Formulation and evaluation of nano lipid formulation containing CNS acting drug: molecular docking, <i>in-vitro</i> assessment and bioactivity detail in rats

Alam, M. Mumtaz; Najmi, Abul Kalam; Ahmad, Iqbal; Ahmad, Farhan Jalees; Akhtar, Jawaid; Imam, Syed Sarim; Akhtar, Mohd

doi:10.1080/21691401.2018.1451873

Cited by 34 publications

(16 citation statements)

References 41 publications

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“…TQ is a lipophilic compound with molecular weight of 164.2 42 , log P of 2.54 43 and a low aqueous solubility of about 500 μg/ml 44 . TQ possesses antioxidant 45,46 , anti-inflammatory 47,48 , anti-hyperlipidemic 49 , anti-depressant 50 and antimicrobial activities 51 , and its use in combination with chemotherapeutic agents reduces their side effects 52,53 . TQ possesses antiproliferative activity on various types of cancer including colorectal carcinoma 54 , and was found to induce cell cycle arrest and apoptosis in HCT-116 human colon cancer cells 55 .…”

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confidence: 99%

Novel thymoquinone lipidic core nanocapsules with anisamide-polymethacrylate shell for colon cancer cells overexpressing sigma receptors

Ramzy

Metwally

Nasr

et al. 2020

Sci Rep

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the biggest challenge in colorectal cancer therapy is to avoid intestinal drug absorption before reaching the colon, while focusing on tumor specific delivery with high local concentration and minimal toxicity. in our work, thymoquinone (tQ)-loaded polymeric nanocapsules were prepared using the nanoprecipitation technique using Eudragit S100 as polymeric shell. Conjugation of anisamide as a targeting ligand for sigma receptors overexpressed by colon cancer cells to Eudragit S100 was carried out via carbodiimide coupling reaction, and was confirmed by thin layer chromatography and 1 H-nMR. tQ nanocapsules were characterized for particle size, surface morphology, zeta potential, entrapment efficiency % (EE%), in vitro drug release and physical stability. A cytotoxicity study on three colon cancer cell lines (HT-29, HCT-116, Caco-2) was performed. Results revealed that the polymeric nanocapsules were successfully prepared, and the in vitro characterization showed a suitable size, zeta potential, EE% and physical stability. TQ exhibited a delayed release pattern from the nanocapsules in vitro. Anisamide-targeted tQ nanocapsules showed higher cytotoxicity against HT-29 cells overexpressing sigma receptors compared to their non-targeted counterparts and free TQ after incubation for 48 h, hence delineating anisamide as a promising ligand for active colon cancer targeting. Sigma receptors are expressed in normal cells of various organs including brain, kidney, liver, immune, endocrine and reproductive organ 1,2. Two distinguished subtypes were recognized and known as sigma-1 and sigma-2 3. Neurosteroids are the likely endogenous ligands for sigma-1 receptors 4 , and N,N-dimethyltryptamine; a natural alkaloid, was also found to be an endogenous ligand for sigma-1 receptors 5,6. A correlation between sigma receptors and diseases such as Parkinson's, Alzheimer's disease and cancer has been proposed 7 , and ligands for sigma-1 receptor were proven to improve various neurodegenerative disorders 8. Sigma-2 receptor is thought to be crucial for cell morphology, survival and differentiation 9. Sigma receptors are overexpressed in cancer cells of various organs 10 including cancers of the brain 11 , lung 12,13 , breast 14 , prostate gland 15 , kidney and colon 16. The tumor environment characterized by oxidative stress, hypoxia, low pH and insufficient supply of glucose and amino acids mediates disruption of endoplasmic reticulum protein folding. This in turn contributes to sigma-1 receptors activation to promote cell survival 7,17. In addition, sigma-2 receptors upregulation in cancerous tissues compared to healthy ones has been widely demonstrated 18,19. Benzamide derivatives demonstrate a high affinity towards sigma receptors 20-22. Anisamide (AA); a small molecular weight benzamide derivative was proven to exhibit high affinity for sigma receptors 23-25. In a review article previously published by our team the use of AA as a targeting ligand in several drug delivery systems was detailed 26. AA-functionalized doxorubicin-loade...

