Controlling the binding of hydrophobic drugs with supramolecular assemblies of β-cyclodextrin

Kashapov, Ruslan R.; Мамедов, В. А.; Zhukova, Nataliya; Kadirov, Marsil K.; Nizameev, Irek R.; Zakharova, L. Ya.; Sinyashin, Оleg G.

doi:10.1016/j.colsurfa.2017.05.026

Cited by 17 publications

(8 citation statements)

References 51 publications

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“…Cyclodextrins (CDs) are FDA-approved cyclic oligosaccharides with a hydrophilic outer surface and internal hydrophobic cavity that can form inclusion complexes with many hydrophobic molecules 12,13. It has been proven that inclusion complexes of CDs have the potential to increase the apparent solubility and bioavailability of many drugs 14–16. Among natural CDs, βCD (Figure 1B) is the most popular, because of its suitable cavity size for trapping many hydrophobic molecules 14.…”

Section: Introductionmentioning

confidence: 99%

“…It has been proven that inclusion complexes of CDs have the potential to increase the apparent solubility and bioavailability of many drugs 14–16. Among natural CDs, βCD (Figure 1B) is the most popular, because of its suitable cavity size for trapping many hydrophobic molecules 14. Inclusion-complex formation with hydrophobic molecules not only increases their apparent solubility with reduced use of toxic solvents but also leads to sustained release of hydrophobic molecules with no burst effect.…”

Section: Introductionmentioning

confidence: 99%

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<p>Enhanced Cellular Uptake Of Phenamil Through Inclusion Complex With Histidine Functionalized β-Cyclodextrin As Penetrative Osteoinductive Agent</p>

Jahed¹,

Vasheghani‐Farahani²,

Bagheri³

et al. 2019

IJN

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BackgroundPhenamil (PH) is a small molecule that induces bone formation through upregulation of the TRB3 gene in the bone-regeneration process. β-Cyclodextrins (βCDs) with hydrophilic surfaces and a relatively hydrophobic cavity can form inclusion complexes with primarily hydrophobic small molecules such as PH, and increase their apparent solubility and dissolution rate. The hydrophilic surface of βCDs prevents their interaction with the hydrophobic lipids of the cell membrane for penetration. Therefore, binding of penetrative groups, such as lysine, arginine, and histidine (His), to βCDs for cell penetration is required.AimThe aim of this study was to investigate the effect of His-conjugated βCD on cellular uptake of PH for bone differentiation.MethodsIn this study, His-βCDs were synthesized and used to prepare an inclusion complex of His-βCD-PH. A hydroxypropyl–βCD-PH (HP-βCD-PH) inclusion complex for increasing PH solubility without a penetrative group was prepared for comparison. 3-D geometry of βCD derivatives and PH-inclusion complexes was investigated by Fourier-transform infrared spectroscopy and molecular docking. Alizarin red staining and real-time PCR were performed to compare bone differentiation of His-βCD-PH and HP-βCD-PH.ResultsThe results suggested that the benzene ring of PH was inserted into the wide side of both His-βCD and HP-βCD. Alizarin red staining at 14 days postculture in the presence of His-βCD-PH at total concentration of 50 μM for PH showed that bone-matrix mineralization increased significantly compared with free PH and HP-βCD-PH. Real-time PCR confirmed this result, and showed gene expression increased significantly (OPN 1.84-fold, OCN 1.69-fold) when stem cells were cultured with His-βCD-PH.ConclusionThe overall results indicated that His-βCD-PH is a promising carrier for osteoinductive PH with possible penetration ability and sustained release that reduces BMP2 consumption for differentiation of mesenchymal stem cells to bone tissue.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

<p>Enhanced Cellular Uptake Of Phenamil Through Inclusion Complex With Histidine Functionalized β-Cyclodextrin As Penetrative Osteoinductive Agent</p>

