Highly Stabilized Curcumin Nanoparticles Tested in an In Vitro Blood–Brain Barrier Model and in Alzheimer’s Disease Tg2576 Mice

Cheng, K.-K.M.; Yeung, Chin Fung; Ho, Shuk Wai; Chow, Shing Fung; Chow, Albert H.L.; Baum, Larry

doi:10.1208/s12248-012-9444-4

Cited by 256 publications

(157 citation statements)

References 53 publications

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“…The t 1 / 2 of curcumin in mPEG-HPMA-Bz and Triton X-100 micelles (777±87 and 1100± 95 h, respectively) is about 300-500 times higher than that of free curcumin in aqueous buffer (2.5 h). This shows that in line with reported data nanoformulations substantially protect curcumin against degradation (42)(43)(44).…”

Section: Degradation Of Curcumin (As Curcuminoid Mixture) Loaded In Msupporting

confidence: 92%

A Kinetic Degradation Study of Curcumin in Its Free Form and Loaded in Polymeric Micelles

Naksuriya

Steenbergen

Toraño

et al. 2016

AAPS J

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Abstract. Curcumin, a phenolic compound, possesses many pharmacological activities and is under clinical evaluation to treat different diseases. However, conflicting data about its stability have been reported. In this study, the kinetic degradation of curcumin from a natural curcuminoid mixture under various conditions (pH, temperature, and dielectric constant of the medium) was investigated. Moreover, the degradation of pure curcumin at some selected conditions was also determined. To fully solubilize curcumin and to prevent precipitation of curcumin that occurs when low concentrations of co-solvent are present, a 50:50 (v/v) aqueous buffer/methanol mixture was used as standard medium to study its degradation kinetics. The results showed that degradation of curcumin both as pure compound and present in the curcuminoid mixture followed first order kinetic reaction. It was further shown that an increasing pH, temperature, and dielectric constant of the medium resulted in an increase in the degradation rate. Curcumin showed rapid degradation due to autoxidation in aqueous buffer pH=8.0 with a rate constant of 280×10 -3 h -1, corresponding with a half-life (t 1/2 ) of 2.5 h. Dioxygenated bicyclopentadione was identified as the final degradation product. Importantly, curcumin loaded as curcuminoid mixture in ω-methoxy poly (ethylene glycol)-b-(N-(2-benzoyloxypropyl) methacrylamide) (mPEG-HPMA-Bz) polymeric micelles and in Triton X-100 micelles was about 300-500 times more stable than in aqueous buffer. Therefore, loading of curcumin into polymeric micelles is a promising approach to stabilize this compound and develop formulations suitable for further pharmaceutical and clinical studies.

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Section: Degradation Of Curcumin (As Curcuminoid Mixture) Loaded In Msupporting

confidence: 92%

A Kinetic Degradation Study of Curcumin in Its Free Form and Loaded in Polymeric Micelles

Naksuriya

Steenbergen

Toraño

et al. 2016

AAPS J

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“…The Radial Arm MazeDescription-The RAM paradigm (48,49) was conducted using a Plexiglass maze whose eight arms (35 cm ϫ 8 cm ϫ 8 cm) are connected by removable guillotine doors to a circular central chamber (21 cm diameter, Fig. 1A).…”

Section: Methodsmentioning

confidence: 99%

Dynamics of Hippocampal Protein Expression During Long-term Spatial Memory Formation

