Aim: To evaluate a mixed micellar drug delivery system composed of sodium cholate and phospholipid for oral administration of silybin, a promising hepatoprotectants. Methods: The optimum formulation of sodium cholate/phospholipid-mixed micelles containing silybin was obtained based on the study of pseudo-ternary phase diagram. The dissolution of silybin-mixed micelles was investigated. The pharmacokinetic characteristics and bioavailability after oral administration of silybin-mixed micelles and silybin-N-methylglucamine were compared in dogs. Results: The mean particle size of prepared mixed micelles was 75.9±4.2 nm. The largest solubility of silybin was found to be 10.0±1.1 mg/mL in the optimum formulation of mixed micelles. The silybin-sodium cholate/phospholipid-mixed micelles showed a very slow release of silybin 17.5% (w/w) within 72 h in phosphate buffer (pH 7.4) and 15.6% (w/w) in HCl solution (pH 1.2). After oral administration to dogs, the relative bioavailability of mixed micelles versus silybin-N-methylglucamine in dogs was 252.0%. Conclusion: Sodium cholate/phospholipid-mixed micelles are promising carriers in orally delivery of silybin, considering their capability of enhancing bioavailability and large-scale production.

Aim: To formulate proliposomes with a polyphase dispersed system composed of soybean phospholipids, cholesterol, isopropyl myristate and sodium cholate to improve the oral bioavailability of dehydrosilymarin, an oxidized form of herbal drug silymarin. Methods: Dehydrosilymarin was synthesized from air oxidation of silymarin in the presence of pyridine, and proliposomes were prepared by a film dispersion-freeze drying method. Morphological characterization of proliposomes was observed using a transmission electron microscope. Particle size and encapsulation efficiency of proliposomes were measured. The in vitro release of dehydrosilymarin from suspension and proliposomes was evaluated. The oral bioavailability of dehydrosilymarin suspension and proliposomes was investigated in rabbits. Results: The proliposomes prepared under the optimum conditions were spherical and smooth with a mean particle size in the range of 7 to 50 nm. Encapsulation efficiency was 81.59%±0.24%. The in vitro accumulative release percent of dehydrosilymarinloaded proliposomes was stable, which was slow in pH 1.2, and increased continuously in pH 6.8, and finally reached 86.41% at 12 h. After oral administration in rabbits, the relative bioavailability of proliposomes versus suspension in rabbits was 228.85%. Conclusion: Proliposomes may be a useful vehicle for oral delivery of dehydrosilymarin, a drug poorly soluble in water.

The therapeutic efficiency of allogenic/intrinsic neural stem cells (NSCs) after spinal cord injury is severely compromised because the hostile niche at the lesion site incurs massive astroglial but not neuronal differentiation of NSCs. Although many attempts are made to reconstruct a permissive niche for nerve regeneration, solely using a living cell material to build an all‐in‐one, multifunctional, permissive niche for promoting neuronal while inhibiting astroglial differentiation of NSCs is not reported. Here, ectomesenchymal stem cells (EMSCs) are reported to serve as a living, smart material that creates a permissive, all‐in‐one niche which provides neurotrophic factors, extracellular matrix molecules, cell–cell contact, and favorable substrate stiffness for directing NSC differentiation. Interestingly, in this all‐in‐one niche, a corresponding all‐in‐one signal‐sensing platform is assembled through recruiting various niche signaling molecules into lipid rafts for promoting neuronal differentiation of NSCs, and meanwhile, inhibiting astrocyte overproliferation through the connexin43/YAP/14‐3‐3θ pathway. In vivo studies confirm that EMSCs can promote intrinsic NSC neuronal differentiation and domesticating astrocyte behaviors for nerve regeneration. Collectively, this study represents an all‐in‐one niche created by a single‐cell material—EMSCs for directing NSC differentiation.

These results indicate that the developed microemulsion represents a safe and orally effective carrier for poorly soluble substances. The formulation could be used for clinical trials and expand the application of capsaicin.

The PLGA nanoparticles serve as a promising carrier for the poorly soluble ergosterol and significantly improve its bioavailability, biodistribution and in vitro anti-tumor activities.