Entangled Mesh Hydrogels with Macroporous Topologies via Cryogelation for Rapid Atmospheric Water Harvesting.

Sorption-based atmospheric water harvesting (SAWH) is a promising technology to alleviate freshwater scarcity. Recently, hygroscopic salt-hydrogel composites (HSHCs) have emerged as attractive candidates with their high water uptake, versatile designability, and scale-up fabrication. However, achieving high-performance SAWH applications for HSHCs has been challenging because of their sluggish kinetics, attributed to their limited mass transport properties. Herein, a universal network engineering of hydrogels using a cryogelation method is presented, significantly improving the SAWH kinetics of HSHCs. As a result of the entangled mesh confinements formed during cryogelation, a stable macroporous topology is attained and maintained within the obtained entangled-mesh hydrogels (EMHs), leading to significantly enhanced mass transport properties compared to conventional dense hydrogels (CDHs). With it, corresponding hygroscopic EMHs (HEMHs) simultaneously exhibit faster moisture sorption and solar-driven water desorption. Consequently, a rapid-cycling HEMHs-based harvester delivers a practical freshwater production of 2.85 Lwater kgsorbents -1 day-1 via continuous eight sorption/desorption cycles, outperforming other state-of-the-art hydrogel-based sorbents. Significantly, the generalizability of this strategy has been validated by extending it to other hydrogels used in HSHCs. Overall, this work offers a new approach to efficiently address long-standing challenges of sluggish kinetics in current HSHCs, promoting them toward the next-generation SAWH applications. This article is protected by copyright. All rights reserved.

A magnetic resonance conditional robot for lumbar spinal injection: Development and preliminary validation.

PURPOSE: This work presents the design and preliminary validation of a Magnetic Resonance (MR) conditional robot for lumbar injection for the treatment of lower back pain. METHODS: This is a 4-degree-of-freedom (DOF) robot that is 200 × 230 × 130 mm3 in volume and has a mass of 0.8 kg. Its lightweight and compact features allow it to be directly affixed to patient's back, establishing a rigid connection, thus reducing positional errors caused by patient movements during treatment. RESULTS: To validate the positioning accuracy of the needle by the robot, an electromagnetic (EM) tracking system and a needle with an EM sensor embedded in the tip were used for the free space evaluation with position accuracy of 0.88 ± 0.46 mm and phantom mock insertions using the Loop-X CBCT scanner with target position accuracy of 3.62 ± 0.92 mm. CONCLUSION: Preliminary experiments demonstrated that the proposed robot showed improvements and benefits in its rotation range, flexible needle adjustment, and sensor protection compared with previous and existing systems, offering broader clinical applications.

Targeting Compact and Ordered Emitters by Supramolecular Dynamic Interactions for High-performance Organic Ambient Phosphorescence.

Purely organic room-temperature phosphorescence (RTP) materials have received intense attention due to their fascinating optical properties and advanced optoelectronic applications. The promotion of intersystem crossing (ISC) and minimalization of nonradiative dissipation under ambient conditions are key prerequisites for realizing high-performance organic RTP; However, the ISC process is generally inefficient for organic fluorogens and the populated triplet excitons are always too susceptible to be well stabilized by conventional means. Particularly, organizing organic fluorophores into compact and ordered entities by supramolecular dynamic interactions has proven to be a newly-emerged strategy to boost the ISC process greatly and suppress the non-radiative relaxations immensely, facilitating the population and stabilization of triplet excitons to access high-performance organic RTP. Consequently, well-defined organic emitters enable robust RTP emission even in the solution state, thus greatly extending the applications. Here, this review is focused on a timely and brief introduction to recent progress in tailoring ordered high-performance RTP emitters by supramolecular dynamic interactions. Their typical preparation strategies, optoelectronic properties, and applications are thoroughly summarized. In the summary section, key challenges and perspectives of this field are highlighted to suggest potential directions for future study.

Inhibition of pseudorabies virus replication via upregulated interferon response by targeting 7-dehydrocholesterol reductase.

