With the objective to formulate multifunctional nanosized liposomes to target amyloid deposits in Alzheimer Disease (AD) brains, a lipid–PEG–curcumin derivative was synthesized and characterized. ...Multifunctional liposomes incorporating the curcumin derivative and additionally decorated with a Blood Brain Barrier (BBB) transport mediator (anti-Transferin antibody) were prepared and characterized. The fluorescence intensity of curcumin derivative was found to increase notably when the curcumin moiety was in the form of a diisopropylethylamine (DIPEA) salt. Both curcumin-derivative liposomes and curcumin-derivative Anti-TrF liposomes showed a high affinity for the amyloid deposits, on post-mortem brains samples of AD patients. The ability of both liposomes to delay Aβ1-42 peptide aggregation was confirmed by Thioflavin assay. However, the decoration of the curcumin-derivative liposomes with the Anti-TrF improved significantly the intake by the BBB cellular model. Results verify that the attachment of an antibody on the curcumin-liposome surface does not block deposit staining or prevention of Aβ aggregation, while the presence of the curcumin–PEG–lipid conjugate does not reduce their brain-targeting capability substantially, proving the potential of such multifunctional NLs for application in Alzheimer disease treatment and diagnosis.
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•Multifunctional nanoliposomes (NLs) to target both: Amyloid deposits and BBB.•Inhibitory activity on Aβ aggregation and Amyloid plaque staining ability.•Brain targeting potential demonstrated (in vitro).•Conclusion: Developed NLs are potential theragnostic systems for AD.
Turmeric is a curry spice that originated from India, which has attracted great interest in recent decades because it contains bioactive curcuminoids (curcumin, demethoxycurcumin, and ...bisdemethoxycurcumin). Curcumin (1,7-bis-(4-hydroxy-3-methoxyphenyl)-hepta-1,6-diene-3,5-dione), a lipophilic polyphenol may work as an anticancer, antibiotic, anti-inflammatory, and anti-aging agent as suggested by several in vitro, in vivo studies and clinical trials. However, poor aqueous solubility, bioavailability, and pharmacokinetic profiles limit curcumin's therapeutic usage. To address these issues, several curcumin formulations have been developed. However, suboptimal sample preparation and analysis methodologies often hamper the accurate evaluation of bioactivities and their clinical efficacy. This review summarizes recent research on biological, pharmaceutical, and analytical aspects of the curcumin. Various formulation techniques and corresponding clinical trials and in vivo outcomes are discussed. A detailed comparison of different sample preparation (ultrasonic, pressurized liquid extraction, microwave, reflux) and analytical (FT-IR, FT-NIR, FT-Raman, UV, NMR, HPTLC, HPLC, and LC-MS/MS) methodologies used for the extraction and quantification of curcuminoids in different matrices, is presented. Application of optimal sample preparation, chromatographic separation, and detection methodologies will significantly improve the assessment of different formulations and biological activities of curcuminoids.
The pathological aggregation and accumulation of tau, a microtubule-associated protein, is a common feature amongst more than 18 different neurodegenerative diseases that are collectively known as ...tauopathies. Recently, it has been demonstrated that the soluble and hydrophobic tau oligomers are highly toxic in vitro due to their capacity towards seeding tau misfolding, thereby propagating the tau pathology seen across different neurodegenerative diseases. Modulating the aggregation state of tau oligomers through the use of small molecules could be a useful therapeutic strategy to target their toxicity, regardless of other factors involved in their formation. In this study, we screened and tested a small library of newly synthesized curcumin derivatives against preformed recombinant tau oligomers. Our results show that the curcumin derivatives affect and modulate the tau oligomer aggregation pathways, converting to a more aggregated non-toxic state as assessed in the human neuroblastoma SH-SY5Y cell line and primary cortical neuron cultures. These results provide insight into tau aggregation and may become a basis for the discovery of new therapeutic agents, as well as advance the diagnostic field for the detection of toxic tau oligomers.
