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Background Targeted prodrug has various applications as drug formulation for tumor therapy. Therefore, amphoteric small-molecule prodrug combined with nanoscale characteristics for the self-assembly of the nano-drug delivery system (DDS) is a highly interesting research topic. Methods and results In this study, we developed a prodrug self-assembled nanoplatform, 2-glucosamine-fluorescein-5(6)-isothiocyanate-glutamic acid-paclitaxel (2DA-FITC-PTX NPs) by integration of targeted small molecule and nano-DDS with regular structure and perfect targeting ability. 2-glucosamine (DA) and paclitaxel were conjugated as the targeted ligand and anti-tumor chemotherapy drug by amino acid group. 2-DA molecular structure can enhance the targeting ability of prodrug-based 2DA-FITC-PTX NPs and prolong retention time, thereby reducing the toxicity of normal cell/tissue. The fluorescent dye FITC or near-infrared fluorescent dye ICG in prodrug-based DDS was attractive for in vivo optical imaging to study the behavior of 2DA-FITC-PTX NPs. In vitro and in vivo results proved that 2DA-FITC-PTX NPs exhibited excellent targeting ability, anticancer activity, and weak side effects. Conclusion This work demonstrates a new combination of nanomaterials for chemotherapy and may promote prodrug-based DDS clinical applications in the future.

Purpose: We aimed to prepare two oral drug delivery systems consisting of polyoxyl 15 hydroxystearate (HS15) with pluronicF127 (F127) and HS15 with pluronicL61 (L61) to overcome the challenges of genistein's poor oral bioavailability. This provides a good strategy for enhancing the potential value of genistein. Methods: We designed two binary mixed micelle systems employing the organic solvent evaporation method using surfactants (HS15, L61, and F127). Formulations (GEN-F and GEN-L) were characterized by transmission electron microscopy. Drug content analysis, including entrapment efficiency (EE%), drug loading (DL%), and the cumulative amount of genistein released from the micelles, was performed using HPLC. The permeability of optimum formulation was measured in Caco-2 cell monolayers, and the oral bioavailability was evaluated in SD rats. Results: The solutions of GEN-F and GEN-L were observed to be transparent and colorless. GEN-F had a lower EE% of 80.79±0.55% and a DL% of 1.69±0.24% compared to GEN-L, which had an EE% 83.40±1.36% and a DL% 2.26±0.18%. TEM results showed that the morphology of GEN-F and GEN-L was homogeneous and resembled a spherical shape. The dilution and storage conditions had no significant effect on particle size and EE%. Genistein demonstrated a sustained release behavior when encapsulated in micelles. Pharmacokinetics study showed that the relative oral bioavailability of GEN-F and GEN-L increased by 2.23 and 3.46 fold while also enhancing the permeability of genistein across a Caco-2 cell monolayer compared to that of raw genistein. Conclusion: GEN-F and GEN-L as a drug delivery system provide an effective strategy for enhancing and further realizing the potential value of GEN.

Objectives To increase the solubility of baicalein (BAI) by preparing BAI-micelles (BAI-M) with Solutol HS15 (HS15) and Poloxamer 188 (F68), thereby improving its oral bioavailability. Methods Baicalein micelles were prepared with HS15 and F68 by thin-film dispersion method and optimized by central composite design (CCD) approach. Physicochemical, in vitro release, Caco-2 cell transport and pharmacokinetic studies of BAI-M were performed. Key findings The optimal formulation showed spherical shape by characterization of the transmission electron microscope with average small size (23.14 ± 1.46 nm) and high entrapment efficiency (92.78±0.98%) and drug loading (6.45±1.54%). The in vitro release study of BAI-M showed a significantly sustained release pattern compared with free BAI. Caco-2 cell transport study demonstrated that high permeability of BAI was achieved after loading it into micelles. Meanwhile, pharmacokinetics study of BAI-M showed a 3.02-fold increase in relative oral bioavailability compared with free BAI. Conclusions Based on our findings, we concluded that HS15 can be used as a carrier in this drug delivery system that includes F68, and BAI-M has great potential in improving solubility and oral bioavailability.

Genistein (GEN), is a natural dietary isoflavone, has been reported to show anticancer activities. However, its poor aqueous solubility and oral bioavailability limit its clinical application. We designed a novel genistein-loaded mixed micelles (GEN-M) system composed of Soluplus® and Vitamin E d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) were prepared by organic solvent evaporation aimed to overcome the challenges of GEN's poor solubility and then further improve its oral bioavailability. The optimized, spherical-shaped GEN-M was obtained at a ratio of 10:1 (Soluplus®:TPGS). The mean particle size of GEN-M was 184.7 ± 2.8 nm, with a narrow polydispersity index (PDI) of 0.162 ± 0.002. The zeta potential value of GEN-M was -2.92 ± 0.01 mV. The micelles solutions was transparent with blue opalescence has high the entrapment efficiency (EE) and drug loading (DL) of 97.12 ± 2.11 and 3.87 ± 1.26%, respectively. GEN-M was demonstrated a sustained release behavior when formed micelles shown in drug release in vitro. The solubility of GEN in water increased to 1.53 ± 0.04 mg/mL after encapsulation. The permeability of GEN across a Caco-2 cell monolayer was enhanced, and the pharmacokinetics study of GEN-M showed a 2.42-fold increase in relative oral bioavailability compared with free GEN. Based on these findings, we conclude that this novel nanomicelles drug delivery system could be leveraged to deliver GEN and other hydrophobic drugs.

