Cyclodextrins in Drug Delivery Systems and Their Effects on Biological Barriers

Haimhoffer, Ádám; Rusznyák, Ágnes; Réti-Nagy, Katalin; Vasvári, Gábor; Váradi, Judit; Vecsernyés, Miklós; Bácskay, Ildikó; Fehér, Pálma; Ujhelyi, Zoltán; Fenyvesi, Ferenc

doi:10.3390/scipharm87040033

Cited by 129 publications

(87 citation statements)

References 133 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…RAMEB is a lipophilic cyclodextrin derivative with several effects on cell membranes and monolayers, which can influence drug permeability. The solubility and permeability enhancement of drugs through the unstirred water layer (UWL) can be the major mechanisms, but cell membrane permeabilization, changes in the tight junctions (TJ), and endocytosis of the complexes could be also mentioned [26]. It was found earlier that the basolateral to apical flux of chrysin was about 2-fold higher than the apical to basolateral flux on Caco-2 monolayers.…”

Section: Discussionmentioning

confidence: 99%

Cyclodextrin Complexation Improves the Solubility and Caco-2 Permeability of Chrysin

et al. 2020

Self Cite

View full text Add to dashboard Cite

Chrysin is a bioflavonoid that can be found in natural products such as honey and propolis, and it possesses several biological effects such as antioxidant, anti-inflammatory, and anti-cancer activity. However, it is poorly soluble in water, and its bioavailability is limited. The aim of this research is to investigate the chrysin solubilization capacity of different β-cylcodextrin derivatives and compare their biological activities. Chrysin was complexed with β-cyclodextrin (βCD), hydroxypropyl-β-, (HPBCD) sulfobutylether-β-, (SBECD), and randomly-methylated-β-cyclodextrin (RAMEB) by the lyophilization method in 1:1 and 1:2 molar ratios. The solubilities of the chrysin–cyclodextrin complexes were tested, and the solubilization abilities of cyclodextrins were studied by phase solubility experiments. The cytotoxicity of the complexes was measured by the MTT method, and the permeability enhancement was tested on Caco-2 monolayers. The solubility study showed that the complexes formed with RAMEB had the highest solubility in water. The phase solubility experiments confirmed the strongest interaction between RAMEB and chrysin. In the viability test, none of the complexes showed cytotoxicity up to 100 µM concentration. The permeability study revealed that both at 1:1 and 1:2 ratios, the RAMEB complexes were the most effective to enhance chrysin permeability through the Caco-2 monolayers. In conclusion, cyclodextrins, especially RAMEB, are suitable for improving chrysin solubility and absorption.

show abstract

Section: Discussionmentioning

confidence: 99%

Cyclodextrin Complexation Improves the Solubility and Caco-2 Permeability of Chrysin

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…Among the class of β-cyclodextrin derivatives, (2-hydroxypropyl) beta-cyclodextrin (HP) is an approved pharmaceutical excipient and its monograph has been published in both the European Pharmacopoeia and United States Pharmacopoeia [5]. HP is recognized also as an active pharmaceutical ingredient and received the orphan drug designation for the treatment of Niemann-Pick disease from the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) [5][6][7][8]. Moreover, HP is able to provide protection against neurotoxicity induced by β-amyloid, and therefore useful in the treatment of Alzheimer's disease [8][9][10].…”

Section: Introductionmentioning

confidence: 99%

Investigation of Cytotoxicity and Cell Uptake of Cationic Beta-Cyclodextrins as Valid Tools in Nasal Delivery