Objectives
Nanotechnology‐based drug delivery systems can resolve the poor bioavailability issue allied with curcumin. The therapeutic potential of curcumin can be enhanced by making nanocomposite ...preparation of curcumin with metal oxide nanoparticles, poly lactic‐co‐glycolic acid (PLGA) nanoparticles and solid lipid nanoparticles that increases its bioavailability in the tissue.
Key findings
Curcumin has manifold therapeutic effects which include antidiabetic, antihypertensive, anticancer, anti‐inflammatory and antimicrobial properties. Curcumin can inhibit diabetes, heavy metal and stress‐induced hypertension with its antioxidant, chelating and inhibitory effects on the pathways that lead to hypertension. Curcumin is an anticancer agent that can prevent abnormal cell proliferation. Nanocurcumin is an improved form of curcumin with enhanced therapeutic properties due to improved delivery to the diseased tissue, better internalization and reduced systemic elimination.
Summary
Curcumin has multiple pharmacologic effects, but its poor bioavailability reduces its therapeutic effects. By conjugating curcumin to metal oxide nanoparticles or encapsulation in lipid nanoparticles, dendrimers, nanogels and polymeric nanoparticles, the water solubility and bioavailability of curcumin can be improved and thus increase its pharmacological effectiveness.
Water-soluble curcumin (CCM)-loaded human serum albumin (HSA) nanoparticles (CCM-HSA-NPs) and its improved antitumor activity.
Curcumin (CCM), a yellow natural polyphenol extracted from turmeric ...(Curcuma longa), has potent anti-cancer properties as has been demonstrated in various human cancer cells. However, the widespread clinical application of this efficient agent in cancer and other diseases has been limited by its poor aqueous solubility and bioavailability. In this study, we prepared novel CCM-loaded human serum albumin (HSA) nanoparticles (CCM-HSA-NPs) for intravenous administration using albumin bound technology. Field emission scanning electron microscopy (FE-SEM) and dynamic light scattering (DLS) investigation confirmed a narrow size distribution in the 130–150nm range. Furthermore, CCM-HSA-NPs showed much greater water solubility (300-fold) than free CCM, and on storage, the biological activity of CCM-HSA-NPs was preserved with negligible activity loss. In vivo distributions and vascular endothelial cells transport studies demonstrated the superiority of CCM-HSA-NPs over CCM. Amounts of CCM in tumors after treatment with CCM-HSA-NPs were about 14 times higher at 1h after injection than that achieved by CCM. Furthermore, vascular endothelial cell binding of CCM increased 5.5-fold, and transport of CCM across a vascular endothelial cell monolayer by Transwell testing was 7.7-fold greater for CCM-HSA-NPs than CCM. Finally, in vivo antitumor tests revealed that CCM-HSA-NPs (10 or 20mg/kg) had a greater therapeutic effect (50% or 66% tumor growth inhibition vs. PBS-treated controls) than CCM (18% inhibition vs. controls) in tumor xenograft HCT116 models without inducing toxicity. We attribute this potent antitumor activity of CCM-HSA-NPs to enhanced water solubility, increased accumulation in tumors, and an ability to traverse vascular endothelial cell.
The severity of the recent pandemic and the absence of any specific medication impelled the identification of existing drugs with potential in the treatment of Coronavirus disease-2019 (COVID-19), ...caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). Curcumin, known for its pharmacological abilities especially as an anti-inflammatory agent, can be hypothesized as a potential candidate in the therapeutic regimen. COVID-19 has an assorted range of pathophysiological consequences, including pulmonary damage, elevated inflammatory response, coagulopathy, and multi-organ damage. This review summarizes the several evidences for the pharmacological benefits of curcumin in COVID-19-associated clinical manifestations. Curcumin can be appraised to hinder cellular entry, replication of SARS-CoV-2, and to prevent and repair COVID-19-associated damage of pneumocytes, renal cells, cardiomyocytes, hematopoietic stem cells, etc. The modulation and protective effect of curcumin on cytokine storm-related disorders are also discussed. Collectively, this review provides grounds for its clinical evaluation in the therapeutic management of SARS-CoV-2 infection.
