Donghui Song

Quercetin-Containing Self-Nanoemulsifying Drug Delivery System for Improving Oral Bioavailability

Quercetin is a dietary flavonoid with potential chemoprotective effects, but has low bioavailability because of poor aqueous solubility and low intestinal absorption. A quercetin-containing self-nanoemulsifying drug delivery system (Q-SNEDDS) was developed to form oil-in-water nanoemulsions in situ for improving quercetin oral bioavailability. On the basis of the quercetin solubility, emulsifying ability, and stability after dispersion in an aqueous phase, an optimal SNEDDS consisting of castor oil, Tween® 80, Cremophor® RH 40, and PEG 400 (20:16:34:30, w/w) was identified. Upon mixing with water, Q-SNEDDS formed a nanoemulsion having a droplet size of 208.8 ± 4.5 nm and zeta potential of -26.3 ± 1.2 mV. The presence of Tween® 80 and PEG 400 increased quercetin solubility and maintained supersaturated quercetin concentrations (5 mg/mL) for >1 month. The optimized Q-SNEDDS significantly improved quercetin transport across a human colon carcinoma (Caco-2) cell monolayer. Fluorescence imaging demonstrated rapid absorption of the Q-SNEDDS within 40 min of oral ingestion. Following oral administration of Q-SNEDDS in rats (15 mg/kg), the area under the concentration curve and maximum concentration of plasma quercetin after 24 h increased by approximately twofold and threefold compared with the quercetin control suspension. These data suggest that this Q-SNEDDS formulation can enhance the solubility and oral bioavailability of quercetin for appropriate clinical application.

Long circulating self-assembled nanoparticles from cholesterol-containing brush-like block copolymers for improved drug delivery to tumors.

Amphiphilic brush-like block copolymers composed of polynorbonene-cholesterol/poly(ethylene glycol) (P(NBCh9-b-NBPEG)) self-assembled to form a long circulating nanostructure capable of encapsulating the anticancer drug doxorubicin (DOX) with high drug loading (22.1% w/w). The release of DOX from the DOX-loaded P(NBCh9-b-NBPEG) nanoparticles (DOX-NPs) was steady at less than 2% per day in PBS. DOX-NPs were effectively internalized by human cervical cancer cells (HeLa) and showed dose-dependent cytotoxicity, whereas blank nanoparticles were noncytotoxic. The DOX-NPs demonstrated a superior in vivo circulation time relative to that of free DOX. Tissue distribution and in vivo imaging studies showed that DOX-NPs preferentially accumulated in tumor tissue with markedly reduced accumulation in the heart and other vital organs. The DOX-NPs greatly improved survival and significantly inhibited tumor growth in tumor-bearing SCID mice compared to that for the untreated and free DOX-treated groups. The results indicated that self-assembled P(NBCh9-b-NBPEG) may be a useful carrier for improving tumor delivery of hydrophobic anticancer drugs.

A Biocompatible and Biodegradable Protein Hydrogel with Green and Red Autofluorescence: Preparation, Characterization and In Vivo Biodegradation Tracking and Modeling

Because of its good biocompatibility and biodegradability, albumins such as bovine serum albumin (BSA) and human serum albumin (HSA) have found a wide range of biomedical applications. Herein, we report that glutaraldehyde cross-linked BSA (or HSA) forms a novel fluorescent biological hydrogel, exhibiting new green and red autofluorescence in vitro and in vivo without the use of any additional fluorescent labels. UV-vis spectra studies, in conjunction with the fluorescence spectra studies including emission, excitation and synchronous scans, indicated that three classes of fluorescent compounds are presumably formed during the gelation process. SEM, FTIR and mechanical tests were further employed to investigate the morphology, the specific chemical structures and the mechanical strength of the as-prepared autofluorescent hydrogel, respectively. Its biocompatibility and biodegradability were also demonstrated through extensive in vitro and in vivo studies. More interestingly, the strong red autofluorescence of the as-prepared hydrogel allows for conveniently and non-invasively tracking and modeling its in vivo degradation based on the time-dependent fluorescent images of mice. A mathematical model was proposed and was in good agreement with the experimental results. The developed facile strategy to prepare novel biocompatible and biodegradable autofluorescent protein hydrogels could significantly expand the scope of protein hydrogels in biomedical applications.

