Microfluidic Preparation and Evaluation of Multivesicular Liposomes Containing Gastrodin for Oral Delivery across the Blood-Brain Barrier.

In this study, multivesicular liposomes (MVLs) were prepared by microfluidic technology and used for delivering gastrodin (GAS), a water-soluble drug, across the blood-brain barrier (BBB). The formulations and preparation parameters in preparing gastrodin multivesicular liposomes (GAS-MVLs) were both optimized. Some properties of GAS-MVLs including morphology, particle size, encapsulation efficiency, and in vitro release were evaluated. An in vitro BBB model was established by coculturing mouse brain endothelial cells (bEnd.3) and astrocytes (C8-D1A). The permeability of GAS-MVLs across the BBB model was evaluated. Finally, the permeability of GAS-MVLs across BBB was evaluated by in vivo pharmacokinetics in mice. The concentrations of GAS in the blood and brain were determined by high-performance liquid chromatography (HPLC), and then brain-targeting efficiency (BTE), relative uptake rate (Re), and peak concentration ratio (Ce) were calculated. The results showed that, using a Y-type microfluidic chip and setting the flow rate ratio of the second aqueous phase to the W/O emulsion phase at 23, with a total flow rate of 0.184 m/s, the prepared GAS-MVLs showed an obvious multivesicular structure and a relatively narrow distribution of particle sizes. The prepared GAS-MVLs were spherical with a dense structure. The average particle size was 2.09 ± 0.17 µm. The average encapsulation rate was (34.47 ± 0.39)%. The particle size of MVLs prepared by the microfluidic method was much smaller than that prepared by the traditional method, which was usually larger than 10 µm. After 6 h from the beginning of the administration, the apparent transmittance of GAS-MVLs in the in vitro BBB model was 67.71%, which was 1.92 times higher than that of the GAS solution. In vivo pharmacokinetic study showed that the intracerebral area under curve (AUC) of GAS-MVLs was 5.68 times higher than that of the GAS solution, and the e peak concentration (Cmax) was 2.036 times higher than that of the GAS solution. BTE was 1.945, intracerebral Re was 5.688, and Ce was 2.036. Both in vitro and in vivo experiment results showed that GAS-MVLs prepared by microfluidic technology in this study significantly delivered GAS across BBB and enriched GAS in the brain. It provides a possibility for brain-targeting delivery of GAS in the prevention and treatment of central nervous system diseases by oral administration and lays the foundation for further development of oral brain-targeted preparations of GAS.

Quercetin nanocrystals prepared using a microfluidic chip with improved in vitro dissolution.

OBJECTIVE: In order to improve the dissolution property of quercetin (QCT), the quercetin nanocrystals (QNCs) were prepared in this study. METHODS: QNCs were prepared by a 100 µm diameter Y-shape microfluidic channel. Some impact factors affecting the generation of QNCs such as concentration and flow rate were investigated. Furthermore, the fluid mixing in the microfluidic channel was simulated by fluid software. RESULTS: XRPD and DSC analyses indicated that the prepared QNCs were amorphous. Stable QNCs with a particle size of 77.9 ± 3.63 nm and polydispersity index of 0.26 ± 0.02 were obtained. TEM showed that the as-prepared QNCs had a uniform spherical shape with an average particle size of about 100-300 nm. In the dissolution medium without cosolvent Tween -80, the dissolution of QCT was poor, its final accumulated dissolution was only 3.95%, while that of QNCs was 66%. CONCLUSION: When QCT was changed to QNCs by microfluidic technology, its dissolution property could be obviously improved. Therefore, microfluidic technology as a new method to prepare nanocrystals has a good applying prospect in improving dissolution property for poorly water-soluble drugs.

Bilayer nanofibrous wound dressing prepared by electrospinning containing gallic acid and quercetin with improved biocompatibility, antibacterial, and antioxidant effects.

OBJECTEIVES: The purpose of this study was to prepare an antibacterial, antioxidant, and biocompatible bilayer nanofibrous wound dressing by using electrospinning. METHODS: The micromorphology and bilayer structure characteristics of the GA-Qe-PVP-PCL nanofibers were analyzed by SEM. The physicochemical characteristics were analyzed by XRD and FTIR. The uptake, mechanical properties, water contact angle, water vapor transmission and in vitro drug release were evaluated. In addition, the effect of antibacterial, antioxidant and biocompatability of the nanofibers were evaluated, respectively. RESULTS: The SEM results showed that the GA-Qe-PVP-PCL nanofibers had a smooth surface, no beading phenomenon, and a prominent bilayer structure. The diameter and porosity of the drug-loading layer and waterproof support layer of the nanofibers were 842 ± 302 nm, 242 ± 50 nm, and 88.56 ± 1.67%, 94.49 ± 1.57%, respectively. Moreover, the water uptake, mechanical properties, water contact angle, and water vapor transmission showed ideal performance. The results of in vitro drug release indicated that GA and Qe were both released rapidly, which was conducive to accelerating wound healing. The GA-Qe-PVP-PCL nanofibers exhibited antibacterial effects against both bacteria as well as high antioxidant activity. Additionally, the GA-Qe-PVP-PCL nanofibers possessed good compatibility, could promote the proliferation, adhesion, and migration of L929 fibroblast cells. CONCLUSION: The nanofibers we developed met the requirements of ideal materials for wound dressing, which makes the nanofibers the potential to be a wound dressing for wound care.

