Enhanced delivery of daidzein into fibroblasts and neuronal cells with cationic derivatives of gamma-cyclodextrin for the control of cellular glycosaminoglycans

Kamiński, Kamil; Kujdowicz, Monika; Kajta, Małgorzata; Nowakowska, Maria; Szczubiałka, Krzysztof

doi:10.1016/j.ejpb.2015.02.002

Cited by 11 publications

(8 citation statements)

References 47 publications

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“…As a delivery vehicle for DAI, we used a cationic derivative of γ-cyclodextrin (GCD) synthesized by substitution with ethylenediamine (EDA), as described previously [50]. We previously successfully used the GCD-EDA/DAI complex to deliver DAI to murine neuronal cells and human fibroblasts [50].…”

Section: Resultsmentioning

confidence: 99%

“…We found that the complex easily penetrated human fibroblasts and murine hippocampal neuronal cells [50]. Moreover, we found that DAI delivered in the form of GCD-EDA/DAI complex decreased the total GAG levels in normal human dermal fibroblasts [50]. These encouraging results prompted us to extend our studies on the delivery of DAI by applying the above complex to an in vivo rat model.…”

Section: Introductionmentioning

confidence: 81%

“…In our previous studies, we obtained ethylenediamine-modified γ-cyclodextrin (GCD-EDA) and its inclusion complex with DAI (GCD-EDA/DAI). We found that the complex easily penetrated human fibroblasts and murine hippocampal neuronal cells [50]. Moreover, we found that DAI delivered in the form of GCD-EDA/DAI complex decreased the total GAG levels in normal human dermal fibroblasts [50].…”

Section: Introductionmentioning

confidence: 86%

“…Daidzein (>98% purity), genistein used as an internal standard (IS) (>98% purity), formic acid of LC/MS purity, and PBS buffer (pH = 7.4) were purchased from Sigma-Aldrich (St. Louis, MO, USA). Methanol and acetonitrile of HPLC purity were supplied by Merck (Darmstadt, Germany) and ethylenediamine (EDA)-modified γ-cyclodextrin complex with daidzein (GCD-EDA/DAI) was synthesized as previously described [50]. The DAI content in the complex was 2.7%.…”

Section: Methodsmentioning

confidence: 99%

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Improved Pharmacokinetics and Tissue Uptake of Complexed Daidzein in Rats

et al. 2020

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The pharmacokinetic profile and tissue uptake of daidzein (DAI) was determined in rat serum and tissues (lungs, eyes, brain, heart, spleen, fat, liver, kidney, and testes) after intravenous and intraperitoneal administration of DAI in suspension or complexed with ethylenediamine-modified γ-cyclodextrin (GCD-EDA/DAI). The absolute and relative bioavailability of DAI suspended (20 mg/kg i.v. vs. 50 mg/kg i.p.) and complexed (0.54 mg/kg i.v. vs. 1.35 mg/kg i.p.) was determined. After i.p. administration, absorption of DAI complexed with GCD-EDA was more rapid (tmax = 15 min) than that of DAI in suspension (tmax = 45 min) with a ca. 3.6 times higher maximum concentration (Cmax = 615 vs. 173 ng/mL). The i.v. half-life of DAI was longer in GCD-EDA/DAI complex compared with DAI in suspension (t0.5 = 380 min vs. 230 min). The volume of distribution of DAI given i.v. in GCD-EDA/DAI complex was ca. 6 times larger than DAI in suspension (38.6 L/kg vs. 6.2 L/kg). Our data support the concept that the pharmacokinetics of DAI suspended in high doses are nonlinear. Increasing the intravenous dose 34 times resulted in a 5-fold increase in AUC. In turn, increasing the intraperitoneal dose 37 times resulted in a ca. 2-fold increase in AUC. The results of this study suggested that GCD-EDA complex may improve DAI bioavailability after i.p. administration. The absolute bioavailability of DAI in GCD-EDA inclusion complex was ca. 3 times greater (F = 82.4% vs. 28.2%), and the relative bioavailability was ca. 21 times higher than that of DAI in suspension, indicating the need to study DAI bioavailability after administration by routes other than intraperitoneal, e.g., orally, subcutaneously, or intramuscularly. The concentration of DAI released from GCD-EDA/DAI inclusion complex to all the rat tissues studied was higher than after administration of DAI in suspension. The concentration of DAI in brain and lungs was found to be almost 90 and 45 times higher, respectively, when administered in complex compared to the suspended DAI. Given the nonlinear relationship between DAI bioavailability and the dose released from the GCD-EDA complex, complexation of DAI may thus offer an effective approach to improve DAI delivery for treatment purposes, for example in mucopolysaccharidosis (MPS), allowing the reduction of ingested DAI doses.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 81%

Section: Introductionmentioning

confidence: 86%

Section: Methodsmentioning

confidence: 99%

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Improved Pharmacokinetics and Tissue Uptake of Complexed Daidzein in Rats

et al. 2020

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“…NR is a fluorescent solvatochromic dye, which emits strongly in hydrophobic environments and is quenched in aqueous solutions . It was previously reported that native β‐CD can form an inclusion complex NR with a 1:1 stoichiometry . Inclusion complex formation results in a significant increase in both the fluorescence quantum yield and the fluorescence lifetime of NR, and a blueshift in its fluorescence emission relative to that in water.…”

Section: Resultsmentioning

confidence: 99%

Highly Functionalized β‐Cyclodextrins by Solid‐Supported Synthesis

Vurgun

Nitz

2018

Chemistry A European J

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Using covalent capture, a high yielding selective mono-functionalization of heptakis-[6-deoxy-6-(2-aminoethylsulfanyl)]-β-CD with a 5-mercaptopentyl functional group has been achieved. Here, we demonstrate the immobilization of the mono-thiol functionalized β-CD on PEGA resin via a disulfide bond, enabling solid-phase elaboration of the remaining six primary amines. To showcase the potential of this method, the amines were elaborated to tripeptides through standard Fmoc-peptide chemistry. A small library of CD-tripeptide conjugates was generated which, when reduced from the solid support, could be tagged at the released thiol with an environmentally sensitive fluorophore. The resulting library of sensors showed potential for the differential sensing of various bile salts. The described methodology provides a rapid and versatile route to synthesize highly functionalized libraries of CD derivatives that may be tailored towards applications in sensing, catalysis, and multivalent displays.

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