Preparation and in vitro and in vivo evaluation of quercetin-loaded mixed micelles for oral delivery.

Quercetin (QT) is a plant polyphenol with various pharmacological properties. However, the low water solubility limits its therapeutic efficacy. In the present study, QT-loaded sodium taurocholate-Pluronic P123 (QT-loaded ST/P123) mixed micelles were developed and characterized, and the effect of the formulation on improving the water solubility of QT was investigated. QT-loaded ST/P123 mixed micelles were prepared by thin film hydration-direct dissolution and optimized by uniform design. The optimal formulation possessed high drug loading (12.6%) and entrapment efficiency (95.9%) in small (16.20 nm) spherically-shaped micelles. A low critical micelle concentration indicated that the micelles were stable, and they showed a sustained release pattern, as determined in vitro in simulated gastric fluid and intestinal fluid. Pharmacokinetic evaluation showed the Cmax and AUC0-24 were 1.8-fold and 1.6-fold higher than the QT suspension. The present results indicate that QT-loaded ST/P123 micelles are potential candidates to improve the solubility and oral bioavailability of QT.

Dendritic cell-targeting polymer nanoparticle-based immunotherapy for cancer: A review.

Cancer immunity is dependent on dynamic interactions between T cells and dendritic cells (DCs). Polymer-based nanoparticles target DC receptors to improve anticancer immune responses. In this paper, DC surface receptors and their specific coupling natural ligands and antibodies are reviewed and compared. Moreover, reaction mechanisms are described, and the synergistic effects of immune adjuvants are demonstrated. Also, extracellular-targeting antigen-delivery strategies and intracellular stimulus responses are reviewed to promote the rational design of polymer delivery systems.

Azo modified hyaluronic acid based nanocapsules: CD44 targeted, UV-responsive decomposition and drug release in liver cancer cells.

Herein, we demonstrate a novel UV-induced decomposable nanocapsule of natural polysaccharide (HA-azo/PDADMAC). The nanocapsules are fabricated based on layer-by-layer co-assembly of anionic azobenzene functionalized hyaluronic acid (HA-azo) and cationic poly diallyl dimethylammonium chloride (PDADMAC). When the nanocapsules are exposed to 365 nm light, ultraviolet photons can trigger the photo-isomerization of azobenzene groups in the framework. The nanocapsules could decompose from large-sized nanocapsules to small fragments. Due to their optimized original size (~180 nm), the nanocapsules can effectively avoid biological barriers, provide a long blood circulation and achieve high tumor accumulation. It can fast eliminate nanocapsules from tumor and release the loaded drugs for chemotherapy after UV-induced dissociation. Besides, HA is an endogenous polysaccharide that shows intrinsic targetability to CD44 receptors on surface of cancer cells. The intracellular experiment shows that the HA-azo/PDADMAC nanocapsules with CD44 targeting ability and UV-controlled intracellular drug release are promising for cancer chemotherapy.

Characterization and antibacterial properties of epsilon-poly- l-lysine grafted multi-functional cellulose beads.

In recent years, harmful microorganisms in water pose great harm to ecological environment and human health. To solve this problem, epsilon-poly-l-lysine (EPL) grafted cellulose beads were prepared via 2, 2, 6, 6-tetramethylpiperidine-1-oxyl (TEMPO) mediated oxidation and carbodiimide mediated cross-linking reaction. Hydroxyl groups on C6 of cellulose were oxidized to carboxyl groups by TEMPO and grafting reaction was achieved between newly formed carboxyl groups of cellulose and amino of EPL. The beads were characterized by FTIR, SEM, XRD and TGA. The crystalline form of cellulose transformed from cellulose I to cellulose II after being dissolved and regenerated. The grafted cellulose beads showed good antibacterial activities against Gram-negative Escherichia coli, Gram-positive Staphylococcus aureus and Alicyclobacillus acidoterrestris with 10 h. The beads could be biodegraded in soil after 28 days. It is expected that the bio-based composite beads could have potential applications in water purification and food treatment fields.

Fabrication and characterization of antibacterial epsilon-poly-L-lysine anchored dicarboxyl cellulose beads.

Pathogens in the food and environment pose a great threat to human health. To solve this problem, we described a novel route to synthesize antibacterial epsilon-poly-L-lysine (EPL) anchored dicarboxyl cellulose beads. Cellulose beads were prepared via a sol-gel transition method and oxidized by sodium periodate and sodium chlorite to form carboxyl groups. EPL was anchored on the beads using carbodiimide mediated amidation. The structure and morphology of beads were characterized by FTIR, XPS, XRD, SEM, and TGA. After dissolution and regeneration, the crystalline form of cellulose is transformed from cellulose I to cellulose II. The thermal degradation temperature of the beads is 200∼300 °C.The samples displayed excellent antimicrobial activity against Staphylococcus aureus, Alicyclobacillus acidoterrestris and Escherichia coli within 12 h. The beads could be biodegraded in soil after 20 days. The biodegradable beads exhibited great potential in food and environmental applications.

Micelles modified with a chitosan-derived homing peptide for targeted intracellular delivery of ginsenoside compound K to liver cancer cells.

Ginsenoside compound K (CK), a major metabolite of protopanaxadiol ginsenosides, exhibits significant anticancer activities against various cancer cells. However, CK has poor water solubility and low bioavailability, which have limited its application. In this study, A54 peptide was utilized to fabricate CK-loaded micelles (APD-CK) for liver targeting, using deoxycholic acid-O-carboxymethyl chitosan as the vehicle. The average particle size of APD-CK micelles was about 171.4 nm by dynamic light scattering in the hydrated state and their morphology were spherical with good dispersion. An in vitro release assay indicated pH-responsive and sustained release behavior through a mechanism of non-Fickian diffusion. Moreover, the in vitro cytotoxicity of the APD-CK micelles against HepG2 and Huh-7 cells was significantly stronger than that of CK up to 20 µg/mL. Enhanced cellular uptake of micelles in both cell types was established using confocal fluorescence scanning microscopy and flow cytometry. In addition, western blot analysis revealed that APD-CK micelles could promote the protein expression levels of caspase-3, caspase-9, and poly (ADP-ribose) polymerase. Therefore, APD-CK micelles are a potential vehicle for delivering hydrophobic drugs in liver cancer therapy, enhancing drug targeting and anticancer activity.