties of Mn-Doped Ceria Nanoparticles:A Promising Catalytic Material

The structure,the morphology and the thermal,optical and the surface properties of nanocrystalline CeO_2 doped with Mn have been studied by X-ray diffraction（XRD）,field-emission transmission electron microscopy（FE-TEM）,energy-dispersive X-ray analysis,thermogravimetric analysis,UV–Vis absorption spectroscopy and Fourier transform infrared spectroscopy.The XRD results confirmed the successful incorporation of Mn into the CeO_2 lattice through the formation of nanoscale face-centered cubic solid solution.The FE-TEM observations supported the nanocrystalline nature of the solid solutions.The presence of structural defects and their role on the band gap have been discussed on the basis of absorption spectral studies.The structural differences correlate with results from temperature-programmed reaction（TPR）experiments with H_2 consumption.The TPR measurements showed an enhanced bulk reduction at much lower temperatures,indicating increased oxygen mobility in the samples,which enable to enhanced oxygen diffusion at lower temperatures.

Efficient removal of phosphate from aqueous solution using novel magnetic nanocomposites with Fe_3O_4@SiO_2 core and mesoporous CeO_2 shell

Fe_3O_4@SiO_2 magnetic nanoparticles functionalized with mesoporous cerium oxide（Fe_3O_4@SiO_2@mCeO_2） was fabricated as a novel adsorbent to remove phosphate from water. The prepared adsorbent was characterized by X-ray diffractometry（XRD）, transmission electron microscopy（TEM）, nitrogen adsorption-desorption and vibrating sample magnetometry（VSM）, and its phosphate removal performance was investigated through the batch adsorption studies. Characterization results confirmed that mesoporous cerium oxide was successfully assembled on the surface of Fe_3O_4@SiO_2 nanoparticles, and the synthesized adsorbent possessed a typical core-shell structure with a BET surface area of 195 m^2/g, accessible mesopores of 2.6 nm, and the saturation magnetization of 21.11 emu/g. The newly developed adsorbent had an excellent performance in adsorbing phosphate, and its maximum adsorption capacity calculated from the Langmuir model was 64.07 mg/g. The adsorption was fast, and the kinetic data could be best fitted with the pseudo-second-order kinetic model. The phosphate removal decreased with the increase of solution pH（2 to 10）, while the higher ionic strength slightly promoted the phosphate adsorption. The presence of Cl~– and SO^（2–）_4 could enhance the adsorption of phosphate whereas HCO~–_ 3 had interfering effect on the phosphate adsorption. The adsorption mechanism was studied by analyzing Zeta potential and FTIR spectroscopy, and the results indicated that the replacement of the surface hydroxyl groups by phosphate ions with the formation of inner-sphere complex played a key role in the phosphate adsorption. The spent adsorbent could be quickly separated from aqueous solution with the assistance of the external magnetic field, and the adsorbed phosphate could be effectively desorbed using a 1 mol/L NaOH solution.