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confidence: 99%

Novel thymoquinone lipidic core nanocapsules with anisamide-polymethacrylate shell for colon cancer cells overexpressing sigma receptors

Ramzy

Metwally

Nasr

et al. 2020

Sci Rep

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“…As per our earlier published work, thymoquinone loaded Solid lipid nanoparticles (TQSLN) Formulation were prepared and characterized [22]. In the present study thymoquinone loaded Solid lipid nanoparticles (TQSLN) was prepared and was subjected for visual observation, particle size, zeta potential, transmission electron microscopy (TEM) and differential scanning calorimetry (DSC).…”

Section: Thymoquinone Loaded Solid Lipid Nanoparticles (Tqsln) Formulmentioning

confidence: 91%

“…Researchers have shown greater interest in the development of solid lipid nano particle (SLNs) due to their unique structure, properties and biocompatibility [21]. Recently, a formulation of thymoquinone solid lipid nanoparticle was developed to enhance the solubility and bioavailability of conventional thymoquinone suspension and studied in unpredictable chronic mild stress models of depression [22]. Thus, the purpose of the present study was to evaluate the effect of thymoquinone solid lipid nanoparticle (TQSLN) in depression model of rats and study its mechanism via indoleamine 2, 3-dioxygenase pathway.…”

Section: Introductionmentioning

confidence: 99%

Thymoquinone Loaded Solid Lipid Nanoparticles Demonstrated Antidepressant-Like Activity in Rats via Indoleamine 2, 3- Dioxygenase Pathway

et al. 2020

Self Cite

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The World Health Organization (WHO) has ranked depression the 4th leading cause of disability worldwide. Thymoquinone (TQ), is an active constituent of Nigella sativa having various medicinal properties but has poor solubility and bioavailability. This problem was overcome by developing nanoformulation of TQ. Previously TQ reported good antioxidant and anti-inflammatory effects. Recently TQ’s anti-depressant effect was demonstrated. However, the mechanisms underlying the antidepressant effect of TQ still needs evaluation. Activation of Indoleamine-2,3-dioxygenase (IDO), (an enzyme that participates in the tryptophan metabolism), leads to a decrease of serotonin (5-HT) levels. The expression of this enzyme is associated with immune system activation, which has been proposed as a common mechanism that links depression. The present study was performed in stressed animals where hippocampal levels of pro-inflammatory cytokines (IL-6 and TNF α levels), brain derived neurotropic factor (BDNF) and hippocampal kynurenine (KYN), tryptophan (TRP) and serotonin (5-HT) levels were estimated. Treatment with TQ solid lipid nanoparticles (TQSLN 20 mg/kg p.o) and TQ suspension (20 mg/kg p.o) demonstrated antidepressant-like activity in chronic forced-swim stress model. Further, it reduced the elevated hippocampal IL-6 & TNFα and reversed the increased activity of IDO as measured by ratio of hippocampal KYN/TRP and 5HT/TRP in stressed rats. The results of the present study confirm anti-inflammatory and neuroprotective effects of TQ which may be associated with 5-HT pathway. Thus, the present study offers a newer approach to reduce symptoms of depression using TQSLN. Our results are preliminary, further research is needed for more conclusive view.

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“…Alam et al [ 34 ] studied the possible effect of TQ-loaded solid lipid nano particles (TQ-SLN) on the brain, comparing it to free TQ through the determination of a modified forced swim test, tail suspension test, and locomotor activities in rats. They found that TQ-SLN increased TQ delivery to brain tissues faster than free TQ, as demonstrated by determination of 5 hydroxytryptamine, dopamine, and norepinephrine levels in the brain ( Figure 4 ).…”

Section: Biological Activities Of Thymoquinone Nanoformulationmentioning

confidence: 99%

Protective Roles of Thymoquinone Nanoformulations: Potential Nanonutraceuticals in Human Diseases

El‐Far

Jaouni

et al. 2018

Nutrients

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The focus on nanotechnology for improved bioavailability and drug delivery is of increasing importance for control of different human diseases. Therefore, numerous nanoformulations have been developed for the oral bioavailability of different drugs. This review introduces applications of nanomedicine to enhance the biological activities of thymoquinone (TQ) to control different diseases in several in vivo studies as a preliminary investigation for human disease treatment with nano-TQ. Nano-TQ effectively augments the anticancer roles of doxorubicin by upregulation of P53 and downregulation of Bcl2 and potentiates paclitaxel’s apoptosis in MCF-7 breast cancer cells. Moreover, nano-TQ protects against diabetes, inflammation, CNS, and hepatotoxicity, mainly by enhancement of organs’ antioxidant status. We summarize the pros and cons of several FDA approved nanoparticle-based therapeutics and discuss the roadblocks in clinical translation, along with potential nano-TQ strategies to overcome these roadblocks. From this review, we can conclude that nano-TQ may be considered as a promising nutraceutical for human health.

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Formulation and evaluation of nano lipid formulation containing CNS acting drug: molecular docking, in-vitro assessment and bioactivity detail in rats

Cited by 34 publications

References 41 publications

Novel thymoquinone lipidic core nanocapsules with anisamide-polymethacrylate shell for colon cancer cells overexpressing sigma receptors

Novel thymoquinone lipidic core nanocapsules with anisamide-polymethacrylate shell for colon cancer cells overexpressing sigma receptors

Thymoquinone Loaded Solid Lipid Nanoparticles Demonstrated Antidepressant-Like Activity in Rats via Indoleamine 2, 3- Dioxygenase Pathway

Protective Roles of Thymoquinone Nanoformulations: Potential Nanonutraceuticals in Human Diseases

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