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Advanced Healthcare Materials · 2024 · IF 10

Magneto-Thermal Hydrogel Swarms for Targeted Lesion Sealing

Ziheng Chen,Hui Chen,Kaiwen Fang,Na Liu,Jiangfan Yu

Magnetic microswarms capable of performing navigation to targeted lesions show great potential for in vivo medical applications. However, using the swarms for lesion cavity filling encounters challenges from precise delivery and sealing. Herein, this work develops a magneto-thermal hydrogel swarm consisting of magnetic hydrogel particles, which can perform phase transition induced by temperature change. The particles are prepared using a temperature-responsive hydrogel matrix, tissue adhesive monomers, and magnetic microparticles. The swarms can be remolded to various shapes, and it can be used to seal perforation in phantom and gastric tissue. The swarms can also serve as drug carriers, and their drug release profiles induced by temperature changes are characterized. Finally, the targeted delivery, adaptive filling, and sealing of a gastric ulcer using the swarms are achieved in ex vivo and in vivo environments.

研究领域: 生物医学工程 · 材料科学 · 医疗机器人 · 组织工程
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INTERNATIONAL JOURNAL OF PHARMACEUTICS · 2019 · IF 4.213

Self-assembled hexagonal liquid crystalline gels as novel ocular formulation with enhanced topical delivery of pilocarpine nitrate

Xingqi Wang,Yong Zhang,Jie Huang,Mengqiu Xia,Liu Liu,Chunling Tian,Rongfeng Hu,Shuangying Gui,Xiaoqin Chu

The aim of this paper was to develop hexagonal liquid crystalline (H II ) gels that can be used as a novel ocular delivery system for pilocarpine nitrate (PN). H II gels were prepared by a vortex method using phytantriol/triglyceride/water (71.15: 3.85: 26, w/w) ternary system. The gels were characterized by crossed polarized light microscopy, small-angle X-ray scattering, differential scanning calorimetry and rheology. And, in vitro drug release behavior and ex vivo corneal permeation were investigated. Finally, preocular residence time evaluation, eye irritation test, histological examination and miotic tests were studied in vivo and compared with carbopol gel. Based on various characterization techniques, the inner structure of the gels were H II mesophase and exhibited a pseudoplastic fluid behaviour. In vitro release results revealed that PN could be released continuously from H II gel over a period of 24 h. The ex vivo apparent permeability coefficient of H II gel was 3.15-fold (P < 0.01) higher than that of the Carbopol gel. Compared with Carbopol gel, H II gel displayed longer residence time on the eyeballs surface using fluorescent labeling technology. Furthermore, the H II gel caused no ocular irritation was estimated by corneal hydration levels, Draize test and histological inspection. Additionally, in vivo miotic study showed that H II gel had a remarkably long-lasting decrease in the pupil diameter of rabbits. In conclusion, H II gels would be a promising sustained-release formulation for ocular drug delivery.

研究领域: 药剂学 · 药物递送系统 · 眼科学
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Nano Today · 2023 · IF 17.4

A supramolecular gel with unique rheological properties for treating corneal virus infection

Jingjing Hu,Xujiao Zhou,Sijia Chen,Di Yin,Yuhan Yang,Minjie Chen,Chunyi Gui,Yujia Cai,Jiaxu Hong,Yiyun Cheng

