Albumin nanoparticles carrying cyclodextrins for nasal delivery of the anti-Alzheimer drug tacrine

Luppi, Barbara; Bigucci, Federica; Corace, Giuseppe; Delucca, A.; Cerchiara, Teresa; Sorrenti, Milena; Catenacci, Laura; Pietra, Anna Maria Di; Zecchi, Vittorio

doi:10.1016/j.ejps.2011.10.002

Cited by 114 publications

(47 citation statements)

References 25 publications

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“…This was the case for tacrine, an acetylcholine-esterase inhibitor approved for the treatment of AD exhibiting low bioavailability. 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].…”

Section: Alzheimer's Diseasementioning

confidence: 99%

“…Cholesterol depletion [11,12] Methyl-β-CD Cholesterol depletion [12] HPβCD Cholesterol depletion [13,[53][54][55][56] Reduces inflammation and lowers atherosclerotic lesion formation, reduces amounts of cholesterol crystals in atherosclerotic plaques [13] Niemann-Pick type C SBE7-β-CD Nasal delivery system for brain targeting, decreases Aβ-induced neurotoxicity in rat hippocampus [73], associated with tacrine/albumin Improved brain delivery and neurogenic drug efficacy [77], coupled with allopregnanolone Table 2. Cont.…”

Section: Cds As Drug Delivery Systemsmentioning

confidence: 99%

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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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Section: Alzheimer's Diseasementioning

confidence: 99%

Section: Cds As Drug Delivery Systemsmentioning

confidence: 99%

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

et al. 2016

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“…Here, the apparent and averaged binding constant determined for the analyte 1-SBE-␤-CD complex is more than 20 times greater than with the neutral Me-␤-CD, around 1210 M −1 . This result can suggest a high contribution of electrostatic interactions in the complexation process between the sulfobutylether group of the CD and the cationic piperazine chain of 1 but this contribution would be only partially responsible of the interaction taking into account the results of Luppi et al [43]. Among the four CD, the SBE-␤-CD appears to be the more appropriate CD to complex the compound 1.…”

Section: Choice Of the Coatingmentioning

confidence: 87%

“…Due to the cationic character of 1 and so as to enhance the complexation, the complexing ability of the anionic SBE-␤-CD, the only anionic CD used in marketed pharmaceutical products [7], was evaluated. It is worth mentioning than a previous work of Luppi et al [43] about nanoparticles carrying cyclodextrins in order to load tacrine, has shown that SBE-␤-CD significantly increases the drug loading whereas ␤-CD and HP-␤-CD did not affect it. Here, the apparent and averaged binding constant determined for the analyte 1-SBE-␤-CD complex is more than 20 times greater than with the neutral Me-␤-CD, around 1210 M −1 .…”

Section: Choice Of the Coatingmentioning

confidence: 94%

Evaluation of three neutral capillary coatings for the determination of analyte-cyclodextrin binding constants by affinity capillary electrophoresis. Application to N , N ⿲-disubstituted piperazine derivatives.

Danel

Melnyk

Azaroual

et al. 2016

Journal of Chromatography A

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The performances of three neutral static coatings (hydroxypropyl cellulose, polyethylene oxide and poly(N,N-dimethylacrylamide) have been evaluated in order to determine the binding constants of the complexes formed between four polycationic compounds (piperazine derivatives) and four cyclodextrins of pharmaceutical interest (β-CD, HP-β-CD, Me-β-CD and sulfobutyl ether-β-CD) by affinity capillary electrophoresis. The physically-adsorbed poly(N,N-dimethylacrylamide) coating proves to be the more efficient to mask the silanol groups of the capillary wall since the lowest electroosmotic flow was measured for this coating. Moreover, it drastically reduces the adsorption of the compounds since it allows a correct repeatability of their migration time, higher efficiencies of the peaks and no baseline shift. Then, it was verified for four complexes that this coating allows a correct determination of the binding constants avoiding the CD adsorption which is responsible of an undervaluation of binding constants. The highest binding constants are obtained using the anionic sulfobutyl ether-β-CD (SBE-β-CD). The structure of the complex formed between the tacrine derivative and the SBE-β-CD was further investigated through 2D ROESY NMR experiments and structure-binding constant relationships. Results suggest that the inclusion in the SBE-β-CD cavity occurs through the aliphatic ring portion of the tacrine moiety.

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“…NP carrying cyclodextrins showed mucoadhesion in vitro and ex-vivo and in particular HP-β cyclodextrin showed the highest mucoadhesive properties. Intranasal absorption studies in AD animal models are now needed to further validate this strategy [286].…”

Section: E) Nanoparticles For Cholinesterase Inhibitorsmentioning

confidence: 99%

Diagnostic and Therapeutic Uses of Nanomaterials in the Brain

Garbayo¹,

Mendoza²,

Blanco-Prieto

2014

CMC

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Nanomedicine has recently emerged as an exciting tool able to improve the early diagnosis and treatment of a variety of intractable or age-related brain disorders. The most relevant properties of nanomaterials are that they can be engineered in such a way that they can cross the blood brain barrier, with the final aim of targeting specific cells and molecules and to act as vehicles for drugs. Potentially beneficial properties of nanotherapeutics derived from its unique characteristics include improved efficacy, safety, sensitivity and personalization compared to conventional medicines.In this review, recent advances in available nanostructures and nanomaterials for brain applications will be described. Then, the latest nanotechnological applications for the treatment and diagnosis of neurological disorders, mainly brain tumors and neurodegenerative diseases, will be reviewed. Recent investigations of the neurotoxicity of the nanomaterial both in vitro and in vivo will be summarized. Finally, the ongoing challenges that have to be meet if new nanomedical products are to be put on the market will be discussed and some future directions will be outlined.

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Albumin nanoparticles carrying cyclodextrins for nasal delivery of the anti-Alzheimer drug tacrine

Cited by 114 publications

References 25 publications

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

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

Evaluation of three neutral capillary coatings for the determination of analyte-cyclodextrin binding constants by affinity capillary electrophoresis. Application to N , N ⿲-disubstituted piperazine derivatives.

Diagnostic and Therapeutic Uses of Nanomaterials in the Brain

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