Preliminary Safety Evaluation of Parenterally Administered Sulfoalkyl Ether β-Cyclodextrin Derivatives

Lipophilic drugs have limited solubility in phospholipid systems, hence maximum entrapment levels in liposomes are known to be low. Barbigerone (Bar), an anticancer isoflavone, is water insoluble and an effective delivery route is through encapsulation in cyclodextrins (CDs) followed by a second encapsulation in liposomes. In this study, Bar or its inclusion complex [Bar/2-hydroxypropyl-b-CD (HP-b-CD)] were incorporated into liposomes prepared by the ethanol injection method. A 4.6-fold increase of encapsulation efficiency was achieved for the liposome-Bar/ HP-b-CD complex (Bar/HP-b-CD/liposome) in comparison with the conventional Bar/liposome. The size of the Bar/HPb-CD/liposome was 87.76 ± 1.45 nm and the zeta potential was -35.02 ± 0.50 mV. In addition, the liposomes remained stable in liquid form at 4°C for at least 3 months. The Bar/HP-b-CD/liposome was evaluated for anti-cancer activity in hepatocarcinoma HepG2 and colon cancer C26 cells and showed comparable toxicity to that of plain Bar. In vivo studies in hepatic cancer xenografted nude mice model showed that Bar/HP-b-CD/liposome significantly inhibited tumor growth with a substantial increase in animal survival. In conclusion, the encapsulation of the Bar/HP-b-CD complex into liposomes could provide an alternative means for its potential use in cancer therapy.

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“…CDs have been reported to cause hemolysis [19,20]. Thus, the hemolytic activity of Bar/HP-b-CD/liposomes was tested based on ChP.…”

Section: Hemolysismentioning

confidence: 99%

Barbigerone-in-hydroxypropyl-β-cyclodextrin-liposomal nanoparticle: preparation, characterization and anti-cancer activities

Qiu

Cai

Wang

et al. 2015

J Incl Phenom Macrocycl Chem

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“…This macrocycle exhibits solubility and complexing abilities greater than those of the parent CyDs [25,26]. In particular, when used as solubility enhancer, SBE-b-CyD has been shown to be clinically less toxic than b-CyD, not only in oral dosage form but also in other pharmaceutical applications [27][28][29][30]. Recently, Xiao et al [31] apply very powerful and well-assessed methodologies for the investigation in both liquid and solid state of the inclusion complexes of dihydroartemisinin with b-CyD and SBE-b-CyD.…”

Section: Introductionmentioning

confidence: 99%

Isoflavone aglycons-sulfobutyl ether-β-cyclodextrin inclusion complexes: in solution and solid state studies

Stancanelli

Venuti

Arigò

et al. 2015

J Incl Phenom Macrocycl Chem

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The effect of a polyanionic variably substituted sulfobutyl ether-b-cyclodextrin (SBE-b-CyD), complexation on the UV absorption of genistein (Gen) and daidzein (Dai) was studied in pure water. A phase solubility study was performed, according to the method reported by Higuchi and Connors, to evaluate the changes of isoflavones in the complexation state and type-A L solubility diagrams for both isoflavones were obtained suggesting that they form complexes with 1:1 molar ratio. These results were confirmed by Job's plot method. Complexation strongly increases the water solubility of isoflavones. The in vitro dissolution of isoflavones entrapped into SBE-b-CyD significantly surpassed that of the free isoflavones (over 90 % of the loaded Gen and Dai dissolved in 15 and 30 min, respectively). Finally, 1:1 molar ratio solid complexes were prepared by the kneading method and characterized in solid state by FTIR-ATR spectroscopy, with particular regard to O-H and C=O stretching vibrations, achieving structural information on the modifications induced by complexation on the H-bond scheme, also by applying band decomposition and curve-fit.

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“…Recently, several synthetically modified β-CD s, such as hydroxypropyl-b-cyclodextrin (HP-β-CD) and sulfobutyl ether-b-cyclodextrin (SBE-β-CD) have been made to improve the inclusion capacity and the physicochemical properties of parent CDs. They have been reported on account of their high solubility in water (excess 70 g/100 ml for SBE-β-CD and 65 g/ 100 ml for HP-β-CD at 25°C) and minimal toxicity [11][12][13]. Especially, SBE-β-CD, which is currently used in five commercially approved injectable products in the USA, has been recently been used to stabilize drugs and is currently undergoing extensive chronic safety assessment [14].…”

Section: Introductionmentioning

confidence: 99%

Effects of the Preparation Method on the Formation of True Nimodipine SBE-β-CD/HP-β-CD Inclusion Complexes and Their Dissolution Rates Enhancement

et al. 2014

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Abstract. The aims of this study were to enhance the solubility and dissolution rate of nimodipine (ND) by preparing the inclusion complexes of ND with sulfobutylether-b-cyclodextrin (SBE-β-CD) and 2-hydroxypropyl-b-cyclodextrin (HP-β-CD) and to study the effect of the preparation method on the in vitro dissolution profile in different media (0.1 N HCl pH 1.2, phosphate buffer pH 7.4, and distilled water). Thus, the inclusion complexes were prepared by kneading, coprecipitation, and freeze-drying methods. Phase solubility studies were conducted to characterize the complexes in the liquid state. The inclusion complexes in the solid state were investigated with differential scanning calorimetry (DSC), Xray diffractometry (X-RD), and Fourier transform infrared spectroscopy (FT-IR). Stable complexes of ND/SBE-β-CD and ND/HP-β-CD were formed in distilled water in a 1:1 stoichiometric inclusion complex as indicated by an A L -type diagram. The apparent stability constants (Ks) were 1334.4 and 464.1 M −1 for ND/SBE-β-CD and ND/HP-β-CD, respectively. The water-solubility of ND was significantly increased in an average of 22-and 8-fold for SBE-β-CD and HP-β-CD, respectively. DSC results showed the formation of true inclusion complexes between the drug and both SBE-β-CD and HP-β-CD prepared by the kneading method. In contrast, crystalline drug was detectable in all other products. The dissolution studies showed that all the products exhibited higher dissolution rate than those of the physical mixtures and ND alone, in all mediums. However, the kneading complexes displayed the maximum dissolution rate in comparison with drug and other complexes, confirming the influence of the preparation method on the physicochemical properties of the products.

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Preliminary Safety Evaluation of Parenterally Administered Sulfoalkyl Ether β-Cyclodextrin Derivatives

Cited by 130 publications

References 16 publications

Barbigerone-in-hydroxypropyl-β-cyclodextrin-liposomal nanoparticle: preparation, characterization and anti-cancer activities

Barbigerone-in-hydroxypropyl-β-cyclodextrin-liposomal nanoparticle: preparation, characterization and anti-cancer activities

Isoflavone aglycons-sulfobutyl ether-β-cyclodextrin inclusion complexes: in solution and solid state studies

Effects of the Preparation Method on the Formation of True Nimodipine SBE-β-CD/HP-β-CD Inclusion Complexes and Their Dissolution Rates Enhancement

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