Enhancing oral bioavailability of quercetin using novel soluplus polymeric micelles

Dian, Linghui; En-jiang, YU; Chen, Xiaona; Wen, Xinguo; Zhang, Zhengzan; Qin, Lingzhen; Wang, Qingqing; Li, Ge; Wu, Chuanbin

doi:10.1186/1556-276x-9-684

Cited by 178 publications

(90 citation statements)

References 40 publications

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“…9,10) The copolymer exhibits an amphipathic property attributed to its hydrophilic and hydrophobic residues, which could contribute to the formation of micelles in water. Unlike conventional polymers such as polyvinylpyrrolidone and hydroxypropyl methylcellulose, Soluplus ® is bifunctional and can act as both a polymeric carrier of solid dispersions and as a solubilizer through the formation of micelles in water, [11][12][13] which could be useful for the production of highly water-soluble formulations. Furthermore, the polymer has an inherent binding site that allows hydrogen bonding and/or van der Waal's interactions with drug molecules, which can lead to the stabilization of the drug molecule in the matrix.…”

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confidence: 99%

Evaluation of the Micellization Mechanism of an Amphipathic Graft Copolymer with Enhanced Solubility of Ipriflavone

et al. 2016

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The main purpose of this study was to investigate the solubilization enhancement properties of an amphipathic graft copolymer, Soluplus ® , on test compounds. Micellization of Soluplus ® in solution was characterized by evaluating the changes in the surface activity, turbidity, and thermodynamic behavior. To assess the feasibility of Soluplus ® as a polymeric carrier of solid dispersions, freeze-dried samples of ipriflavone were prepared, and the physicochemical properties of the carrier plus ipriflavone were evaluated in terms of solubility, dissolution, and crystallinity. The surface tension of the solution decreased depending on the polymer concentration, and gradual turbidity increase was observed. Isothermal titration calorimetry was used to measure the thermal reaction accompanying the micellization of Soluplus ® and indicated that a colloidal micelle formation improved solubility. The prepared formulations, particularly at a ratio of ipriflavone : Soluplus ® 1 : 10 (w/w) exhibited a dramatically improved solubility of ipriflavone that was ca. 70-fold higher than that of untreated ipriflavone. The solubilization mechanism of Soluplus ® was partially elucidated and suggested that its strategic application could improve the solubility of hydrophobic compounds.Key words isothermal titration calorimetry; ipriflavone; amphipathic graft copolymer; solubility Among the available technologies, the solid dispersion technique is commonly used as one of the most promising strategies for the enhancement of the solubility, dissolution rate, and bioavailability of poorly water-soluble compounds. A solid dispersion system can be defined as a distribution of active pharmaceutical ingredients as molecular amorphous particles and/or in the microcrystalline state into a carrier matrix-like polymer.1) The physicochemical characteristics of polymeric carriers could dominate the pharmaceutical properties of a solid dispersion system. 2,3) Based on the characteristic properties of a polymeric carrier, a number of solid dispersion systems possessing various functional properties such as sustained release, pH-dependent release, self-emulsifying properties, and site-specific release have been developed. [4][5][6][7] In particular, amphiphilic polymers have been found to be beneficial for the enhancement of not only solubility but also of the oral bioavailability of poorly water-soluble compounds because they form micellar structures that contain the compound. 6,8) Soluplus ® , a graft copolymer consisting of polyvinyl caprolactam, polyvinyl acetate, and polyethyleneglycol, has been applied to the design of solid-dispersion formulations with poorly water-soluble substances to improve their solubility and bioavailability.9,10) The copolymer exhibits an amphipathic property attributed to its hydrophilic and hydrophobic residues, which could contribute to the formation of micelles in water. Unlike conventional polymers such as polyvinylpyrrolidone and hydroxypropyl methylcellulose, Soluplus ® is bifunctional and can act as both a polym...

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confidence: 99%

Evaluation of the Micellization Mechanism of an Amphipathic Graft Copolymer with Enhanced Solubility of Ipriflavone

et al. 2016

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“…Second, because of the viscosity properties of Sco-Ms, the Sco-Ms could adhere to the intestines and increase the contact area and contact time between the drug and GI tract, which contributed to the enhanced absorption of scopoletin. Third, studies have reported that nanoparticles with sizes approximately at or below 100 nm show optimum cellular and nuclear uptake in smooth muscle and epithelial cells [20,32] . In addition, another previous study indicated that phase II metabolism might be one of the reasons for the poor bioavailability of scopoletin [14] .…”

Section: Discussionmentioning

confidence: 99%

“…Three groups of rats were orally administered with scopoletin suspension, Sco-PM or Sco-Ms at an equivalent dose of 100 mg/kg scopoletin. The blood samples (approximately 0.3 mL) were collected via the orbital venous plexus at predetermined time intervals (2,5,10,15,20,30,45,60,90, and 120 min). All blood samples were immediately centrifuged at 3000×g for 5 min, and then the plasma supernatant was collected.…”