et al. 2020

View full text Add to dashboard Cite

Cyclodextrin polymers have high applicability in pharmaceutical formulations due to better biocompatibility, solubility enhancement, loading capacity and controlled drug release than their parent, cyclodextrins. The cytotoxicity and cell uptake of new cationic beta-cyclodextrin monomers and polymers were evaluated as suitable materials for nasal formulations and their protective effects on cells exposed to hydrogen peroxide were studied. PC12 and CACO-2 cells were selected as the neuronal- and epithelial-type cells, respectively, to mimic the structure of respiratory and olfactory epithelia of the nasal cavity. All cationic beta-cyclodextrin polymers tested showed dose- and time-dependent toxicity; nevertheless, at 5 µM concentration and 60 min of exposure, the quaternary-ammonium-beta-cyclodextrin soluble polymer could be recognized as nontoxic. Based on these results, a fluorescently labelled quaternary-ammonium-beta-cyclodextrin monomer and polymer were selected for uptake studies in CACO-2 cells. The monomeric and polymeric beta-cyclodextrins were internalized in the cytoplasm of CACO-2 cells; the cationic monomer showed higher permeability than the hydroxypropyl-beta-cyclodextrin, employed as comparison. Therefore, these cationic beta-cyclodextrins showed potential as excipients able to improve the nasal absorption of drugs. Furthermore, amino-beta-cyclodextrin and beta-cyclodextrin soluble polymers were able to reduce oxidative damage in PC12 and CACO-2 cells and thus could be studied as bioactive carriers or potential drugs for cell protection against oxidative stress.

show abstract

“…Among the class of β-cyclodextrin derivatives, (2-hydroxypropyl) beta-cyclodextrin (HP) is an approved pharmaceutical excipient and its monograph has been published in both the European Pharmacopoeia and United States Pharmacopoeia [5]. HP is recognized also as an active pharmaceutical ingredient and received the orphan drug designation for the treatment of Niemann-Pick disease from the US FDA and the EMA [5][6][7][8]. Moreover, HP is able to provide protection against neurotoxicity induced by β-amyloid, and therefore useful in the treatment of Alzheimer's disease [8][9][10].…”

Section: Introductionmentioning

confidence: 99%

Investigation of Cytotoxicity and Cell Uptake of Cationic Beta-Cyclodextrins as Valid Tools in Nasal Delivery

Rassu¹,

Fancello²,

Roldo³

et al. 2020

Preprint

View full text Add to dashboard Cite

Cyclodextrin polymers have high applicability in pharmaceutical formulations due to better biocompatibility, solubility enhancement, loading capacity and controlled drug release than parent the cyclodextrins. The cytotoxicity and cell uptake of new cationic beta-cyclodextrin monomers and polymers were evaluated as suitable material for nasal formulations and their protective effects on cells exposed to hydrogen peroxide were studied. PC12 and CACO-2 cells were selected as the neuronal and epithelial type cells, respectively, to mimic the structure of respiratory and olfactory epithelia of the nasal cavity. All cationic beta-cyclodextrin polymers tested showed dose- and time-dependent toxicity; nevertheless, at 5 µM concentration and 60 min of exposure, the quaternary-ammonium-beta-cyclodextrin soluble polymer could be recognized as non-toxic. Based on these results, fluorescently labelled quaternary-ammonium-beta-cyclodextrin monomer and polymer were selected for uptake studies in CACO-2 cells. The monomeric and polymeric beta-cyclodextrins were internalized in the cytoplasm of CACO-2 cells; the cationic monomer showed higher permeability than the hydroxypropyl-beta-cyclodextrin, employed as comparison. Therefore, these cationic beta-cyclodextrins showed potential as excipients able to improve the nasal absorption of drugs. Furthermore, amino-beta-cyclodextrin and beta-cyclodextrin soluble polymers were able to reduce oxidative damage in PC12 and CACO-2 cells and thus could be studied as bioactive carriers or potential drugs for cells protection against oxidative stress.

show abstract

Cyclodextrins in Drug Delivery Systems and Their Effects on Biological Barriers

Cited by 129 publications

References 133 publications

Cyclodextrin Complexation Improves the Solubility and Caco-2 Permeability of Chrysin

Cyclodextrin Complexation Improves the Solubility and Caco-2 Permeability of Chrysin

Investigation of Cytotoxicity and Cell Uptake of Cationic Beta-Cyclodextrins as Valid Tools in Nasal Delivery

Investigation of Cytotoxicity and Cell Uptake of Cationic Beta-Cyclodextrins as Valid Tools in Nasal Delivery

Contact Info

Product

Resources

About