Sulfobutylether-β-cyclodextrin: A functional biopolymer for drug delivery applications

Pardeshi, Chandrakantsing V.; Kothawade, Rucha V.; Markad, Ashwini R.; Pardeshi, Sagar R.; Kulkarni, Abhijeet D.; Chaudhari, Prashant; Longhi, Marcela Raquel; Dhas, Namdev; Naik, Jitendra; Surana, Sanjay J.; Garcia, Monica C.

doi:10.1016/j.carbpol.2022.120347

Cited by 34 publications

(13 citation statements)

References 103 publications

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“…SBECD was selected as an optimal carrier as a widely known, parenterally safe cyclodextrin derivative with excellent solubilization properties and polyanionic nature [33][34][35], CHR was successfully solubilized with SBECD earlier [5] while the interaction between SBECD and OTX008…”

Section: Discussionmentioning

confidence: 99%

“…However, this approach requires an appropriate delivery system to facilitate their combined solubilization and delivery. SBECD was chosen as the preferred carrier due to its established safety for parenteral use, superior solubilizing capabilities, and polyanionic character [22][23][24]. Previous research has demonstrated the successful solubilization of CHR using SBECD [5].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Chrysin directing an enhanced solubility through the formation of a supramolecular cyclodextrin-calixarene drug delivery system: a potential strategy in antifibrotic diabetes therapeutics

Hermenean,

Dossi,

Hamilton

et al. 2023

Preprint

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BackgroundCalixarene OTX008 and chrysin (CHR) are promising molecules for the treatment of fibrosis and diabetes complications, however, a suitable drug delivery system is required for their combined application due to their low solubility and bioavailability.Research design and methodsSulfobutylated β-cyclodextrin (SBECD) and its polymeric derivative were tested to solubilize CHR through the formation of a ternary complex in presence of calixarene OTX008. Phase-solubility studies revealed the solubility enhancement and complexation mechanisms, and dynamic light-scattering was used to measure the molecular association in the cyclodextrin-calixarene-CHR ternary system. Nuclear magnetic resonance, differential scanning calorimetry, and computational studies discovered the molecular interactions in the complex, while cellular studies tested the biocompatibility of the system.ResultsUsing SBECD and OTX008 together proved more efficient in solubilizing CHR than using SBECD by itself. The ternary complex forms molecular associates in water, which contributes to the solubilization and delivery of both CHR and OTX008. Structural analysis identified non-covalent interactions involved in the formation of the complex, which was not cytotoxic in vitro under hyperglycemic conditions.ConclusionsA novel ternary complex was developed for administering potential antifibrotic compounds in diabetes complications, with OTX008 serving as a pivotal structural and pharmacological element within the complex.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Chrysin directing an enhanced solubility through the formation of a supramolecular cyclodextrin-calixarene drug delivery system: a potential strategy in antifibrotic diabetes therapeutics

Hermenean,

Dossi,

Hamilton

et al. 2023

Preprint

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“…40 Ganaxolone is formulated with sulfobutylether-β-cyclodextrin, a commonly used excipient with well-established safety in humans, to optimize solubility and stability. 31,41 Ganaxolone received orphan drug designation for the treatment of various seizure disorders, including infantile spasms (1994), protocadherin 19 female epilepsy (2015), status epilepticus (2016), fragile X syndrome (2016), CDD (2017), tuberous sclerosis complex (2021), and Lennox-Gastaut syndrome (2023) to support the compound's ongoing clinical development. In this study of healthy volunteers, subjects maintained a baseline level of alertness with mean plasma concentrations up to 1240 ng/mL.…”

Section: Discussionmentioning

confidence: 99%

“…A commercial formulation of alphaxolone and alphadolone was briefly available but withdrawn from the market in the 1970s due to toxicity associated with the product's excipient, cremophor, although it remains available for veterinary use 40 . Ganaxolone is formulated with sulfobutylether‐β‐cyclodextrin, a commonly used excipient with well‐established safety in humans, to optimize solubility and stability 31,41 . Ganaxolone received orphan drug designation for the treatment of various seizure disorders, including infantile spasms (1994), protocadherin 19 female epilepsy (2015), status epilepticus (2016), fragile X syndrome (2016), CDD (2017), tuberous sclerosis complex (2021), and Lennox–Gastaut syndrome (2023) to support the compound's ongoing clinical development.…”

Section: Discussionmentioning

confidence: 99%

Intravenous Ganaxolone: Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability in Healthy Adults