Herpes simplex keratitis (HSK) caused by herpes simplex virus-1 infection of the cornea has taken a significant toll on the visual health of people worldwide. Anti-viral hydrogels are preferred in the treatment of HSK due to enhanced topical drug retention and reduced side effects, however, current polymer-based gelling systems usually generate clumpy or uneven gel layers on ocular surface, and are easily cleared by eyelid blinking. This study proposes a supramolecular gel co-assembled by all-small-molecule building blocks including ganciclovir and 2′-deoxyguanosine in the presence of potassium ions . The developed gel performs fascinating rheological and texture properties including high viscoelastic, good spread ability, and deformation recovery behavior, enabling the formation of a uniform and thin gel layer on ocular surface to resist the clearance by eyelid blinking and tear washing. The gel shows similar ocular convenience, but much longer drug retention in ocular tissues and higher therapeutic efficacy compared to the clinical ganciclovir gel on the primary and recurrent mouse HSK models, rabbit HSK models, and also efficiently inhibited the HSV-1 replication in ex vivo human corneal tissues . The results suggest that this all-small-molecule supramolecular gel could be a promising drug formulation for treating HSK. Data and materials availability The main data supporting the results in this study are available within the paper and its Supplementary Information . The associated raw data and analyzed datasets are too large to be readily shared publicly, but they are available from the corresponding author on reasonable request.

CAS / MDL: 7220-79-3 61-73-4
研究领域: 药剂学 · 病毒学 · 眼科学 · 材料科学
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STAR Protocols · 2023 · IF 0

Protocol for screening α-synuclein PET tracer candidates in vitro and ex vivo

Jie Xiang,Yiyuan Xia,Shilin Luo,Zhentao Zhang,Keqiang Ye

Summary Alpha-synuclein (α-Syn) positron emission tomography (PET) imaging is a valuable approach for diagnosing and monitoring synucleinopathies-related diseases, such as Parkinson disease. Here, we present a protocol for screening potential α-Syn PET tracers using in vitro and ex vivo approaches. We describe steps for employing recombinant pre-formed fibrils and conducting screening procedures on neuronal models, mouse models, and patients’ brain tissue sections to assess the specificity and selectivity of the candidate compounds. For complete details on the use and execution of this protocol, please refer to Xiang et al. (2023). 1

研究领域: 神经科学 · 分子生物学 · 医学成像 · 诊断
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Journal of Materials Chemistry B · 2021 ·Vol. 9 ·期 47 ·9770-9783 · IF 6.331

A honokiol-mediated robust coating for blood-contacting devices with anti-inflammatory, antibacterial and antithrombotic properties

Linhua Li,Chong Chen,Chunle Zhang,Rifang Luo,Xiaorong Lan,Fan Guo,Liang Ma,Ping Fu,Yunbing Wang

Thrombus, bacterial infections, and severe inflammation are still serious problems that have to be faced with blood-contacting materials. However, it is a great challenge to simultaneously meet the above functional requirements in a simple, economical and efficient method. As such, we put forward a robust and versatile coating strategy by covalently modifying the multi-pharmacological drug honokiol (HK) with an amine-rich polydopamine/polyethyleneimine coating, through which anticoagulant, antibacterial and anti-inflammatory properties were obtained (DPHc) simultaneously. The amine content in the DPHc coating was lower than the detection limit, while it contained abundant phenolic hydroxyl groups (49 μmol cm−2). Meanwhile, the 30 day drug release test confirmed that the drug was firmly modified on the surface of the coating without release. A systematic in vitro and ex vivo evaluation confirmed that the coating had significant anti-thrombotic properties. The antibacterial rates of the DPHc coating against Staphylococcus aureus and Escherichia coli reached 99.98% and 99.99%, respectively. In addition, subcutaneous implantation indicated that the DPHc coating also has excellent histocompatibility. To the best of our knowledge, this is the first study using HK as a coating material that can not only combat thrombosis and infection but also significantly inhibit inflammation associated with the use of blood-contacting materials, thus expanding the application of HK in the field of biomaterials.