Pseudorabies virus (PRV) is an alpha-herpesvirus capable of infecting a range of animal species, particularly its natural host, pigs, resulting in substantial economic losses for the swine industry. Recent research has shed light on the significant role of cholesterol metabolism in the replication of various viruses. However, the specific role of cholesterol metabolism in PRV infection remains unknown. Here, we demonstrated that the expression of 7-dehydrocholesterol reductase (DHCR7) is upregulated following PRV infection, as evidenced by the proteomic analysis. Subsequently, we showed that DHCR7 plays a crucial role in promoting PRV replication by converting 7-dehydrocholesterol (7-DHC) into cholesterol, leading to increased cellular cholesterol levels. Importantly, DHCR7 inhibits the phosphorylation of interferon regulatory factor 3 (IRF3), resulting in reduced levels of interferon-beta (IFN-ß) and interferon-stimulated genes (ISGs). Finally, we revealed that the DHCR7 inhibitor, trans-1,4-bis(2-chlorobenzylaminomethyl) cyclohexane dihydrochloride (AY9944), significantly suppresses PRV replication both in vitro and in vivo. Taken together, the study has established a connection between cholesterol metabolism and PRV replication, offering novel insights that may guide future approaches to the prevention and treatment of PRV infections.

Pathogenicity and immunogenicity of a quadruple gene-deleted pseudorabies virus variant as a vaccine candidate.

Since late 2011, the PRV variants have emerged in China, characterized by the increased virulence. The traditional attenuated vaccines have proven insufficient in providing complete protection, resulting in substantial economic losses to swine industry. In this study, a vaccine candidate strain, ZJ01-ΔgI/gE/TK/UL21, carrying the quadruple gene deletion was derived from the previously generated three gene-deleted virus ZJ01-ΔgI/gE/TK. As anticipated, piglets inoculated with ZJ01-ΔgI/gE/TK/UL21 exhibited normal body temperatures and showed no viral shedding, consistent with the observations from piglets treated with ZJ01-ΔgI/gE/TK. Importantly, a significant higher level of interferon induction was observed among piglets in the ZJ01-ΔgI/gE/TK/UL21 group compared to those in the ZJ01-ΔgI/gE/TK group. Upon challenge with the PRV variant ZJ01, piglets immunized with ZJ01-ΔgI/gE/TK/UL21 exhibited reduced viral shedding compared to the ZJ01-ΔgI/gE/TK group. Furthermore, piglets vaccinated with ZJ01-ΔgI/gE/TK/UL21 exhibited minimal pathological lesions in brain tissues, similar to those in the ZJ01-ΔgI/gE/TK group. These results underscore the potential of ZJ01-ΔgI/gE/TK/UL21 as a promising vaccine for controlling PRV infection.

Robotic system for magnetic resonance imaging-guided high-intensity focus ultrasound application: Feasibility of breast fibroadenoma treatment.

PURPOSE: This paper presents a high-intensity focus ultrasound (HIFU) robotic system for treating breast fibroadenoma under the guidance of magnetic resonance imaging (MRI). Based on the thermal and mechanical effects of ultrasound, the system aims to deliver ultrasound energy to a target precisely without damaging the normal tissue. The temperature elevation can be monitored in real time by MRI, and the treatment plan can be adjusted during the procedure. The requirements, design specifications, control system and registration of the robotic system are specified. METHODS: The robotic system was designed with a 3 degrees of freedom manipulator with limit switches and encoders, a customised MRI-compatible breast coil, a water bladder with sets of breast-conforming brackets, and a probe capable of generating ultrasound. Twenty volunteers were recruited for this study, and their data were analysed to provide more precise data for the design. The accuracy of the robot was evaluated in free space using a coordinate measuring machine, phantom and ex vivo porcine tissue in MRI room. The study also verified the signal-to-noise ratio (SNR) of the MRI with the effect of the robotic system. RESULTS: The research findings revealed that the manipulator exhibited a translational precision of 0.10 ± 0.14 mm, a rotational fidelity around the X direction of 0.11 ± 0.09°, and an oscillatory exactness around the Y direction of 0.10 ± 0.08°. The investigation of positioning accuracy demonstrated that the robot's error in free space was 0.26 ± 0.07 mm. When subjected to MRI room with agar-silica phantom and ex vivo porcine tissue, the positioning accuracy amounted to 1.11 ± 0.47 mm and 1.57 ± 0.52 mm. In the presence of the robotic system, the SNR of the MRI experienced a 4.2% reduction, which had a negligible impact on image quality. CONCLUSIONS: The conducted experiments validate the efficacy of the proposed MRI-guided HIFU robotic system in executing agar-silica phantom and ex vivo porcine tissue investigations with adequate positioning accuracy. Consequently, this system exhibits certain feasibility for the treatment of breast fibroadenomas.

Tegument protein UL21 of alpha-herpesvirus inhibits the innate immunity by triggering CGAS degradation through TOLLIP-mediated selective autophagy.