Gasior,

Husain,

Barra

et al. 2024

Clinical Pharm in Drug Dev

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Ganaxolone, a neuroactive steroid anticonvulsant that modulates both synaptic and extrasynaptic γ‐aminobutyric acid type A (GABAA) receptors, is in development for treatment of status epilepticus (SE) and rare epileptic disorders, and has been approved in the United States for treatment of seizures associated with cyclin‐dependent kinase‐like 5 deficiency disorder in patients ≥2 years old. This phase 1 study in 36 healthy volunteers evaluated the pharmacokinetics, pharmacodynamics, and safety of intravenous ganaxolone administered as a (i) single bolus, (ii) infusion, and (iii) bolus followed by continuous infusion. After a single bolus over 2 minutes (20 mg) or 5 minutes (10 or 30 mg), ganaxolone was detected in plasma with a median Tmax of 5 minutes, whereas a 60‐minute infusion (10 or 30 mg) or a bolus (6 mg over 5 minutes) followed by infusion (20 mg/h) for 4 hours achieved a median Tmax of approximately 1 and 3 hours, respectively. Cmax was dose and administration‐time dependent, ranging from 73.8 ng/mL (10 mg over 5 minutes) to 1240 ng/mL (30 mg over 5 minutes). Bolus doses above 10 mg of ganaxolone markedly influenced the bispectral index score with a rapid decline; smaller changes occurred on the Modified Observer's Assessment of Alertness/Sedation scale and in quantitative electroencephalogram. Most adverse events were of mild severity, with 2 events of moderate severity; none were reported as serious. No effects on systemic hemodynamics or respiratory functions were reported. Overall, ganaxolone was generally well tolerated at the doses studied and demonstrated pharmacokinetic and pharmacodynamic properties suitable to treat SE.

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“…SBE-β-CD has provided a smart solution to the commercial development of many therapeutics by overcoming the major hurdles of the poor solubility and instability of pharmacologically active candidates, such as TQ [ 11 ]. However, the estimation of CDs (including SBE-β-CD) in different biological media must be investigated via stringent pharmacokinetic [ 12 ] and toxicological studies of SBE-β-CD-enabled drug formulations [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

Characterization of Thymoquinone-Sulfobutylether-β-Cyclodextrin Inclusion Complex for Anticancer Applications

et al. 2023

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Thymoquinone (TQ) is a quinone derived from the black seed Nigella sativa and has been extensively studied in pharmaceutical and nutraceutical research due to its therapeutic potential and pharmacological properties. Although the chemopreventive and potential anticancer effects of TQ have been reported, its limited solubility and poor delivery remain the major limitations. In this study, we aimed to characterize the inclusion complexes of TQ with Sulfobutylether-β-cyclodextrin (SBE-β-CD) at four different temperatures (293–318 K). Additionally, we compared the antiproliferative activity of TQ alone to TQ complexed with SBE-β-CD on six different cancer cell lines, including colon, breast, and liver cancer cells (HCT-116, HT-29, MDA-MB-231, MCF-7, SK-BR-3, and HepG2), using an MTT assay. We calculated the thermodynamic parameters (ΔH, ΔS, and ΔG) using the van’t Holf equation. The inclusion complexes were characterized by X-ray diffraction (XRD), Fourier transforms infrared (FT-IR), and molecular dynamics using the PM6 model. Our findings revealed that the solubility of TQ was improved by ≥60 folds, allowing TQ to penetrate completely into the cavity of SBE-β-CD. The IC50 values of TQ/SBE-β-CD ranged from 0.1 ± 0.01 µg/mL against SK-BR-3 human breast cancer cells to 1.2 ± 0.16 µg/mL against HCT-116 human colorectal cancer cells, depending on the cell line. In comparison, the IC50 values of TQ alone ranged from 0.2 ± 0.01 µg/mL to 4.7 ± 0.21 µg/mL. Overall, our results suggest that SBE-β-CD can enhance the anticancer effect of TQ by increasing its solubility and bioavailability and cellular uptake. However, further studies are necessary to fully understand the underlying mechanisms and potential side effects of using SBE-β-CD as a drug delivery system for TQ.

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Sulfobutylether-β-cyclodextrin: A functional biopolymer for drug delivery applications

Cited by 34 publications

References 103 publications

Chrysin directing an enhanced solubility through the formation of a supramolecular cyclodextrin-calixarene drug delivery system: a potential strategy in antifibrotic diabetes therapeutics

Chrysin directing an enhanced solubility through the formation of a supramolecular cyclodextrin-calixarene drug delivery system: a potential strategy in antifibrotic diabetes therapeutics

Intravenous Ganaxolone: Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability in Healthy Adults

Characterization of Thymoquinone-Sulfobutylether-β-Cyclodextrin Inclusion Complex for Anticancer Applications

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