Cyclodextrins applied to the treatment of lysosomal storage disorders

Ishitsuka, Yoichi; Irie, Tetsumi; Matsuo, Muneaki

doi:10.1016/j.addr.2022.114617

Cited by 21 publications

(9 citation statements)

References 161 publications

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“…Interestingly, preclinical and clinical data suggest that HP-β-CD can be used as an active pharmaceutical ingredient in the treatment of various neurological diseases, 65 such as inhibition of intracellular cholesterol accumulation through plasma membrane interactions, which plays a beneficial role in Niemann-Pick type C disease, 20,66 and the promising neuroprotective effect in Alzheimer's disease by cholesterol transport and Aβ clearance. 21,67 While previous research has shown the neuroprotective effects of HP-β-CD in MPTP-induced PD mouse models by increasing the autophagy, 22 further independent controlled trials are required to verify the neuroprotective effects of HP-β-CD in PD animal models. Moreover, whether HP-β-CD plays a neuroprotective role by regulating the composition and metabolism of intestinal microbiota is also a question worth exploring in the future.…”

Section: Discussionmentioning

confidence: 99%

Integrated multi-omics profiling highlights the benefits of resveratrol hydroxypropyl-β-cyclodextrin inclusion complex for A53T transgenic mice through the microbiota–gut–brain axis

Sun,

Feng,

Qin

et al. 2024

Food Funct.

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Section: Discussionmentioning

confidence: 99%

Integrated multi-omics profiling highlights the benefits of resveratrol hydroxypropyl-β-cyclodextrin inclusion complex for A53T transgenic mice through the microbiota–gut–brain axis

Sun,

Feng,

Qin

et al. 2024

Food Funct.

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“…A study has shown that supramolecular therapeutics are powerful candidates to treat macular disease by removing toxic metabolites from host-guest inclusions [ 57 ]. Matsuo et al also demonstrated that HP-β-CyD has been useful for clinical Niemann-Pick disease type C treatment [ 58 ].…”

Section: Applicationmentioning

confidence: 99%

The Role of Cyclodextrin in the Construction of Nanoplatforms: From Structure, Function and Application Perspectives

et al. 2023

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Cyclodextrins (CyDs) in nano drug delivery systems have received much attention in pursuit of good compatibility, negligible toxicity, and improved pharmacokinetics of drugs. Their unique internal cavity has widened the application of CyDs in drug delivery based on its advantages. Besides this, the polyhydroxy structure has further extended the functions of CyDs by inter- and intramolecular interactions and chemical modification. Furthermore, the versatile functions of the complex contribute to alteration of the physicochemical characteristics of the drugs, significant therapeutic promise, a stimulus-responsive switch, a self-assembly capability, and fiber formation. This review attempts to list recent interesting strategies regarding CyDs and discusses their roles in nanoplatforms, and may act as a guideline for developing novel nanoplatforms. Future perspectives on the construction of CyD-based nanoplatforms are also discussed at the end of this review, which may provide possible direction for the construction of more rational and cost-effective delivery vehicles.

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“…Cyclodextrins (CDs), cyclic oligosaccharides consisting of six, seven and eight D‐glucopyranose units, called α‐, β‐ and γ‐CDs, respectively, are considered the most promising therapeutic candidates for NPC 4,5 . Their unique cyclic structure, featuring a hydrophilic outer surface and a hydrophobic inner cavity, provides the ability to form water‐soluble inclusion complexes with guest molecules of an appropriate size and low polarity, such as UC 6,7 .…”

Section: Introductionmentioning

confidence: 99%

“…3 Cyclodextrins (CDs), cyclic oligosaccharides consisting of six, seven and eight D-glucopyranose units, called α-, β-and γ-CDs, respectively, are considered the most promising therapeutic candidates for NPC. 4,5 Their unique cyclic structure, featuring a hydrophilic outer surface and a hydrophobic inner cavity, provides the ability to form water-soluble inclusion complexes with guest molecules of an appropriate size and low polarity, such as UC. 6,7 We and other groups previously suggested that CDs serve dual functions of UC "shuttle" and "sink", whereby they enhance the bidirectional flux of UC, without changing the equilibrium UC distribution between the plasma membrane and vesicles at lower concentrations while facilitating UC efflux from the plasma membrane and serving themselves as extracellular UC reservoirs at higher concentrations.…”

Section: Introductionmentioning

confidence: 99%

Different solubilizing ability of cyclodextrin derivatives for cholesterol in Niemann–Pick disease type C treatment

Yamada,

Fukaura‐Nishizawa,

Nishiyama

et al. 2023

Clinical & Translational Med

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BackgroundNiemann–Pick disease type C (NPC) is a fatal neurodegenerative disorder caused by abnormal intracellular cholesterol trafficking. Cyclodextrins (CDs), the most promising therapeutic candidates for NPC, but with concerns about ototoxicity, are cyclic oligosaccharides with dual functions of unesterified cholesterol (UC) shuttle and sink that catalytically enhance the bidirectional flux and net efflux of UC, respectively, between the cell membrane and the extracellular acceptors. However, the properties of CDs that regulate these functions and how they could be used to improve treatments for NPC are unclear.MethodsWe estimated CD–UC complexation for nine CD derivatives derived from native α‐, β‐, and γ‐CD with different cavity sizes, using solubility and molecular docking analyses. The stoichiometry and complexation ability of the resulting complexes were investigated in relation to the therapeutic effectiveness and toxicity of each CD derivative in NPC experimental models.FindingsWe found that shuttle and sink activities of CDs are dependent on cavity size‐dependent stoichiometry and substituent‐associated stability of CD–UC complexation. The ability of CD derivatives to form 1:1 and 2:1 complexes with UC were correlated with their ability to normalize intracellular cholesterol trafficking serving as shuttle and with their cytotoxicity associated with cellular UC efflux acting as sink, respectively, in NPC model cells. Notably, the ability of CD derivatives to form an inclusion complex with UC was responsible for not only efficacy but ototoxicity, while a representative derivative without this ability negligibly affected auditory function, underscoring its preventability.ConclusionsOur findings highlight the importance of strategies for optimizing the molecular structure of CDs to overcome this functional dilemma in the treatment of NPC.

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Cyclodextrins applied to the treatment of lysosomal storage disorders

Cited by 21 publications

References 161 publications

Integrated multi-omics profiling highlights the benefits of resveratrol hydroxypropyl-β-cyclodextrin inclusion complex for A53T transgenic mice through the microbiota–gut–brain axis

Integrated multi-omics profiling highlights the benefits of resveratrol hydroxypropyl-β-cyclodextrin inclusion complex for A53T transgenic mice through the microbiota–gut–brain axis

The Role of Cyclodextrin in the Construction of Nanoplatforms: From Structure, Function and Application Perspectives

Different solubilizing ability of cyclodextrin derivatives for cholesterol in Niemann–Pick disease type C treatment

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