Antineuroinflammatory Activities and Neurotoxicological Assessment of Curcumin Loaded Solid Lipid Nanoparticles on LPS-Stimulated BV-2 Microglia Cell Models

Curcumin, which is a potential antineuroinflammatory and neuroprotective compound, exhibits poor bioavailability in brain cells due to its difficulty in crossing the blood–brain barrier and its rapid metabolism during circulation, which decreases its efficacy in treating chronic neuroinflammatory diseases in the central nervous system. The bioavailability and potential of curcumin can be improved by using a nanodelivery system, which includes solid lipid nanoparticles. Curcumin-loaded solid lipid nanoparticles (SLCN) were efficiently developed to have a particle size of about 86 nm and do not exhibit any toxicity in the endothelial brain cells. Furthermore, the curcumin-loaded solid lipid nanoparticles (SLCN) were studied to assess their efficacy in BV-2 microglial cells against LPS-induced neuroinflammation. The SLCN showed a higher inhibition of nitric oxide (NO) production compared to conventional curcumin in a dose-dependent manner. Similarly, the mRNA and proinflammatory cytokine levels were also reduced in a dose-dependent manner when compared to those with free curcumin. Thus, SLCN could be a potential delivery system for curcumin to treat microglia-mediated neuroinflammation.

Download Full-text

Formulation and Development of Transferrin Targeted Solid Lipid Nanoparticles for Breast Cancer Therapy

Frontiers in Pharmacology ◽

10.3389/fphar.2020.614290 ◽

2020 ◽

Vol 11 ◽

Author(s):

Geeta S. Bhagwat ◽

Rajani B. Athawale ◽

Rajeev P. Gude ◽

Shadab Md ◽

Nabil A. Alhakamy ◽

...

Keyword(s):

Breast Cancer ◽

Solid Lipid Nanoparticles ◽

Human Breast Cancer ◽

Lipid Nanoparticles ◽

Dependent Manner ◽

Human Breast ◽

Solid Lipid ◽

Receptor Modulation ◽

Tamoxifen Citrate ◽

Mcf 7

Breast cancer is conventionally treated by surgery, chemotherapy and radiation therapy followed by post operational hormonal therapy. Tamoxifen citrate is a best option to treat breast cancer because its selective estrogen receptor modulation activity. Owing to its antiestrogenic action on breast as well as uterine cells, Tamoxifen citrate shows uterine toxicity. The dose 20 mg per day of Tamoxifen citrate required to show therapeutic effect causes side effects and toxicity to vital organs such as liver, kidney and uterus. In the present study, transferrin-conjugated solid lipid nanoparticles (SLNs) were successfully prepared to enhance the active targeting of tamoxifen citrate in breast cancer. Developed formulations were evaluated for particle size, surface charge, surface morphology and in vitro dissolution studies. Developed formulations exhibited more cytotoxicity as compared to pure Tamoxifen citrate solution in time as well as concentration dependent manner on human breast cancer MCF-7 cells. Further, cell uptake and flow cytometry studies confirmed the qualitative uptake of developed D-SLN and SMD-SLN by human breast cancer MCF-7 cells. Overall, proposed study highlights that transferrin engineered nanocarriers could enhance the therapeutic response of nanomedicines for breast cancer treatment.

Download Full-text

VitD3-loaded solid lipid nanoparticles: stability, cytotoxicity and cytokine levels

Journal of Microencapsulation ◽

10.1080/02652048.2017.1345995 ◽

2017 ◽

Vol 34 (5) ◽

pp. 454-462 ◽

Cited By ~ 6

Author(s):

Murat Demirbilek ◽

Nelisa Laçin Türkoglu ◽

Selçuk Aktürk ◽

Cem Akça

Keyword(s):

Solid Lipid Nanoparticles ◽

Lipid Nanoparticles ◽

Solid Lipid ◽

Cytokine Levels ◽

Nanoparticles Stability

Download Full-text

Development of Solid Lipid Nanoparticles by Cold Dilution of Microemulsions: Curcumin Loading, Preliminary In Vitro Studies, and Biodistribution

Nanomaterials ◽

10.3390/nano9020230 ◽

2019 ◽

Vol 9 (2) ◽

pp. 230 ◽

Cited By ~ 12

Author(s):

Daniela Chirio ◽

Elena Peira ◽

Chiara Dianzani ◽

Elisabetta Muntoni ◽

Casimiro Gigliotti ◽

...