Alpha-herpesvirus causes lifelong infections and serious diseases in a wide range of hosts and has developed multiple strategies to counteract the host defense. Here, we demonstrate that the tegument protein UL21 (unique long region 21) in pseudorabies virus (PRV) dampens type I interferon signaling by triggering the degradation of CGAS (cyclic GMP-AMP synthase) through the macroautophagy/autophagy-lysosome pathway. Mechanistically, the UL21 protein scaffolds the E3 ligase UBE3C (ubiquitin protein ligase E3C) to catalyze the K27-linked ubiquitination of CGAS at Lys384, which is recognized by the cargo receptor TOLLIP (toll interacting protein) and degraded in the lysosome. Additionally, we show that the N terminus of UL21 in PRV is dominant in destabilizing CGAS-mediated innate immunity. Moreover, viral tegument protein UL21 in herpes simplex virus type 1 (HSV-1) also displays the conserved inhibitory mechanisms. Furthermore, by using PRV, we demonstrate the roles of UL21 in degrading CGAS to promote viral infection in vivo. Altogether, these findings describe a distinct pathway where alpha-herpesvirus exploits TOLLIP-mediated selective autophagy to evade host antiviral immunity, highlighting a new interface of interplay between the host and DNA virus.Abbreviations: 3-MA: 3-methyladenine; ACTB: actin beta; AHV-1: anatid herpesvirus 1; ATG7: autophagy related 7; ATG13: autophagy related 13; ATG101: autophagy related 101; BHV-1: bovine alphaherpesvirus 1; BNIP3L/Nix: BCL2 interacting protein 3 like; CALCOCO2/NDP52: calcium binding and coiled-coil domain 2; CCDC50: coiled-coil domain containing 50; CCT2: chaperonin containing TCP1 subunit 2; CGAS: cyclic GMP-AMP synthase; CHV-2: cercopithecine herpesvirus 2; co-IP: co-immunoprecipitation; CQ: chloroquine; CRISPR: clustered regulatory interspaced short palindromic repeat; Cas9: CRISPR-associated system 9; CTD: C-terminal domain; Ctrl: control; DAPI: 4',6-diamidino-2-phenylindole; DBD: N-terminal DNA binding domain; DMSO: dimethyl sulfoxide; DYNLRB1: dynein light chain roadblock-type 1; EHV-1: equine herpesvirus 1; gB: glycoprotein B; GFP: green fluorescent protein; H&E: hematoxylin and eosin; HSV-1: herpes simplex virus 1; HSV-2: herpes simplex virus 2; IB: immunoblotting; IRF3: interferon regulatory factor 3; lenti: lentivirus; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MARCHF9: membrane associated ring-CH-type finger 9; MG132: cbz-leu-leu-leucinal; NBR1: NBR1 autophagy cargo receptor; NC: negative control; NEDD4L: NEDD4 like E3 ubiquitin protein ligase; NH4Cl: ammonium chloride; OPTN: optineurin; p-: phosphorylated; PFU: plaque-forming unit; Poly(dA:dT): Poly(deoxyadenylic-deoxythymidylic) acid; PPP1: protein phosphatase 1; PRV: pseudorabies virus; RB1CC1/FIP200: RB1 inducible coiled-coil 1; RNF126: ring finger protein 126; RT-PCR: real-time polymerase chain reaction; sgRNA: single guide RNA; siRNA: small interfering RNA; SQSTM1/p62: sequestosome 1; STING1: stimulator of interferon response cGAMP interactor 1; TBK1: TANK binding kinase 1; TOLLIP: toll interacting protein; TRIM33: tripartite motif containing 33; UL16: unique long region 16; UL21: unique long region 21; UL54: unique long region 54; Ub: ubiquitin; UBE3C: ubiquitin protein ligase E3C; ULK1: unc-51 like autophagy activating kinase 1; Vec: vector; VSV: vesicular stomatitis virus; VZV: varicella-zoster virus; WCL: whole-cell lysate; WT: wild-type; Z-VAD: carbobenzoxy-valyl-alanyl-aspartyl-[O-methyl]-fluoromethylketone.

A dinoflagellate-inspired mechanochromic film for fast and reversible information encryption and display.

Inspired by dinoflagellates, we developed a flexible film consisting of spiropyran-based soft polyacrylate and Zn(OTf)2. The open-ring form of spiropyran coordinated with Zn(OTf)2 under stretching to produce a visible fluorescent color change from colorless to yellow. The potential of this film was demonstrated for fast and reversible information encryption and decryption.