Borovok

Nesher

Levin

et al. 2016

Molecular & Cellular Proteomics

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Spatial memory depends on the hippocampus, which is particularly vulnerable to aging. This vulnerability has implications for the impairment of navigation capacities in older people, who may show a marked drop in performance of spatial tasks with advancing age. Contemporary understanding of long-term memory formation relies on molecular mechanisms underlying long-term synaptic plasticity. With memory acquisition, activity-dependent changes occurring in synapses initiate multiple signal transduction pathways enhancing protein turnover. This enhancement facilitates de novo synthesis of plasticity related proteins, crucial factors for establishing persistent long-term synaptic plasticity and forming memory engrams. Extensive studies have been performed to elucidate molecular mechanisms of memory traces formation; however, the identity of plasticity related proteins is still evasive. In this study, we investigated protein turnover in mouse hippocampus during long-term spatial memory formation using the reference memory version of radial arm maze (RAM) paradigm. We identified 1592 proteins, which exhibited a complex picture of expression changes during spatial memory formation. Variable linear decomposition reduced significantly data dimensionality and enriched three principal factors responsible for variance of memory-related protein levels at (1) the initial phase of memory acquisition (165 proteins), (2) during the steep learning improvement (148 proteins), and (3) the final phase of the learning curve (123 proteins). Gene ontology and signaling pathways analysis revealed a clear correlation between memory improvement and learning phasecurbed expression profiles of proteins belonging to specific functional categories. We found differential enrichment of (1) Long-term synaptic plasticity is considered a cellular correlate of long-term memory (LTM) 1 . Contemporary understanding of memory formation is based on the initiation and maintenance of long-term synaptic plasticity (1-4), for which de novo protein synthesis is a vital requirement. De novo protein synthesis itself is secondary to activity-dependent changes in synapses that occur during learning processes. These activity changes trigger post-translational modifications of proteins initiating and sustaining multiple signal transduction pathways. In turn, these signaling pathways regulate changes in synaptic strength and connectivity by governing gene expression and protein translation (5-13). Depending on time elapsed since triggering of long-term synaptic plasticity, protein synthesis may be limited to the dendrites directly involved in the plasticity processes (14 -18). Multiple synaptic From the ‡Department

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“…The drug was associated with albumin nanoparticles engulfing CDs (β-CD, HPβCD or SBE7-β-CD) for nose to brain delivery and were successfully tested on ex vivo sheep nasal mucosae exhibiting enhanced mucosal adhesion and permeation abilities compared to albumin nanoparticles alone [73]. Drug delivery to the brain, crossing the BBB, to treat AD was assessed by Cheng et al (2013) by means of the development of curcumin nanoparticles associated with HPβCD [76]. In this study the curative effect of curcumin was evaluated while HPβCD was solely used for its cryoprotective efficiency.…”

Section: Alzheimer's Diseasementioning

confidence: 99%

Cyclodextrins as Emerging Therapeutic Tools in the Treatment of Cholesterol-Associated Vascular and Neurodegenerative Diseases

et al. 2016

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Cardiovascular diseases, like atherosclerosis, and neurodegenerative diseases affecting the central nervous system (CNS) are closely linked to alterations of cholesterol metabolism. Therefore, innovative pharmacological approaches aiming at counteracting cholesterol imbalance display promising therapeutic potential. However, these approaches need to take into account the existence of biological barriers such as intestinal and blood-brain barriers which participate in the organ homeostasis and are major defense systems against xenobiotics. Interest in cyclodextrins (CDs) as medicinal agents has increased continuously based on their ability to actively extract lipids from cell membranes and to provide suitable carrier system for drug delivery. Many novel CD derivatives are constantly generated with the objective to improve CD bioavailability, biocompatibility and therapeutic outcomes. Newly designed drug formulation complexes incorporating CDs as drug carriers have demonstrated better efficiency in treating cardiovascular and neurodegenerative diseases. CD-based therapies as cholesterol-sequestrating agent have recently demonstrated promising advances with KLEPTOSE ® CRYSMEB in atherosclerosis as well as with the 2-hydroxypropyl-β-cyclodextrin (HPβCD) in clinical trials for Niemann-Pick type C disease. Based on this success, many investigations evaluating the therapeutical beneficial of CDs in Alzheimer's, Parkinson's and Huntington's diseases are currently on-going.

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Highly Stabilized Curcumin Nanoparticles Tested in an In Vitro Blood–Brain Barrier Model and in Alzheimer’s Disease Tg2576 Mice

Cited by 256 publications

References 53 publications

A Kinetic Degradation Study of Curcumin in Its Free Form and Loaded in Polymeric Micelles

A Kinetic Degradation Study of Curcumin in Its Free Form and Loaded in Polymeric Micelles

Dynamics of Hippocampal Protein Expression During Long-term Spatial Memory Formation

Cyclodextrins as Emerging Therapeutic Tools in the Treatment of Cholesterol-Associated Vascular and Neurodegenerative Diseases

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