Weijiang Yu

Electrospun carbon nanofibers coated with urchin-like ZnCo2O4 nanosheets as a flexible electrode material

Electrospun carbon nanofiber composites (ZnCo2O4/Ag–GO–CNFs) coated with 3D urchin-like ZnCo2O4 nanosheets to form a shish-kebab structure have been prepared using a combination of electrospinning, carbonization and hydrothermal treatments. The composition and microstructure of ZnCo2O4/Ag–GO–CNFs were investigated using field emission scanning electron microscopy (FE-SEM), X-ray photoelectron spectroscopy (XPS), transmission electron microscopy (TEM), X-ray diffraction (XRD) and Brunauer–Emmett–Teller (BET) analysis. Interestingly, ZnCo2O4/Ag–GO–CNFs provided a new style of electrode materials and exhibited an excellent specific capacity of 459.48 mA h g−1 at 20 mV s−1. Notably, the specific capacity of ZnCo2O4/Ag–GO–CNFs also exhibited a remarkable cycling stability (96.0% retention after 9000 cycles), which holds great promise for practical applications in energy storage devices as a carbon-based electrode material.

Preparation of chitosan-based multifunctional nanocarriers overcoming multiple barriers for oral delivery of insulin.

To overcome multiple barriers for oral delivery of insulin, the chitosan-based multifunctional nanocarriers modified by L-valine (LV, used as a target ligand to facilitate the absorption of the small intestine) and phenylboronic acid (PBA, used as a glucose-responsive unit) have been designed and evaluated in this study. The resultant nanocarriers exhibited low cytotoxicity against HT-29 cells and excellent stability against protein solution. The insulin release behaviors were evaluated triggered by pH and glucose in vitro. The chemical stability of loaded insulin against digestive enzyme were established in presence of simulated gastric fluid (SGF) containing pepsin and simulated intestinal fluid (SIF) containing pancreatin, respectively. The uptake behavior of HT-29 cells was evaluated by confocal laser scanning microscope. After oral administration to the diabetic rats, an effective hypoglycemic effect was obtained compared with subcutaneous injection of insulin. This work suggests that L-valine modified chitosan-based multifunctional nanocarriers may be a promising drug delivery carrier for oral administration of insulin.

A composite hydrogel system containing glucose-responsive nanocarriers for oral delivery of insulin.

Development of an oral delivery strategy for insulin therapeutics has drawn much attention in recent years. In this study, a glucose-responsive nanocarriers for loading of insulin has been prepared firstly. The resultant nanocarriers exhibited relative low cytotoxicity against Caco-2 cells and excellent stability against protein solution. The insulin release behaviors were evaluated triggered by pH and glucose in vitro. In order to enhance the oral bioavailability of insulin, the insulin-loaded glucose-responsive nanocarriers were further encapsulated into a three-dimensional (3D) hyaluronic acid (HA) hydrogel environment for overcoming multiple barriers and providing multi-protection for insulin during the transport process. The hypoglycemic effect for oral delivery of insulin was studied in vivo. After oral administration to the diabetic rats, the released insulin from hydrogel systems containing insulin-loaded glucose-responsive nanocarriers exhibited an effective hypoglycemic effect for longer time compared with insulin-loaded nanocarriers.

Fabrication of biodegradable composite microneedles based on calcium sulfate and gelatin for transdermal delivery of insulin

To reduce the inconvenience and pain of subcutaneous needle injection, the calcium sulfate and gelatin biodegradable composite microneedle patches with high aspect-ratio microneedles (MNs) and a flexible substrate have been developed. The microneedles with an aspect-ratio approximate 6:1 exhibit excellent mechanical property which can achieve 0.4N for each needle. The cross-section views show the inside of microneedles that have abundant pores and channels which offer potential for different drug-release profiles. The preparation procedures, degradable property for the biodegradable composite microneedle patches are described in the paper. Insulin, the drug to control blood glucose levels in diabetic patients, has been embedded into the biodegradable composite MNs. The hypoglycemic effect for transdermal delivery of insulin is studied using diabetic Sprague-Dawley (SD) rats as models in vivo. After transdermal administration to the diabetic rats, the released insulin from biodegradable composite MNs exhibit an obvious and effective hypoglycemic effect for longer time compared with that of subcutaneous injection route. This work suggests that biodegradable composite MNs containing of insulin have a potential application in diabetes treatment via transdermal ingestion.

Transdermal delivery of insulin with bioceramic composite microneedles fabricated by gelatin and hydroxyapatite

The organic-inorganic bioceramic composite microneedles (MNs) were prepared from hydroxyapatite (Hap) and gelatin (Gel) via a template method. The resultant hydroxyapatite and gelatin composite MNs exhibited low cytotoxicity and excellent mechanical properties. After transdermal administration to the diabetic rats, the insulin could be released from bioceramic composite MNs. An obvious and effective hypoglycemic effect could be obtained compared with that of subcutaneous injection route. This work suggests that bioceramic composite MNs containing of insulin have a potential application in diabetes treatment via transdermal ingestion.