Atmospheric Hygroscopic Ionogels with Dynamically Stable Cooling Interfaces Enable a Durable Thermoelectric Performance Enhancement.

In thermoelectric generator (TEG) systems, heat dissipation from their cold sides is an accessible, low-cost, and effective way to increase the temperature gap for their thermoelectric performance enhancement. Although significant efforts have been dedicated mediated by hygroscopic hydrogel coolers as self-sustained alternatives for effective heat removal, it still remains a challenge for overcoming instabilities in their cooling process. The inevitable mechanical deformation of these conventional hydrogels induced by excessive water desorption may cause a detached cooling interface with the targeted substrates, leading to undesirable cooling failure. Herein, a self-sustained and durable evaporative cooling approach for TEG enabled by atmospheric hygroscopic ionogels (RIGs) with stable interfaces to efficiently improve its thermoelectric performance is proposed. Owing to its superior hygroscopicity, the RIGs can achieve higher heat dissipation for TEG through water evaporation than that of common commercial metal heat sinks. Moreover, its favorable adhesion enables the RIG closely interact with the TEG surface either in static or dynamic conditions for a durable thermoelectric performance enhancement. It is believed that such a self-sustained evaporative cooling strategy based on the RIG will have great implications for the enhancement of TEG's efficiency, demonstrating a great promise in intermittent thermal-energy utilizations.

[Correlation analysis of color change and Maillard reaction during processing of Gardeniae Fructus Praeparatus].

The chromaticity space parameters of the samples during the processing of Gardeniae Fructus Praeparatus(Jiaozhizi in Chinese herbal name, JZZ) were measured by the visual analyzer to analyze the color variation rule during the processing of JZZ, and the content changes of total reducing sugar, total amino acid and 5-hydroxymethylfurfural(5-HMF) related to Maillard reaction were measured. Pearson correlation analysis and linear regression analysis of the data were carried out by SPSS 24.0 software. The experimental results showed that the objective coloration of the samples in the processing of JZZ was basically consistent with the traditional subjective color judgment; the contents of total reducing sugar and total amino acids showed a decreasing trend during the processing of JZZ, and the content of 5-HMF showed an increasing trend, which was in line with Maillard reaction law. Pearson correlation analysis results showed that there was a significant correlation between the chromaticity space parameters L~*(lightness value), a~*(red green value), b~*(yellow blue value), E~*ab(total color value) and the contents of total reducing sugar, total amino acid and 5-HMF(P<0.01), among which the values of L~*, a~*, b~*, E~*ab were positively correlated with the contents of total reducing sugar and total amino acid, and negatively correlated with the contents of 5-HMF. The results of linear regression analysis also showed that these two were highly correlated. In this study, by establishing the correspondence relationship between the color change of JZZ processing and Maillard reactants, wecan not only provide a basis for the objective digital expression of subjective color of JZZ, but also provide a reference for explaining the processing mechanism of JZZ from a new perspective.

Treatment Mechanism of Gardeniae Fructus and Its Carbonized Product Against Ethanol-Induced Gastric Lesions in Rats.

Gardeniae Fructus (GF) and carbonized GF (GFC) have been shown to exert a gastrointestinal protective effect and are frequently used in clinical practice for the treatment of hemorrhage and brown stool. In this study, we employed a combination of pharmacological methods and metabolomics in a rat model of ethanol-induced acute stomach ulcer to investigate the gastroprotective effect of GF and GFC water extracts and the potential mechanism involved in this process. The levels of nitric oxide (NO) and interleukin 6 (IL-6) in the plasma of rats were determined. The results showed that both GF and GFC reduced the ethanol-induced gastric lesions and expression of NO and IL-6 in these rats. Of note, 16 and 11 feature metabolites were filtered and identified in the GF and GFC groups, respectively. Both GF and GFC act by restoring the biosynthesis of valine, leucine, and isoleucine, and the metabolism of glycerophospholipids. Moreover, histological evaluation revealed that heat processing of GF to create GFC enhanced the gastric mucosa protective effect. Furthermore, heat processing converted the main pathway from alanine, aspartate, and glutamate metabolism, associated with GF, to histidine metabolism, associated with GFC. GF and GFC ameliorated gastric mucosa lesions in rats via reductions in NO production and inflammatory cytokine secretion, and the induction of prostaglandin E2.

[Study on quality standard of rice as excipients during rice stir-frying method].