CAS / MDL: 1310-73-2 67-66-3
研究领域: 生物材料 · 药学 · 生物医学工程
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Frontiers in Microbiology · 2019 · IF 4.259

Nematophin, an Antimicrobial Dipeptide Compound From Xenorhabdus nematophila YL001 as a Potent Biopesticide for Rhizoctonia solani Control

Zhang Shujing,Liu Qi,Han Yunfei,Han Jinghua,Yan Zhiqiang,Wang Yonghong,Zhang Xing

This study was conducted to purify and identify metabolites of antimicrobial activity against phytopathogens from Xenorhabdus nematophila YL001. Three dipeptide compounds were purified from its cell-free cultural broth and identified as (±)-nematophin, cyclo (L-Pro-Gly), and N, N′-dimethyl-cyclo (L-Phe-L-Leu). Nematophin demonstrated a wider antifungal spectrum than the other two compounds. It also exhibited strong inhibitory effects on mycelial growth of Rhizoctonia solani and Phytophthora infestans with EC50 values of 40.00 and 51.25 μg/ml, respectively. Its (S)-configuration structure [(+)-nematophin] was also synthesized and exhibited higher antimicrobial activity than the enantiomeric mixture. The detached leaf assay revealed that nematophin possessed significant preventive and curative efficacy against R. solani on broad bean leaves showing corresponding control efficacies of 93.01 and 94.93% at 1,000 μg/ml, comparable to those of a chemical fungicide (carbendazim) at 500 μg/ml. Additionally, the pot experiments indicated that nematophin could effectively inhibit the disease extension on rice and broad bean plants caused by R. solani. Nematophin also exerted some adverse influences on the sclerotial development of R. solani by dramatically suppressing their formation and maturation at 40.00 μg/ml, as well as their germination at 15.00 μg/ml. Morphological and ultrastructural observations showed that the hyphae of R. solani became twisted, shriveled, and deformed at the growing points after exposure to nematophin at 40.00 μg/ml, and that the subcellular fractions also became abnormal concurrently, especially the mitochondrial structure. These results indicate that nematophin has great potential to be used as a bio-pesticide in agricultural production.

研究领域: 农业科学 · 微生物学 · 植物病理学 · 生物技术
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JOURNAL OF FOOD ENGINEERING · 2024 · IF 5.3

Curcumin-loaded microcapsules with soy and whey protein as wall material: In vitro release, and ex vivo absorption based on the rat small intestine

Luping Wang,Peng Wu,Zejun Hu,Yiqing Chen,Xia Jin,Ruoxuan Deng,Timothy V. Kirk,Xiao Dong Chen

Plant proteins, serving as an environmentally friendly and cost-effective alternative to animal proteins, have gained widespread usage in encapsulating various bioactive compounds like curcumin. However, understanding how plant protein-based microcapsules compare to those made with animal proteins in terms of disintegration, release, and absorption in the gastrointestinal tract (GIT) remains limited. This study aims to investigate the impact of soy protein isolate (SPI) and whey protein isolate (WPI) as wall materials on the release, stability, and absorption of curcumin. Spray-dried SPI-based microcapsules (SPI–C) exhibited significantly lower encapsulation efficiency (77.1%) and loading efficiency (3.6%) compared to WPI-based microcapsules (WPI–C) (97.6% and 9.6%, respectively). Structural analysis revealed pleated hollow spherical structures for SPI-C and a concave surface with a single-chamber structure for WPI-C. SPI-C demonstrated higher proteolysis (55.8% vs . 44.1%) during in vitro digestion, leading to greater curcumin release ratio (67.9% vs . 59.2%) and digestive stability (97.9% vs . 93.7%) compared to WPI-C. Notably, SPI-C exhibited higher apparent permeability (0.97 × 10 −6  cm/s) to the ex vivo rat small intestine than WPI-C (0.44 × 10 −6  cm/s). These findings suggest improved gastrointestinal stability and absorption of curcumin encapsulated by SPI, indicating the potential for enhanced utilization of plant-derived proteins in encapsulating bioactive compounds.

