Preparation and evaluation of icariside II-loaded binary mixed micelles using Solutol HS15 and Pluronic F127 as carriers

Abstract

An effective anti-cancer drug, icariside II (IS), has been used to treat a variety of cancers in vitro. However, its poor aqueous solubility and permeability lead to low oral bioavailability. The aim of this work was to use Solutol Õ HS15 and Pluronic F127 as surfactants to develop novel mixed micelles to enhance the oral bioavailability of IS by improving permeability and inhibiting efflux. The IS-loaded mixed micelles were prepared using the method of ethanol thin-film hydration. The physicochemical properties, dissolution property, oral bioavailability of the male SD rats, permeability and efflux of Caco-2 transport models, and gastrointestinal safety of the mixed micelles were evaluated. The optimized IS-loaded mixed micelles showed that at 4:1 ratio of Solutol Õ HS15 and Pluronic F127, the particle size was 12.88 nm with an acceptable polydispersity index of 0.172. Entrapment efficiency (94.6%) and drug loading (9.7%) contributed to the high solubility (11.7 mg/mL in water) of IS, which increased about 900-fold. The SF-IS mixed micelle release profile showed a better sustained release property than that of IS. In Caco-2 cell monolayer models, the efflux ratio dramatically decreased by 83.5%, and the relative bioavailability of the mixed micelles (AUC 0-1 ) compared with that of IS (AUC 0-1 ) was 317%, indicating potential for clinical application. In addition, a gastrointestinal safety assay also provided reliable clinical evidence for the safe use of this micelle.

TPGS-modified liposomes for the delivery of ginsenoside compound K against non-small cell lung cancer: formulation design and its evaluation in vitro and in vivo

“…The dialysis bag diffusion method was used to study the in vitro release behaviour of GCK from GCKT‐liposomes. Briefly, 5 ml of GCKT‐liposomes was placed into a dialysis bag (Mw = 3500 Da; Greenbird Inc, Shenzhen, China), hermetically sealed and immersed into 50 ml phosphate‐buttered saline (PBS, pH 7.4) medium containing 0.5% (w/v) Tween 80 at 37 °C. The entire system was stirred at 100 rpm/min for 24 h. At predetermined time intervals, 1 ml release medium was withdrawn at 15, 30 and 60 min or 4, 8, 12 and 24 h and filtered through 0.45 μm membrane before transferred into HPLC vial.…”

Enhancing the oral bioavailability of biochanin A by encapsulation in mixed micelles containing Pluronic F127 and Plasdone S630

“…23 In brief, BCA was dissolved in ethanol at a concentration of 5 mg/mL. F127 and S630 were combined in different ratios and dispersed in ethanol at 45°C.…”

“…Culture conditions for growing Caco-2 cells were the same as in our previous studies. 23 Briefly, Caco-2 cells were grown in high-glucose Dulbecco's Modified Eagle's Medium at 37°C in a 5% CO 2 atmosphere and at a relative humidity of 95%, supplemented with 10% fetal bovine serum, 1% minimal essential medium non-essential amino acids, 2 mM l-glutamine, and 1% penicillin/streptomycin. Cells were seeded at a density of 1×10 6 cells/cm 2 on untreated culture inserts of polycarbonate membranes with 0.4 μm pores.…”

“…[20][21][22] Because of the copolymerization, Plasdone S630 retains the merits of PVP, such as good solubility in water, good film formation, and better bonding performance, and incorporates extensive drug solubilization capacity and better surface activity derived from VA. Therefore, based on our previous studies, 23,24 we speculated that the new combination of binary mixed micelles could enhance the aqueous solubility of BCA and improve its oral bioavailability.…”

Insulin-loaded PLGA microspheres for glucose-responsive release

“…In recent decades, a range of long term sustained-release materials have been reported (Hou et al, 2016;Huang et al, 2016;Maulvi et al, 2016). These are commonly based on PLGA, which is a generally recognized as safe (GRAS) excipient certified by the FDA.…”