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Curcumin, a polyphenol derived from the rhizome of the naturally occurring plant Curcuma longa, has various pharmacological actions such as antioxidant and anti-inflammatory effects. In this paper, ...we evaluated the role of its internal metabolite, curcumin β-D-glucuronide (curcumin monoglucuronide, CMG), by investigating curcumin kinetics and metabolism in the blood. Firstly, we orally administered highly bioavailable curcumin to rats to elucidate its kinetics, and observed not only the free-form of curcumin, but also, curcumin in a conjugated form, within the portal vein. We confirmed that curcumin is conjugated when it passes through the intestinal wall. CMG, one of the metabolites, was then orally administered to rats. Despite its high aqueous solubility compared to free-form curcumin, it was not well absorbed. In addition, CMG was injected intravenously into rats in order to assess its metabolic behavior in the blood. Interestingly, high levels of free-form curcumin, thought to be sufficiently high to be pharmacologically active, were observed. The in vivo antitumor effects of CMG following intravenous injection were then evaluated in tumor-bearing mice with the HCT116 human colon cancer cell line. The tumor volume within the CMG group was significantly less than that of the control group. Moreover, there was no significant loss of body weight in the CMG group compared to the control group. These results suggest that CMG could be used as an anticancer agent without the serious side effects that most anticancer agents have.
Cancer is the second leading cause of death in the United States. Conventional therapies cause widespread systemic toxicity and lead to serious side effects which prohibit their long term use. ...Additionally, in many circumstances tumor resistance and recurrence is commonly observed. Therefore, there is an urgent need to identify suitable anticancer therapies that are highly precise with minimal side effects. Curcumin is a natural polyphenol molecule derived from the Curcuma longa plant which exhibits anticancer, chemopreventive, chemo- and radio-sensitization properties. Curcumin's widespread availability, safety, low cost and multiple cancer fighting functions justify its development as a drug for cancer treatment. However, various basic and clinical studies elucidate curcumin's limited efficacy due to its low solubility, high rate of metabolism, poor bioavailability and pharmacokinetics. A growing list of nanomedicine(s) using first line therapeutic drugs have been approved or are under consideration by the Food and Drug Administration (FDA) to improve human health. These nanotechnology strategies may help to overcome challenges and ease the translation of curcumin from bench to clinical application. Prominent research is reviewed which shows that advanced drug delivery of curcumin (curcumin nanoformulations or curcumin nanomedicine) is able to leverage therapeutic benefits by improving bioavailability and pharmacokinetics which in turn improves binding, internalization and targeting of tumor(s). Outcomes using these novel drug delivery systems have been discussed in detail. This review also describes the tumor-specific drug delivery system(s) that can be highly effective in destroying tumors. Such new approaches are expected to lead to clinical trials and to improve cancer therapeutics.
An effective drug nanocarrier was developed on the basis of a quaternized aminated chitosan (Q-AmCs) derivative for the efficient encapsulation and slow release of the curcumin (Cur)-drug. A simple ...ionic gelation method was conducted to formulate Q-AmCs nanoparticles (NPs), using different ratios of sodium tripolyphosphate (TPP) as an ionic crosslinker. Various characterization tools were employed to investigate the structure, surface morphology, and thermal properties of the formulated nanoparticles. The formulated Q-AmCs NPs displayed a smaller particle size of 162 ± 9.10 nm, and higher surface positive charges, with a maximum potential of +48.3 mV, compared to native aminated chitosan (AmCs) NPs (231 ± 7.14 nm, +32.8 mV). The Cur-drug encapsulation efficiency was greatly improved and reached a maximum value of 94.4 ± 0.91%, compared to 75.0 ± 1.13% for AmCs NPs. Moreover, the in vitro Cur-release profile was investigated under the conditions of simulated gastric fluid SGF; pH 1.2 and simulated colon fluid SCF; pH 7.4. For Q-AmCs NPs, the Cur-release rate was meaningfully decreased, and recorded a cumulative release value of 54.0% at pH 7.4, compared to 73.0% for AmCs NPs. The formulated nanoparticles exhibited acceptable biocompatibility and biodegradability. These findings emphasize that Q-AmCs NPs have an outstanding potential for the delivery and slow release of anticancer drugs.
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