Section: Pharmacokinetic and Biodistribution Studymentioning

confidence: 99%

“…Due to its high fluidity and excellent extrudability, Soluplus shows superior performance in forming solid solutions, especially in hot melt extrusion processes [17,18] . As an amphiphile, Soluplus has been extensively used to improve the aqueous solubility and oral bioavailability of poorly soluble drugs [19] , and it can self-assemble into micelles above the critical micelle concentration (CMC) [20] . In the present study, Soluplus-based micelles were applied for the first time to encapsulate scopoletin.…”

Section: Introductionmentioning

confidence: 99%

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Soluplus micelles for improving the oral bioavailability of scopoletin and their hypouricemic effect in vivo

Zeng

Liu

et al. 2017

Acta Pharmacol Sin

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Scopoletin is an active coumarin possessing a variety of pharmacological activities, including anti-hyperuricemic effect, but with poor solubility. To improve its oral bioavailability, we attempted to encapsulate scopoletin into Soluplus micelles (Soluplus-based scopoletin micelles, Sco-Ms) and evaluated the hypouricemic action of Sco-Ms. Sco-Ms were prepared using a thin-film hydration method. Sco-Ms displayed near spherical shapes with an average size of 59.4±2.4 nm (PDI=0.08±0.02). The encapsulation efficiency of scopoletin was 87.3%±1.5% with a loading capacity of 5.5%±0.1%. Sco-Ms were further characterized using transmission electron microscopy, powder X-ray diffraction, Fourier transform infrared techniques and scanning electron microscopy. After oral administration in rats, Sco-Ms exhibited significantly improved absorption in each intestinal segment compared to free scopoletin, with the duodenum and jejunum being the main absorption regions. In rats administered Sco-Ms (at an equivalent dose of free scopoletin of 100 mg/kg, po), the AUC 0-∞ and C max of Sco-Ms were 4.38-and 8.43-fold, respectively, as large as those obtained following administration of free scopoletin. After oral administration in rats, Sco-Ms did not alter the tissue distributions of scopoletin, but significantly increased the scopoletin levels in the liver. In potassium oxonate-induced hyperuricemic mice, oral administration of Sco-Ms (at an equivalent dose of free scopoletin of 300 mg/kg) reduced the serum uric acid concentration to the normal level. The results suggest that Soluplus-based micelle system greatly improves the bioavailability of poorly water-soluble drugs, such as scopoletin, and represents a promising strategy for their oral delivery.

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“…6,7 Micelles formulated with soluplus have a low critical micelle concentration value (about 10 -8 M) and small in size (~65 nm). 7 In the molecular structure, soluplus has a hydrophilic polyethylene glycol backbone and several hydrophobic vinylcaprolactam/vinyl acetate side chains. Its hydrophobic carbonyl group can form hydrogen bonds with the hydroxyl groups of drug molecules, thus increasing the drug loading (DL) capacity and the stability of the micelles.…”

Section: Introductionmentioning

confidence: 99%

Fabrication of paclitaxel hybrid nanomicelles to treat resistant breast cancer via oral administration

Dian

Lin

et al. 2018

IJN

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Aim Oral chemotherapy using anticancer drugs would improve the clinical practice and the life quality of patients. The aim of the present study was to develop paclitaxel hybrid nanomicelles for oral administration to treat resistant breast cancer. Methods Evaluations were performed on human breast cancer MCF-7 cells, drug-resistant breast cancer MCF-7/Adr cells, and in MCF-7/Adr-xenografted BALB/c nude mice. The nanomicelles were composed of the polymer soluplus, d-α-tocopheryl polyethyleneglycol 1000 succinate (TPGS 1000 ), and dequalinium (DQA). The constructed paclitaxel hybrid nanomicelles were ~65 nm in size. Results The nanomicelles improved cellular uptake and anticancer efficacy in the resistant breast cancer cells and induced mitochondria-mediated apoptosis. The mechanism of the apoptosis-inducing effect was related to the co-localization of the nanomicelles with mitochondria; the activation of pro-apoptotic protein Bax, cytochrome C, and apoptotic enzymes caspase 9 and 3; and the inhibition of anti-apoptotic proteins Bcl-2 and Mcl-1. Oral administration of paclitaxel hybrid nanomicelles had the same anticancer efficacy as the intravenous injection of taxol in resistant breast cancer-bearing mice. The oral suitability of this formulation was associated with the nanostructure and the actions of TPGS 1000 and DQA. Conclusion The fabricated paclitaxel hybrid nanomicelles could provide a promising oral formulation to treat drug-resistant breast cancer.

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Enhancing oral bioavailability of quercetin using novel soluplus polymeric micelles

Cited by 178 publications

References 40 publications

Evaluation of the Micellization Mechanism of an Amphipathic Graft Copolymer with Enhanced Solubility of Ipriflavone

Evaluation of the Micellization Mechanism of an Amphipathic Graft Copolymer with Enhanced Solubility of Ipriflavone

Soluplus micelles for improving the oral bioavailability of scopoletin and their hypouricemic effect in vivo

Fabrication of paclitaxel hybrid nanomicelles to treat resistant breast cancer via oral administration

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