Self-healing of thermally-induced, biocompatible and biodegradable protein hydrogel

Serum albumin is the most abundant protein in the circulatory system to transport fatty acids, metabolites and drugs. In this study, a highly biocompatible protein hydrogel was prepared from bovine serum albumin (BSA) via thermal treatment. A circular dichroism study indicates that thermally-induced partial unfolding of the protein molecules exposes the buried hydrophobic groups in the core to the environment, thus leading to the formation of fine stranded 3-D networks. By controlling the heating temperature and protein concentration, the mechanical strength and structural stability of the as-prepared BSA hydrogel can be facilely manipulated. The moderate denaturation of the protein within the hydrogel system allows repetitive self-healing after damage when moderate heat was induced. The tensile strength and break strain of fully healed protein hydrogel were recovered to almost 100% of the original strength and elongation abilities. Additionally, the good biocompatibility of this hydrogel system was demonstrated through in vitro cytotoxicity analysis first. Furthermore, in vivo experiments using immunocompetent mice show that the subcutaneously injected hydrogel in mice can be fully degraded with negligible acute inflammatory response, indicating excellent in vivo biocompatibility. These features indicate that the as-developed self-healing protein hydrogel system with good biocompatibility and biodegradability holds great potential in the field of biomedical engineering.

Novel green and red autofluorescent protein nanoparticles for cell imaging and in vivo biodegradation imaging and modeling

Albumins are widely used in bioengineering due to their low-cost, good biocompatibility and biodegradability. Herein we report that cross-linked bovine serum albumin (BSA) forms a suspension of novel fluorescent nanoparticles with an average size of ∼40 nm, exhibiting strong green/red autofluorescence. UV-vis spectra, in conjunction with fluorescence emission spectra, suggest that three classes of fluorescent compounds presumably formed during the preparation. The size distribution and surface morphology of the autofluorescent BSA nanoparticles were characterized using various advanced techniques. After removal of excessive cross-linking agent through dialysis, the autofluorescent BSA nanoparticles were first demonstrated for cell bioimaging application using 293FT human kidney cell line. Its good biocompatibility and low cytotoxicity were further validated by an in vitro cytotoxicity assay and an in vivo histological study. The strong red autofluorescence of the BSA nanoparticles was further exploited in the realization of convenient and non-invasive tracking/modeling of its in vivo degradation based on real-time fluorescence imaging. A mathematical model was proposed and in good agreement with the experimental results. This study indicates that the as-prepared functional, biocompatible and biodegradable autofluorescent protein nanoparticles are suitable for a range of biomedical applications.

A high-performance electrochemical sensor for biologically meaningful l-cysteine based on a new nanostructured l-cysteine electrocatalyst

As a new class of l-cysteine electrocatalyst explored in this study, Au/CeO2 composite nanofibers (CNFs) were employed to modify the screen printed carbon electrode (SPCE) to fabricate a novel l-cysteine (CySH) electrochemical sensor with high performance. Its electrochemical behavior and the roles of Au and CeO2 in the composite toward electro-oxidation of CySH were elucidated and demonstrated using cyclic voltammetry and amperometry techniques for the first time through the comparison with pure CeO2 NFs. More specifically, the Au/CeO2 CNFs modified SPCE possessed greatly enhanced electrocatalytic activity toward CySH oxidation. An ultra high sensitivity of 321 μA mM-1cm-2 was obtained, which is almost 2.7 times higher than that of pure CeO2 NFs, revealing that the presence of Au imposed an important influence on the electrocatalytic activity toward CySH. The detailed reasons on such high performance were also discussed. In addition, the as-prepared sensor showed a low detection limit of 10 nM (signal to noise ratio of 3), a wide linear range up to 200 μM for the determination of CySH, an outstanding reproducibility and good long-term stability, as well as an excellent selectivity against common interferents such as tryptophan, tyrosine, methionine, ascorbic acid and uric acid. All these features indicate that the Au/CeO2 composite nanofiber is a promising candidate as a new class of l-cysteine electrocatalyst in the development of highly sensitive and selective CySH electrochemical sensor.

Dual functional rhodium oxide nanocorals enabled sensor for both non-enzymatic glucose and solid-state pH sensing

Both pH-sensitive and glucose-responsive rhodium oxide nanocorals (Rh2O3 NCs) were synthesized through electrospinning followed by high-temperature calcination. The as-prepared Rh2O3 NCs were systematically characterized using various advanced techniques including scanning electron microscopy, X-ray powder diffraction and Raman spectroscopy, and then employed as a dual functional nanomaterial to fabricate a dual sensor for both non-enzymatic glucose sensing and solid-state pH monitoring. The sensing performance of the Rh2O3 NCs based dual sensor toward pH and glucose was evaluated using open circuit potential, cyclic voltammetry and amperometric techniques, respectively. The results show that the as-prepared Rh2O3 NCs not only maintain accurate and reversible pH sensitivity of Rh2O3, but also demonstrate a good electrocatalytic activity toward glucose oxidation in alkaline medium with a sensitivity of 11.46 μA mM-1 cm-2, a limit of detection of 3.1 μM (S/N = 3), and a reasonable selectivity against various interferents in non-enzymatic glucose detection. Its accuracy in determining glucose in human serum samples was further demonstrated. These features indicate that the as-prepared Rh2O3 NCs hold great promise as a dual-functional sensing material in the development of a high-performance sensor forManjakkal both solid-state pH and non-enzymatic glucose sensing.