Commercially available japonica rice and indica rice with different trade names were collected,and then based on the method of rice stir-frying,their many indexes were evaluated,for example the physical and chemical properties such as appearance color,grain type,broken kernel ratio,length-width ratio,1 000-grain weight,specific heat capacity,moisture content,amylose content,and protein content. The discriminant function analysis was used to determine the effective factors affecting the quality of rice as excipients. The results showed that two types of rice could be distinguished by rice color parameter a*,grain parameter circularity,1 000-grain weight and amylose content. These four effective factors can be used as the quality evaluation indexes for fried rice as excipients.Protein is one of the main components of rice,and its content affects the quality of rice. There is a significant difference in the protein content between japonica rice and indica rice. Therefore,protein content should be used as one of the evaluation indexes for rice quality. After comprehensive consideration,it is suggested that the red-green value a*shall not be less than 0. 50; the circularity not less than 53. 0,the 1 000-grain weight not less than 16. 0 g,the amylose content not less than 12. 0% and the protein content not less than4. 0% in the japonica rice; the red-green value a*shall not be lower than-1. 0,the circularity not less than 41. 0,the 1 000-grain weight not less than 13. 0 g,the amylose content not less than 9. 0% and the protein content not less than 3. 5% in the indica rice. In this study,the quality evaluation standards for rice as excipients( japonica rice,indica rice) were supplemented and improved,laying foundation for the development of quality standards for rice as excipients with the rice stir-frying method.

[Establishment of extraction method for Gardeniae Fructus extract and its application in evaluating different Gardeniae Fructus decoction pieces].

In this experiment,the gradation analysis method was used to evaluate the quality of different pieces of Gardeniae Fructus through the extraction rate difference and the difference analysis of the main components in the extract. In this experiment cold-dip and hot-dip methods were used to compare the yield of Gardeniae Fructus extract and the content of chemical constituents with water,25%,50%,75% and 95% ethanol fractions. By weighted calculation,the optimal extraction method of Gardeniae Fructus was determined,and this was verified by practical application. RESULTS:: showed that for the water-soluble extract,cold dip method was better than the hot dip method; and for alcohol-soluble extract,75% ethanol under cold dip method was best. The verification results showed that water-soluble extracts under cold dip methods could be used to significantly distinguish the raw Gardeniae Fructus( GF) and processed( stir-baked) GF( GFP) collected from the market. Meanwhile,this method could be also used to distinguish the same batch of GF,GFP and carbonized GF( GFC) with significant differences,respectively( P<0. 05). Ethanol-soluble extract can be used to clearly distinguish GFP and GFC pieces in the same batch( P<0. 05). The results of content determination showed that the variation coefficient of components in GF processed products was higher than that in extracts,and the content of hydroxygeniposide was the most significant component between GF and its processed products. It is suggested that the method of water-soluble extract of GF and the determination of the content of gardoside should be combined together to evaluate the quality of GF and its heat processed products.

Fabrication of composite microneedles integrated with insulin-loaded CaCO3 microparticles and PVP for transdermal delivery in diabetic rats.

Dissolving microneedles (MNs) display high efficiency, safety and painless in transdermal delivery for poorly permeable drugs. Here, a dissolving composite MNs prepared from insulin-loaded CaCO3 microparticles (INS-CaCO3 MPs) and poly(vinyl pyrrolidone) (PVP) as matrix were fabricated with two-step centrifuging and molding process to immobilize insulin in the MNs. The as-prepared INS-CaCO3/PVP MNs exhibited remarkable mechanical strength and slower solubility properties when compared with pure PVP MNs. In vitro skin insertion capability was determined by staining with FITC-labeled insulin which was revealed after insertion, gradually diffusing from the puncture sites to deeper tissues. In vivo pharmacodynamic studies were then conducted to estimate the feasibility of the administration of insulin-loaded dissolving MNs on diabetic rats for glucose regulation. The relative pharmacological availability (RPA) and relative bioavailability (RBA) of insulin from MNs were 98.2 and 96.6%. Thus, this study suggests that the use of INS-CaCO3/PVP MNs achieved both high efficiency and constant release of insulin in comparison with the traditional subcutaneous injection approach and presented a promising device to delivery insulin for diabetic therapy.

Microneedles fabricated from alginate and maltose for transdermal delivery of insulin on diabetic rats.