Chitosan/Polylactic Acid Nanofibers Containing Astragaloside IV as a New Biodegradable Wound Dressing for Wound Healing.

The ideal wound dressing should adequately protect the wound from bacterial infection and provide a suitable healing environment for the wound. Thus, we prepared a biodegradable functional nanofiber dressing with good antibacterial and biocompatibility by electrospinning technology. The average diameter of the dressing was 354 ± 185 nm, and the porosity was 93.27%. Scanning electron microscopy (SEM) showed that the dressing was smooth without beading. It was also characterized by Fourier-transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD). The wettability and water vapor permeability of the dressing were tested; the results showed that the dressing had good wettability and permeability. The ability of drug release indicates that continuous release over a period of time is beneficial to wound healing. Finally, the antibacterial effect and in vivo pharmacodynamic evaluation of AS/CS/PLA nanofiber dressing were studied; the result showed that it had significant antibacterial activity and the ability to promote wound healing.

A separable double-layer self-pumping dressing containing astragaloside for promoting wound healing.

Some skin wounds often have many exudate. Ordinary single layer electrospunning nanofiber wound dressings often don't have enough capacity to absorb them. Therefore, a separable double layer electrospunning nanofiber dressing was developed in this work. The dressing had a separable feature that allowed the upper layer to be separated and removed after it had absorbed a significant amount of wound exudate. This dressing consisted of an upper layer of super hydrophilic sodium polyacrylate nanofibers and a bottom layer of 3D-structure coaxial nanofibers with encapsulated Astragaloside (AS). The results showed that nanofibers had better morphology. The water absorption rate, water vapor transmission rate and free radical scavenging rate of the double-layer dressings were 1461.71 ± 39.72 %, 1193.63 ± 134 g·m-2·day-1, and 63.35 ± 3.65 %, respectively. The double-layer nanofiber dressing achieved 65.69 ± 2.62 % and 75.10 ± 6.26 % inhibition against Staphylococcus aureus and Escherichia coli, respectively. The double-layer dressing had proliferative, migratory, and adhesive effects on L929 fibroblasts. And the double-layer dressing resulted in a 96.78 ± 1.0 % wound healing rate in rats after giving a 14 days treatment. Therefore, the 3D-structure separable double-layer wound dressing designed and prepared in this study was effective in promoting wound healing.

Lifting Triplet Energy and Bipolar Characteristics by Limiting the Rotation of the Peripheral Groups in Host Materials to Achieve High-Efficiency Blue OLED.

Bipolar host materials with high triplet energy are of great significance for highly efficient blue organic light-emitting diodes (OLEDs). In this work, three donor-acceptor-donor (D-A-D) type host materials with identical non-rigid diphenylsulfone center but differing in rotation degree of peripheral amino substituted derivatives from rotating freely diphenylamine (SODP) to rotating partially iminodibenzyl (SOId) and rotating restricted carbazole (SOCz) were designed and synthesized. It was demonstrated that the triplet energy (ET ) level of the materials promoted by limiting the rotation degree of the peripheral groups, which was 2.72 eV for SODP, 2.73 eV for SOId and 2.78 eV for SOCz, respectively. Besides, the results of the single-carrier devices indicate SOCz possess better bipolar characteristic. Using FIrpic as guest emitter, the blue OLED with SOCz as host material exhibited superior device performance with a low turn-on voltage of 3.3 V, a maximum current efficiency (CE) of 30.1 cd A-1 , a maximum power efficiency (PE) of 32.2 lm W-1 , and a maximum external quantum efficiency (EQE) of 14.0%. This work provides a beneficial guideline for realizing promising host materials in efficient blue OLEDs.

Modulation for efficiency and spectra of non-doped white organic light emitting diodes by combining an exciplex with an ultrathin phosphorescent emitter.

Herein, structured non-doped white organic light-emitting diodes (WOLEDs) were designed by combining the emission of a blue exciplex and orange-red phosphorescent ultrathin layer. The device efficiency and spectra were modulated successfully by adjusting the thickness of the exciplex layer and ultrathin layer, respectively. Meanwhile, high efficiency with external quantum efficiency (EQE) ranging from 15% to 22%, power efficiency from 33 lm W-1 to 47 lm W-1 and warm white emission with correlated color temperature (CCT) from 1600 K to 2600 K were realized. The energy transfer process and emission mechanism is also discussed, and the results reveal that the efficient charge trapping and recombination contribute to the improvement of device efficiency and reduce the roll-off efficiency.