Keyword(s):

Chemical Stability ◽

Solid Lipid Nanoparticles ◽

Lipid Nanoparticles ◽

Delivery Systems ◽

Dependent Manner ◽

Solid Lipid ◽

Cytotoxicity Studies ◽

Over Time

Background: Solid lipid nanoparticles (SLNs) are attractive drug delivery systems for lipophilic molecules like curcumin (CURC) with low chemical stability. Methods: A simple, innovative, and cold-operating method, named “cold dilution of microemulsion” is developed by the authors to produce SLNs. An oil-in-water microemulsion (µE), whose disperse phase consisted of a solution of trilaurin in a partially water-miscible solvent, was prepared after mutually saturating solvent and water. Trilaurin SLNs precipitated following solvent removal upon water dilution of the µE. After SLN characterization (mean size, Zeta potential, CURC entrapment efficiency, and over time stability), they were tested for in vitro cytotoxicity studies on pancreatic adenocarcinoma cell lines and for in vivo preliminary biodistribution studies in Wistar healthy rats. Results: CURC loaded SLNs (SLN-CURC) had mean diameters around 200 nm, were negatively charged, stable over time, and able to entrap CURC up to almost 90%, consequently improving its stability. SLN-CURC inhibited in vitro pancreatic carcinoma cell growth in concentration-dependent manner. Their in vivo intravenous administration suggested a possible long circulation. Conclusions: These results, according to a concomitant study on chitosan-coated SLNs, confirm the possibility to apply the developed SLN-based delivery systems as a means to entrap CURC, to improve both its water dispersibility and chemical stability, facilitating its application in therapy.

Download Full-text

A Role of Fluoride on Free Radical Generation and Oxidative Stress in BV-2 Microglia Cells

Mediators of Inflammation ◽

10.1155/2012/102954 ◽

2012 ◽

Vol 2012 ◽

pp. 1-8 ◽

Cited By ~ 25

Author(s):

Xi Shuhua ◽

Liu Ziyou ◽

Yan Ling ◽

Wang Fei ◽

Guifan Sun

Keyword(s):

Oxidative Stress ◽

Nitric Oxide ◽

Dependent Manner ◽

Microglia Cell ◽

The Central Nervous System ◽

Radical Generation ◽

Oxide Synthase ◽

Cell Medium ◽

Dose Dependent

The generation of ROS and lipid peroxidation has been considered to play an important role in the pathogenesis of chronic fluoride toxicity. In the present study, we observed that fluoride activated BV-2 microglia cell line by observing OX-42 expression in immunocytochemistry. Intracellular superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA), reactive oxygen species (ROS), superoxide anions (O2∙-), nitric oxide synthase (NOS), nitrotyrosine (NT) and nitric oxide (NO), NOS in cell medium were determined for oxidative stress assessment. Our study found that NaF of concentration from 5 to 20 mg/L can stimuli BV-2 cells to change into activated microglia displaying upregulated OX-42 expression. SOD activities significantly decreased in fluoride-treated BV-2 cells as compared with control, and MDA concentrations and contents of ROS andO2∙-increased in NaF-treated cells. Activities of NOS in cells and medium significantly increased with fluoride concentrations in a dose-dependent manner. NT concentrations also increased significantly in 10 and 50 mg/L NaF-treated cells compared with the control cells. Our present study demonstrated that toxic effects of fluoride on the central nervous system possibly partly ascribed to activiting of microglia, which enhanced oxidative stress induced by ROS and reactive nitrogen species.

Download Full-text

Methotrexate-Loaded Solid Lipid Nanoparticles: Protein Functionalization to Improve Brain Biodistribution

Pharmaceutics ◽

10.3390/pharmaceutics11020065 ◽

2019 ◽

Vol 11 (2) ◽

pp. 65 ◽

Cited By ~ 13

Author(s):

Elisabetta Muntoni ◽

Katia Martina ◽

Elisabetta Marini ◽

Marta Giorgis ◽

Loretta Lazzarato ◽

...

Keyword(s):

Blood Brain Barrier ◽

Solid Lipid Nanoparticles ◽

Lipid Nanoparticles ◽

Brain Barrier ◽

Target Tissue ◽

Solid Lipid ◽

Blood Brain ◽

The Central Nervous System

Glioblastoma is the most common and invasive primary tumor of the central nervous system and normally has a negative prognosis. Biodistribution in healthy animal models is an important preliminary study aimed at investigating the efficacy of chemotherapy, as it is mainly addressed towards residual cells after surgery in a region with an intact blood–brain barrier. Nanoparticles have emerged as versatile vectors that can overcome the blood–brain barrier. In this experimental work, solid lipid nanoparticles, prepared using fatty acid coacervation, have been loaded with an active lipophilic ester of cytotoxic drug methotrexate, and functionalized with either transferrin or insulin, two proteins whose receptors are abundantly expressed on the blood–brain barrier. Functionalization has been achieved by grafting a maleimide moiety onto the nanoparticle’s surface and exploiting its reactivity towards thiolated proteins. The nanoparticles have been tested in vitro on a blood–brain barrier cellular model and in vivo for biodistribution in Wistar rats. Drug metabolites, in particular 7-hydroxymethotrexate, have also been investigated in the animal model. The data obtained indicate that the functionalization of the nanoparticles improved their ability to overcome the blood–brain barrier when a PEG spacer between the proteins and the nanoparticle’s surface was used. This is probably because this method provided improved ligand–receptor interactions and selectivity for the target tissue.