To reduce the inconvenient and painful of subcutaneous needle injection, the calcium ion cross-linked alginate/maltose (Ca2+/Alg-Mal) composite microneedles have been fabricated by a template method. The as-prepared microneedles exhibited strong mechanical properties with the highest failure force around 0.41N/needle. The biological activity and stability of loaded insulin in microneedles were investigated. Due to the good mechanical properties and excellent biocompatibility, the as-prepared microneedles have been applied for transdermal delivery of insulin on diabetic Sprague-Dawley (SD) rat models in vivo. After transdermal administration to the diabetic rats, the released insulin from biodegradable composite microneedles exhibit an obvious and effective hypoglycemic effect with relative pharmacological availability (RPA) and relative bioavailability (RBA) at 94.1±5.6% and 93.7±4.7% compared with that of subcutaneous injection route. This work suggests that as-prepared Ca2+/Alg-Mal microneedles can be used to encapsulate insulin and have a potential application in diabetes treatment via transdermal ingestion.

Separable Microneedles for Near-Infrared Light-Triggered Transdermal Delivery of Metformin in Diabetic Rats.

Near-infrared (NIR) light-triggered and separable segmented microneedles (MNs), consisting of lauric acid and polycaprolactone (LA/PCL) arrowheads and poly(vinyl alcohol) and polycaprolactone (PVA/PVP) supporting bases, have been fabricated. A hypoglycemic drug (metformin) and photothermal conversion factor (Cu7S4 nanoparticles) are encapsulated into LA/PCL arrowheads. Due to the dissolution of soluble supporting bases after the absorption of tissue fluid, the separable MNs arrowheads can be embedded into skin after insertion. Under the NIR-light irradiation, the LA/PCL arrowheads exhibit an excellent thermal-ablation change with a low amount of Cu7S4 nanoparticles (0.1 wt %) due to the low melting point of LA and PCL, thus enabling the release behavior of the encapsulated model drug to be photothermally triggered. Compared to the hypodermic injection of metformin, the thermal ablation of separable MNs triggered by NIR irradiation in the current research exhibit an excellent hypoglycemic effect in vivo. It suggests that the NIR-induced thermal-ablation MNs comprise a prospective transdermal drug-delivery system for the precise control of the timing and dosage of a drug that is dependent on NIR administration.

Microneedles Integrated with ZnO Quantum-Dot-Capped Mesoporous Bioactive Glasses for Glucose-Mediated Insulin Delivery.

A self-responsive insulin delivery system is highly desirable because of its high sensitivity dependent on blood glucose levels. Herein, a smart pH-triggered and glucose-mediated transdermal delivery system, insulin-loaded and ZnO quantum dots (ZnO QDs) capped mesoporous bioactive glasses (MBGs) integrated with microneedles (MNs), was developed to achieve control and painless administration. ZnO QDs as a promise pH-responsive switch were employed to cap the nanopores of MBGs via electrostatic interaction. The drug (insulin) and glucose-responsive factor (glucose oxidase/catalase, GOx/CAT) were sealed into the pores of MBGs. GOx/CAT in the MBGs could catalyze glucose to form gluconic acid, resulting decrease in the local pH. The ZnO QDs on the surface of the MBGs could be dissolved in the acidic condition, leading to disassembly of the pH-sensitive MBGs and then release of preloaded insulin from the MBGs. As a result of administration in a diabetic model, an excellent hypoglycemic effect and lower hypoglycemia risk were obtained. These results indicate that as-prepared pH-triggered and glucose-mediated transdermal delivery systems have hopeful applications in the treatment of diabetes.

Fabrication of Dissolving Microneedles with Thermal-Responsive Coating for NIR-Triggered Transdermal Delivery of Metformin on Diabetic Rats.

This study described near-infrared (NIR) light-responsive polymer-nanodot composite microneedles (MNs) used for on-demand transdermal drug delivery. Bismuth (Bi) nanodots stabilized by poly(vinylpyrrolidone) (PVP) as a photothermal conversion agent and metformin as an antidiabetic drug were introduced into the dissolving MNs coated with lauric acid (LA). When the MNs were irradiated with NIR light, light-to-heat transduction induced by the Bi nanodots caused the LA to melt. As a result, the polymer matrix was dissolved after absorbing the interstitial fluid, enabling the encapsulated metformin release from the MNs into skin tissue. Compared with subcutaneous injection of metformin, the administration using the Bi nanodots-induced NIR responsive MNs developed in the current research exhibited a remarkable hypoglycemic effect in vivo. This work indicates that the as-fabricated Bi nanodot-induced NIR responsive and LA-coated MNs have potential applications in diabetes treatment. Additionally, these artificial MNs also present a promising platform for delivering other therapeutic drugs.

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.