Objectives We aimed to prepare novel magnolol-loaded mixed micelles (MAG-M) by pluronic F127 and L61 to overcome the challenges of magnolol's poor solubility and then further improve its oral bioavailability. Methods Magnolol-loaded mixed micelles containing pluronic F127 and L61 were prepared by an organic solvent evaporation method. Physicochemical, transport experiment across Caco-2 cell monolayers and pharmacokinetic studies were performed to characterize MAG-M and to determine the final improvement of the oral bioavailability. Key findings The MAG-M solution was transparent and colourless with average size, polydispersity index and zeta potential of 228.0 ± 2.1 nm, 0.298 ± 0.012 and −0.89 ± 0.02 mV. The micelle solution has a higher EE% and DL% of 81.57 ± 1.49% and 27.58 ± 0.53%, respectively. TEM result showed that the morphology of MAG-M was homogeneous and spherical shape. The dilution stability of MAG-M was no significant change in particle size and entrapment efficiency. MAG was demonstrated a sustained-release behaviour after encapsulated in micelles. MAG permeability across a Caco-2 cell monolayer was enhanced, and the pharmacokinetics study of MAG-M showed a 2.83-fold increase in relative oral bioavailability compared with raw MAG. Conclusions The mixed micelles containing pluronic F127 and L61 as drug delivery system provided a well strategy for resolving the poor solubility and bioavailability problems of MAG.

Objectives With the purpose of developing a curcumin phospholipid complex (CPC) formulation with high performance, the CPC was prepared and solidified with Soluplus® in this study. Methods Soluplus® was used as a carrier to solidify CPC. The structures of the CPC and curcumin phospholipid complex – Soluplus® solidified powder (CSP) – were also characterized by differential scanning electron microscope, differential scanning calorimetry, Fourier transform infrared spectroscopy and X-ray diffractometer, and flowability, in-vitro dissolution and oral bioavailability were also investigated. Key findings All analysis indicated that curcumin was completely converted from crystalline to amorphous state in solidified powder. The angle of repose calculated in flowability study indicated a marked improvement from ‘cannot be measured’ to ‘37°’. Meanwhile, the dissolution study showed that in phosphate buffer condition, the dissolution rate of CSP had released 76.34% in pH 6.8 and the 78.19% in pH 1.2. Furthermore, in pharmacokinetic study, significant (P < 0.01) improvement of AUC0–∞ value was observed between CPC and CSP groups, and the results showed that AUC0–∞ value was increased from 205.84 ± 50.46 μg h/ml to 330.47 μg h/ml. Conclusions A simple and convenient solidifying process was used in this study, and the data suggested that this process not only could improve the flowability and dissolution of phospholipid complex, but also increased the oral bioavailability of curcumin.

The aim of this study was to prepare two novel magnolol (MO)-loaded binary mixed micelles (MO-M) using biocompatible copolymers of Soluplus (SOL) and Solutol® HS15 (HS15), SOL and d-alpha-tocophery...

In this study, a novel ternary complex system (TCS) composed of baicalein, phospholipids, and Soluplus was prepared to improve the flowability and dissolution for baicalein phospholipid complex (BPC). TCS was characterized using differential scanning calorimetry (DSC), infrared spectroscopy (IR), powder X-ray diffraction (PXRD), and scanning electron microscopy (SEM). The flowability, solubility, oil–water partition coefficient, in vitro dissolution, and in vivo pharmacokinetics of the system were also evaluated. DSC, IR, PXRD, and SEM data confirmed that the crystal form of baicalein disappeared in BPC and TCS. Furthermore, the angle of repose of TCS of 35° indicated an improvement in flowability, and solubility increased by approximately eight-fold in distilled water when TCS was compared with BPC (41.00 ± 4.89 μg/mL vs. 5.00 ± 0.16 μg/mL). Approximately 91.24% of TCS was released at the end of 60 min in 0.5% SDS (pH = 6.8), which suggested that TCS could improve the dissolution velocity and extent. Moreover, TCS exhibited a considerable enhancement in bioavailability with higher peak plasma concentration (25.55 μg/mL vs. 6.05 μg/mL) and increased AUC0–∞ (62.47 μg·h/mL vs. 50.48 μg·h/mL) with 123.75% relative bioavailability compared with BPC. Thus, Soluplus achieved the purpose of improving the flowability and solubility of baicalein phospholipid complexes. The application of Soluplus to phospholipid complexes has great potential.

Weikang Keli (constitutes of Root of Codonopsis pilosula, Rhizoma Atractylodis Macrocephalae, Rhizoma Curcumae Aeruginosae, Rhizoma Pinelliae, Actinidia chinensis Planch, and Rhodiola rosea) is a well known Chinese herbal formula for gastric cancer therapy in clinical treatment. However, the detailed molecular mechanisms involved are still not fully understood. In this study, we found that Weikang Keli could induce patterns of autophagy in SGC-7901 cells, including intracellular vacuole formation, microtubule-associated protein 1 light chain 3 (LC3) conversion. Hoechst 33258 staining and Western blot analysis of apoptosis-related proteins showed that WK induced SGC-7901 cell death was not through apoptosis. In vivo study also revealed that i.g. administration of Weikang Keli once a day for 25 days could significantly reduce tumor volumes by about 50%. Collectively, the current data indicated that Weikang Keli induced gastric cancer cell death by autophagy effects.