Download Full-text

Evaluation of Quetiapine Fumarate and its Solid Lipid Nanoparticles as antipsychotic drug in rat model of schizophrenia

Biomedical Research and Therapy ◽

10.15419/bmrat.v4i08.203 ◽

2017 ◽

Vol 4 (08) ◽

pp. 1480 ◽

Cited By ~ 3

Author(s):

Said M. M. ◽

Gehan A. Elmenoufy

Keyword(s):

Side Effects ◽

Rat Model ◽

Solid Lipid Nanoparticles ◽

Lipid Nanoparticles ◽

Brain Regions ◽

Control Group ◽

High Dose ◽

Dependent Manner ◽

Quetiapine Fumarate ◽

Solid Lipid

Background: The present study compares the efficacy of quetiapine fumarate (QF) and QF-loaded solid lipid nanoparticles (QFSLN) as antipsychotic drugs for schizophrenia. Methods: To induce schizophrenia-like symptoms, a group of rats was injected intraperitoneally (i.p.) with ketamine (25mg/kg b.w.) for 1 week to establish a rat model of schizophrenia. The incidence of schizophrenic symptoms was estimated to be equivalent to the control group. To estimate the pronounced antipsychotic effect of QF, a low dose (LD) of 10 mg/kg b.w. and a high dose (HD) of 30 mg /kg b.w. were orally administrated to two groups of rats (designated L.QF and H.QF) for 3 weeks (2 weeks without ketamine injection; the last week with ketamine). To achieve the optimal therapeutic response of QF drug, 2 other groups of rats were administered orally the equivalent low and high doses of QF in its solid lipid nanoparticle form (L.QFSLN) and (H.QFSLN) for 3 weeks in the same manner. The treatments were given after 1 h of ketamine injection. To assess the effect of different doses of treatment on hyperlocomotion and cognitive impairment induced by ketamine, an open field test and passive avoidance test were conducted. In addition, excitatory and inhibitory amino acids, as well as catecholamines, were estimated in brain regions (cortex and hippocampus). The study was extended to estimate the side effects of different treatments on hepatorenal functions and lipid profile. Additionally, samples were subjected to immunohistochemical analysis. Results: QFSLN treatment showed enhanced effect over QF in a dose-dependent manner with minimal side effects in schizophrenic rats. In addition, immunohistochemical examinations of brain tissues confirmed the biochemical data.

Download Full-text

Antileishmanial activity of conventional and solid lipid nanoparticles of Amphotericin B on Leishmania major

Infectious Disorders - Drug Targets ◽

10.2174/1871526519666191015170627 ◽

2019 ◽

Vol 19 ◽

Author(s):

Shahrzad Soltani ◽

Hoda Mojiri -Forushani ◽

Sheyda Soltani ◽

Mehdi Sagha Kahvaz ◽

Masoud Foroutan

Keyword(s):

Amphotericin B ◽

Solid Lipid Nanoparticles ◽

Leishmania Major ◽

Colorimetric Assay ◽

Lipid Nanoparticles ◽

Antileishmanial Activity ◽

Control Group ◽

Dependent Manner ◽

Solid Lipid

Background: Obligate intracellular parasites of Leishmania genus belong to family Trypanosomatidae and more than twenty species causes this neglected vector-borne infection throughout the globe. The current study was aimed to assess the antileishmanial activity of Amphotericin B (AmB) and AmB formulated into solid lipid nanoparticles (SLNs) in vitro and in vivo. Materials and methods: In the present research, microemulsification and high shear homogenization methods were used to prepare SLNs. Leishmania major (L. major) promastigotes were cultured in RPMI 1640 and incubated for three time points of 24, 48 and 72 h at 25±1°C. Then, the MTT colorimetric assay was employed for obtaining of 50% inhibitory concentration (IC50). Finally, we evaluated the efficacy of AmB and AmB-SLN for the treatment of experimental cutaneous leishmaniasis (CL) in BALB/c mice. Results: The average diameter sizes of prepared AmB-SLN were <180 nm and monodisperse preparations with polydispersity index 0.21±0.29. The antileishmanial activity of AmB and AmB-SLN revealed a dose and time-dependent manner in vitro. The IC50 values of AmB (38.18±1.33, 25.06±2.00, and 13.87±0.61 μg/ml) and AmB-SLN (0.40±0.02, 0.26±0.02, and 0.14±0.01 μg/ml) were estimated after 24, 48 and 72 hours, respectively. In all BALB/c treatment groups, the diameter of lesions were significantly smaller than the control group. Conclusion: Discovery of new effective drugs based on nanocarriers, such as SLN, is practical and opens a new window for the treatment of CL. More studies are needed in the future.

Download Full-text