Jahed¹,

Vasheghani‐Farahani²,

Bagheri³

et al. 2019

IJN

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“…Interestingly, the inclusion complexes aggregations in aqueous solutions typically result in large micelle-like structures [ 22 ], micrometer-sized rods [ 20 , 38 , 39 ], or spherical shape nanoaggregates [ 15 ], while the formation of wires is more distinctive to unmodified cyclodextrins [ 21 ].…”

Section: Resultsmentioning

confidence: 99%

Cyclodextrin Encapsulated pH Sensitive Dyes as Fluorescent Cellular Probes: Self-Aggregation and In Vitro Assessments

et al. 2020

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We have designed and synthesized a series of novel, supramolecular, long-lived fluorescent probes based on the host-guest inclusion complexes formation between fluorescent indolizinyl-pyridinium salts and β-cyclodextrin. Fluorescence and electrospray ionisation mass spectrometry experiments, supported by theoretical molecular docking studies, were utilized in the monitoring of the inclusion complexes formation, evidencing the appearance of corresponding 1:1 and 1:2 species. Additionally, the influence of the guest molecule over the aggregation processes of the cyclodextrin inclusion complexes was investigated by transmission electron microscopy. The absence of cytotoxicity, cellular permeability, long-lived intracellular fluorescence, and in time specific accumulation within acidic organelles identified the investigated supramolecular entities as remarkable candidates for intracellular fluorescence probes. Co-staining experiments using specific organelle markers revealed the fact that, after a 24-h incubation period, the inclusion complexes accumulate predominantly in lysosomes rather than in mitochondria. This study opens new possibilities for a broad range of fluorescent dyes with solubility and high toxicity issues, able to form inclusion complexes with β-cyclodextrin, to be tested as intracellular fluorescence probes.

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“…The cationic surfactant, cetyltrimethylammonium bromide, was then used as a competitive binding trigger to disrupt these aggregates and release the bound drug. The study also modified this same drug which resulted in higher binding affinity to β-CD and made the aggregates less sensitive to the surfactant, thus requiring higher concentrations to release comparable amounts of drug 155. Other work has designed vesicles for drug delivery that rely on competitive guest binding to release encapsulated drugs.…”

Section: Integrating Stimuli-responsive Function In the Applicatiomentioning

confidence: 99%

Integrating Stimuli-Responsive Properties in Host-Guest Supramolecular Drug Delivery Systems

2019

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Host-guest motifs are likely the most recognizable manifestation of supramolecular chemistry. These complexes are characterized by the organization of small molecules on the basis of preferential association of a guest within the portal of a host. In the context of their therapeutic use, the primary application of these complexes has been as excipients which enhance the solubility or improve the stability of drug formulations, primarily in a vial. However, there may be opportunities to go significantly beyond such a role and leverage key features of the affinity, specificity, and dynamics of the interaction itself toward “smarter” therapeutic designs. One approach in this regard would seek stimuli-responsive host-guest recognition, wherein a complex forms in a manner that is sensitive to, or can be governed by, externally applied triggers, disease-specific proteins and analytes, or the presence of a competing guest. This review will highlight the general and phenomenological design considerations governing host-guest recognition and the specific types of chemistry which have been used and are available for different applications. Finally, a discussion of the molecular engineering and design approaches which enable sensitivity to a variety of different stimuli are highlighted. Ultimately, these molecular-scale approaches offer an assortment of new chemistry and material design tools toward improving precision in drug delivery.

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Controlling the binding of hydrophobic drugs with supramolecular assemblies of β-cyclodextrin

Cited by 17 publications

References 51 publications

<p>Enhanced Cellular Uptake Of Phenamil Through Inclusion Complex With Histidine Functionalized β-Cyclodextrin As Penetrative Osteoinductive Agent</p>

<p>Enhanced Cellular Uptake Of Phenamil Through Inclusion Complex With Histidine Functionalized β-Cyclodextrin As Penetrative Osteoinductive Agent</p>

Cyclodextrin Encapsulated pH Sensitive Dyes as Fluorescent Cellular Probes: Self-Aggregation and In Vitro Assessments

Integrating Stimuli-Responsive Properties in Host-Guest Supramolecular Drug Delivery Systems

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