Polymer microneedles fabricated from alginate and hyaluronate for transdermal delivery of insulin

To reduce the inconvenient and painful of subcutaneous needle injection, the polymer microneedle patches that fabricated from modified alginate and hyaluronate were prepared for transdermal delivery of insulin. The as-prepared microneedles (MNs) exhibited excellent mechanical strength to penetrate the skin and good degradability to release loaded insulin. In vitro skin insertion capability was determined by staining with tissue-marking dye after insertion, and the real-time penetration depth was monitored using optical coherence tomography. Confocal microscopy images revealed that the rhodamine B and fluorescein isothiocyanate-labeled insulin (FITC-insulin) can gradually diffuse from the puncture sites to deeper tissue. In vivo and pharmacodynamic studies were then conducted to estimate the feasibility of the administration of insulin-loaded microneedle patches on diabetic mice for glucose regulation. The relative pharmacologic availability (RPA) and relative bioavailability (RBA) of insulin from microneedle patches were 90.5±6.8% and 92.9±7%, respectively. These results suggests the MNs developed in this study have a promising application in diabetes treatment via transdermal delivery.

Preparation of poly(lactic-co-glycolic acid) and chitosan composite nanocarriers via electrostatic self assembly for oral delivery of insulin

To improve insulin bioavailability and overcome multiple barriers for oral delivery of insulin, the composite nanocarriers (PLGA/FA-CS) prepared from poly(lactide-co-glycoside) (PLGA) and folic acid modified chitosan (FA-CS) were fabricated via electrostatic self-assembly method. The resultant composite nanocarriers exhibited low cytotoxicity against HT-29 cells and excellent stability against protein solution. The chemical stability of loaded insulin against digestive enzyme were established in presence of simulated gastric fluid (SGF) containing pepsin and simulated intestinal fluid (SIF) containing pancreatin, respectively. The uptake behavior of HT-29 cells was evaluated by confocal laser scanning microscope. After oral administration to the diabetic rats, an effective hypoglycemic effect was obtained compared with subcutaneous injection of insulin. This work suggests that the as-prepared composite nanocarriers may be a promising drug delivery system for oral administration of insulin and other biomacromolecules.

H2O2-Responsive mesoporous silica nanoparticles integrated with microneedle patches for the glucose-monitored transdermal delivery of insulin

A glucose-mediated insulin delivery system would be highly satisfactory for diabetes diagnosis dependent on the concentration of blood glucose in the body. Herein, a novel microneedle (MN) delivery device integrated with insulin-loaded and H2O2-responsive mesoporous silica nanoparticles (MSNs) was designed to achieve fast and painless administration. The MSNs were obtained by the modification by 4-(imidazoyl carbamate)phenylboronic acid pinacol ester (ICBE) and following a host-guest complexation between ICBE and α-cyclodextrin (α-CD). A drug and a glucose-responsive factor, namely insulin and glucose oxidase (GOx), were encapsulated into the MSNs. GOx in the MSNs could convert glucose to gluconic acid and generate hydrogen peroxide (H2O2). The phenylboronic ester on the surface of the MSNs could be oxidized in the presence of H2O2, which resulted in the destruction of host-guest complexation, leading to the disassembly of the drug-loaded MSNs and subsequent release of the preloaded insulin. After transdermal administration to diabetic rats, an effective hypoglycemic effect was obtained by detection over time compared with that of subcutaneous injection. This work suggests that the as-prepared glucose-mediated and H2O2-responsive MN systems have promising applications in diabetes treatment.

Surfactant-Mediated Crystallization-Driven Self-Assembly of Crystalline/Ionic Complexed Block Copolymers in Aqueous Solution

A series of crystalline/ionic complexed block copolymers (BCPs) with various compositions have been prepared by sequential reactions. The BCPs with different hydrophilic fractions can self-assemble into various morphologies, such as spindlelike, rodlike, and spherical micelles with different crystallinity of the core. Bis(2-ethylhexyl) sulfosuccinate sodium salt (AOT) is added as a surfactant to induce the morphological transition of BCPs in aqueous media. The introduced AOT can be tightly bound to the cationic units, and a water-insoluble unit in the corona forms, leading to a reduced tethering density. Consequently, morphological variety changing from rods to platelets to fibril to dendrite-like micelles can be observed.

Near-infrared light triggered and separable microneedles for transdermal delivery of metformin in diabetic rats

Near-infrared light triggered and separable microneedles (MNs) were fabricated by a unique molding method. The photothermal conversion agent (Prussian blue nanoparticles, PB NPs) and hypoglycemic drug (metformin) were embedded into the separable polycaprolactone (PCL) MNs arrowheads. These MNs arrowheads were capped on dissolving polyvinyl alcohol/polyvinyl pyrrolidone (PVA/PVP) solid supporting substrate. The as-fabricated MNs exhibited excellent photothermal conversion properties under near-infrared light (NIR) irradiation, causing the MNs arrowheads to melt due to the photothermal conversion of PB NPs. After applying on skin, the separable MNs arrowheads could be embedded in the skin due to the dissolution of supporting substrates after absorbing the interstitial fluid. When the embedded MNs arrowheads were exposed to NIR irradiation, the MNs arrowheads underwent a rapid thermal ablation from a solid to a liquid state, thus enabling the release of encapsulated metformin to be NIR modulated. They allowed on-demand control of timing and dose of the drug released. This suggests that the developed NIR-triggered and separable MNs are a promising transdermal drug delivery system that enables the patient or physician to adjust therapy precisely in an active manner, thus improving treatment efficiency and reducing side-effects.