2-Hydroxypropyl-β-cyclodextrins and the Blood-Brain Barrier: Considerations for Niemann-Pick Disease Type C1

Calias, Pericles

doi:10.2174/1381612823666171019164220

Cited by 31 publications

(25 citation statements)

References 33 publications

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“…The addition of cyclodextrin to chitosan carriers has the potential to enhance the pharmacokinetics, pharmacodynamics, stability, and brain uptake of the formulation. Similar research reports indicated the aforementioned properties when cyclodextrin are employed in drug delivery systems [108,109].…”

Section: Emulsionssupporting

confidence: 73%

Chitosan-Based Nanocarriers for Nose to Brain Delivery

Aderibigbe

Naki

2019

Applied Sciences

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In the treatment of brain diseases, most potent drugs that have been developed exhibit poor therapeutic outcomes resulting from the inability of a therapeutic amount of the drug to reach the brain. These drugs do not exhibit targeted drug delivery mechanisms, resulting in a high concentration of the drugs in vital organs leading to drug toxicity. Chitosan (CS) is a natural-based polymer. It has unique properties such as good biodegradability, biocompatibility, mucoadhesive properties, and it has been approved for biomedical applications. It has been used to develop nanocarriers for brain targeting via intranasal administration. Nanocarriers such as nanoparticles, in situ gels, nanoemulsions, and liposomes have been developed. In vitro and in vivo studies revealed that these nanocarriers exhibited enhanced drug uptake to the brain with reduced side effects resulting from the prolonged contact time of the nanocarriers with the nasal mucosa, the surface charge of the nanocarriers, the nano size of the nanocarriers, and their capability to stretch the tight junctions within the nasal mucosa. The aforementioned unique properties make chitosan a potential material for the development of nanocarriers for targeted drug delivery to the brain. This review will focus on chitosan-based carriers for brain targeting.

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Section: Emulsionssupporting

confidence: 73%

Chitosan-Based Nanocarriers for Nose to Brain Delivery

Aderibigbe

Naki

2019

Applied Sciences

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“…HPβCD is more effective in reversing NPC symptoms in the NPC1 KO mice when delivered directly to the brain because HPβCD does not effectively cross the blood-brain barrier (BBB) [ 6 ]. For example, a 23 mg/kg HPβCD intracerebroventricular injection has a better outcome than a 4000 mg/kg HPβCD subcutaneous injection [ 1 ].…”

Section: Resultsmentioning

confidence: 99%

The susceptibility of cochlear outer hair cells to cyclodextrin is not related to their electromotile activity

Zhou

Takahashi

Homma

et al. 2018

acta neuropathol commun

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Niemann-Pick Type C1 (NPC1) disease is a fatal neurovisceral disorder caused by dysfunction of NPC1 protein, which plays a role in intracellular cholesterol trafficking. The cholesterol-chelating agent, 2-hydroxypropyl-β-cyclodextrin (HPβCD), is currently undergoing clinical trials for treatment of this disease. Though promising in alleviating neurological symptoms, HPβCD causes irreversible hearing loss in NPC1 patients and outer hair cell (OHC) death in animal models. We recently found that HPβCD-induced OHC death can be significantly alleviated in a mouse model lacking prestin, an OHC-specific motor protein required for the high sensitivity and sharp frequency selectivity of mammalian hearing. Since cholesterol status is known to influence prestin’s electromotility, we examined how prestin contributes to HPβCD-induced OHC death in the disease context using the NPC1 knockout (KO) mouse model (NPC1-KO). We found normal expression and localization of prestin in NPC1-KO OHCs. Whole-cell patch-clamp recordings revealed a significant depolarization of the voltage-operating point of prestin in NPC1-KO mice, suggesting reduced levels of cholesterol in the lateral membrane of OHCs that lack NPC1. OHC loss and elevated thresholds were found for high frequency regions in NPC1-KO mice, whose OHCs retained their sensitivity to HPβCD. To investigate whether prestin’s electromotile function contributes to HPβCD-induced OHC death, the prestin inhibitor salicylate was co-administered with HPβCD to WT and NPC1-KO mice. Neither oral nor intraperitoneal administration of salicylate mitigated HPβCD-induced OHC loss. To further determine the contribution of prestin’s electromotile function, a mouse model expressing a virtually nonelectromotile prestin protein (499-prestin) was subjected to HPβCD treatment. 499-prestin knockin mice showed no resistance to HPβCD-induced OHC loss. As 499-prestin maintains its ability to bind cholesterol, our data imply that HPβCD-induced OHC death is ascribed to the structural role of prestin in maintaining the OHC’s lateral membrane, rather than its motor function.Electronic supplementary materialThe online version of this article (10.1186/s40478-018-0599-9) contains supplementary material, which is available to authorized users.

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“…However, the principal difficulty of treatment with CD is the molecule’s inability to cross the blood–brain barrier, and while subcutaneous injection can decrease the level of cholesterol in several tissues, an intrathecal injection is needed to have any effect in the brain [ 48 , 49 ]. Indeed, intrathecal injections prevent some adverse effect of CD treatment such as lung toxicity.…”

Section: Cyclodextrins As Active Drugsmentioning

confidence: 99%

Cyclic Oligosaccharides as Active Drugs, an Updated Review

et al. 2020

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There have been many reviews of the cyclic oligosaccharide cyclodextrin (CD) and CD-based materials used for drug delivery, but the capacity of CDs to complex different agents and their own intrinsic properties suggest they might also be considered for use as active drugs, not only as carriers. The aim of this review is to summarize the direct use of CDs as drugs, without using its complexing potential with other substances. The direct application of another oligosaccharide called cyclic nigerosyl-1,6-nigerose (CNN) is also described. The review is divided into lipid-related diseases, aggregation diseases, antiviral and antiparasitic activities, anti-anesthetic agent, function in diet, removal of organic toxins, CDs and collagen, cell differentiation, and finally, their use in contact lenses in which no drug other than CDs are involved. In the case of CNN, its application as a dietary supplement and immunological modulator is explained. Finally, a critical structure–activity explanation is provided.

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2-Hydroxypropyl-β-cyclodextrins and the Blood-Brain Barrier: Considerations for Niemann-Pick Disease Type C1

Cited by 31 publications

References 33 publications

Chitosan-Based Nanocarriers for Nose to Brain Delivery

Chitosan-Based Nanocarriers for Nose to Brain Delivery

The susceptibility of cochlear outer hair cells to cyclodextrin is not related to their electromotile activity

Cyclic Oligosaccharides as Active Drugs, an Updated Review

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