scholarly journals Targeting the Endocannabinoid/CB1 Receptor System For Treating Major Depression Through Antidepressant Activities of Curcumin and Dexanabinol-Loaded Solid Lipid Nanoparticles

2017 ◽  
Vol 42 (6) ◽  
pp. 2281-2294 ◽  
Author(s):  
Xiaolie He ◽  
Li Yang ◽  
Mei Wang ◽  
Xizhen Zhuang ◽  
Ruiqi Huang ◽  
...  

Background/Aims: This study investigated the underlying mechanisms of the antidepressant effects of curcumin and dexanabinol-loaded solid lipid nanoparticles in corticosterone-induced cell and mice depression models. Methods: Curcumin and dexanabinol-loaded solid lipid nanoparticles (Cur/SLNs-HU-211) were synthesized via an emulsifcation and low-temperature solidification method. Antidepressant activities of nanoparticles in a corticosterone-induced major depression model were investigated by MTT assay, cellular uptake by flow cytometry, behaviour by Forced Swimming Test and rotarod test, neurotransmitters by High Performance Liquid Chromatography, Western blotting, qPCR and immunofluorescence. Results: Treatment with Cur/SLNs-HU-211 induced greater dopamine (DA)/5-hydroxytryptamine (5-HT) release with reduced corticosterone-induced apoptotic cell death in PC12 cells. Additionally, in vivo Cur/SLNs-HU-211 significantly induced recovery from depressive behaviour with increased DA/5-HT levels, CB1 mRNA levels and CB1, p-MEK1 and p-ERK1/2 protein expression levels in the hippocampus and striatum. Cur/SLNs-HU-211 improved CB1 expression and inspired the proliferation of astrocytes in the hippocampus and striatum, exerted neuroprotective effects by preventing corticosterone -induced BDNF/NeuN expression reduction. Conclusion: Our study implies that Cur/SLNs-HU-211 may be a useful approach for treatment of major depression.

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Hee-Sook Jun ◽  
Gongdeuk Bae ◽  
Young Tag Ko ◽  
Yoon Sin Oh

Exendin-4 (Ex-4), a peptide of glucagon-like peptide-1 receptor agonist, is a potent insulinotropic agent and alternative drug delivery systems to increase therapeutic utility have been explored. We developed exendin-4-encapsulated solid lipid nanoparticles (Eudragit Ex-4 SLNs) and compared the effects of Eudragit Ex-4 SLNs with those of native Ex-4 on INS-1 cells. We observed no significant toxic effects of nanoparticles at concentrations from 1 nM to 100 nM. Similar to Ex-4, Eudragit Ex-4 SLNs stimulated the production of cyclic AMP at 10 nM. Moreover, unlike treatment with the vehicle, treatment with 10 nM Eudragit Ex-4 SLNs increased insulin mRNA levels and insulin secretion. These insulinotropic effects of Eudragit Ex-4 SLNs were comparable to those of Ex-4. Thus, ourin vitroresults suggest that the biological effects of Eudragit Ex-4 SLNs are similar to those of Ex-4, and furtherin vivopharmacokinetic studies are required to propose an alternative sustained release drug system.


2020 ◽  
Vol 20 (13) ◽  
pp. 1044-1052
Author(s):  
Nasrin Abbasi Gharibkandi ◽  
Sajjad Molavipordanjani ◽  
Jafar Akbari ◽  
Seyed Jalal Hosseinimehr

Background: Solid Lipid Nanoparticles (SLNs) possess unique in vivo features such as high resistivity, bioavailability, and habitation at the target site. Coating nanoparticles with polymers such as chitosan greatly affects their pharmacokinetic behavior, stability, tissue uptake, and controlled drug delivery. The aim of this study was to prepare and evaluate the biodistribution of 99mTc-labeled SLNs and chitosan modified SLNs in mice. Methods: 99mTc-oxine was prepared and utilized to radiolabel pre-papered SLNs or chitosan coated SLNs. After purification of radiolabeled SLNs (99mTc-SLNs) and radiolabeled chitosan-coated SLNs (99mTc-Chi-SLNs) using Amicon filter, they were injected into BALB/c mice to evaluate their biodistribution patterns. In addition, nanoparticles were characterized using Transmission Electron Microscopy (TEM), Fourier-transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), X-ray Powder Diffraction (XRD) and Dynamic Light Scattering (DLS). Results: 99mTc-oxine with high radiochemical purity (RCP~100%) and stability (RCP > 97% at 24 h) was used to provide 99mTc-SLNs and 99mTc-Chi-SLNs with high initial RCP (100%). TEM image and DLS data suggest 99mTc- SLNs susceptibility to aggregation. To that end, the main portion of 99mTc-SLNs radioactivity accumulates in the liver and intestines, while 99mTc-Chi-SLNs sequesters in the liver, intestines and kidneys. The blood radioactivity of 99mTc-Chi-SLNs was higher than that of 99mTc-SLNs by 7.5, 3.17 and 3.5 folds at 1, 4 and 8 h post-injection. 99mTc- Chi-SLNs uptake in the kidneys in comparison with 99mTc-SLNs was higher by 37.48, 5.84 and 11 folds at 1, 4 and 8h. Conclusion: The chitosan layer on the surface of 99mTc-Chi-SLNs reduces lipophilicity in comparison with 99mTc- SLNs. Therefore, 99mTc-Chi-SLNs are less susceptible to aggregation, which leads to their lower liver uptake and higher kidney uptake and blood concentration.


2013 ◽  
Vol 10 (6) ◽  
pp. 656-666 ◽  
Author(s):  
Sandipan Dasgupta ◽  
Surajit Ghosh ◽  
Subhabrata Ray ◽  
Bhaskar Mazumder

Author(s):  
Rosa Maria Iacobazzi ◽  
Fabio Vischio ◽  
Ilaria Arduino ◽  
Fabio Canepa ◽  
Valentino Laquintana ◽  
...  

Author(s):  
Sonia Pandey ◽  
Farhinbanu Shaikh ◽  
Arti Gupta ◽  
Purnima Tripathi ◽  
Jitendra Singh Yadav

Solid lipid nanoparticles are one of the developed technologies for addressing the bioavailability and targeting issues of drug delivery. In this review article, we attempted to incorporate all the essential details of SLNs like various methods of preparation, different models of SLNs, updated characterization methods, in-vivo behavior (Uptake), their applications, route of administration as well as advancements taken place in the field of delivery of biological drugs like gene vector, new adjuvant for vaccines, protein, and peptide with SLNs. Surface modified SLNs hold excellent potential for targeted and controlled drug delivery which is discussed and summarized. Based on the available data, the future success of SLNs is widened because they could be easily fabricated with various functionalities which would display enormous potential for targeting and diagnosing various diseases. This review would help the budding researchers to find out the unexplored areas of SLNs with the present discussion that reframes the potential of SLNs by gathering the various research findings of SLNs in tabular form along with the approved patent technologies of SLNs.


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