CAS / MDL: 10035-06-0 56-45-1
研究领域: 食品科学 · 药学 · 生物技术
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ACS Applied Materials & Interfaces · 2019 · IF 8.456

Self-Nanoemulsifying Electrospun Fiber Enhancing Drug Permeation

Yi Xiang,Jing Liang,Lili Liu,Fei Wang,Lianfu Deng,Wenguo Cui

Electrospun fibers are excellent drug carriers and tissue engineering scaffolds. However, approaches to promote drug permeation in tissues with such carriers remain of great interest. Here, we propose a Quality-by-Design strategy to enhance drug permeation with self-nanoemulsifying electrospun fibers. Owing to the nanoemulsion which formed spontaneously when the polymer contacts aqueous solution such as body fluid, the resulting drug-laden fibrous membrane exhibits an outstanding drug permeation and therapeutic enhancement effect in a Franz cell experiment with ex vivo abdomen skin of rats, an artificial connective tissue model, and an in vivo rheumatoid arthritis model in rats. Meanwhile, the material also shows the capacity of rational regulation on the rate of drug release. These features of the present strategy establish our material as a new efficient approach for various clinical conditions calling for cure.

研究领域: 药剂学 · 药物递送系统 · 组织工程 · 材料科学
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RARE METALS · 2023 ·Vol. 43 ·期 3 ·1263-1274 · IF 8.8

Stark splitting of intense red emission for Er3+ in Oh symmetry sites realizing optical temperature sensing in biological applications

Guo Yue,Qin Lin-Jun,Xu Jing,Jiang Xiao-Ping,Yue Xiao-Yu,Hou Yi,Shi Hao,Wang Li-Xi,Zhang Qi-Tu

Optical temperature sensing based on the fluorescence intensity ratio (FIR) of red emission for lanthanide ions holds significant relevance in non-contact temperature measurement for biological application. In this study, the perovskite-structured KZnF 3 is utilized as a host material for Er 3+ to achieve a high-purity upconversion (UC) red emission. The observed Stark splitting of the red emission peak provides evidence of the energy level splitting of Er 3+ . Group theory is employed to decompose the spectral branching of Er 3+ under the point group symmetry of KZnF 3 , allowing for the derivation of Stark splitting energy levels induced by the crystal field effect. The optical temperature-sensing behavior of the red UC luminescence was investigated, specifically examining the FIR of the splitting sub-peaks, which exhibited an exponential relationship with temperature. The KZnF 3 : Yb 3+ , Er 3+ demonstrated a relative sensitivity ( S r ) of 0.00182%·K −1 at 298 K, highlighting its excellent response to temperature. Ex vivo bio-thermometry experiments conducted on chicken breast validated the material's ability to penetrate biological tissues and showed its significant sensitivity of the FIR to temperature. These results establish KZnF 3 :Yb 3+ , Er 3+ as a promising material for optical thermometry in various biological applications. Graphic abstract

研究领域: 光学传感 · 材料科学 · 发光测温学 · 生物光子学 · 固态物理学
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ACS Biomaterials Science & Engineering · 2020 · IF 4.152

A Hybrid Genipin-Cross-Linked Hydrogel/Nanostructured Lipid Carrier for Ocular Drug Delivery: Cellular, ex Vivo, and in Vivo Evaluation

Yibin Yu,Shuo Xu,Shihui Yu,Jinyu Li,Guoxin Tan,Sanming Li,Weisan Pan

We developed a hybrid nanostructured lipid carrier/dual pH- and thermo-sensitive hydrogel (NLC-Gel) for ocular delivery of quercetin (QN). The hydrogel consisted of carboxymethyl chitosan and poloxamer 407 (P407) was cross-linked using a naturally occurring cross-linker genipin (GP), while the hydrogel cross-linked using glutaraldehyde was used as a control. NLC loaded with quercetin/hydrogel cross-linked by a genipin hybrid drug delivery system (QN-NLC-Gel-GP) exhibited better cytocompatibility and lower ocular irritation than its glutaraldehyde counterpart. The levels of cellular uptake in NLC and NLC-Gel groups were improved. The results of fluorescence imaging and ex vivo transcorneal study indicated that NLC could facilitate transcorneal penetration of lipophilic molecules and incorporation into the hydrogel could increase the precorneal residence time of NLC. The area under the curve of quercetin in the NLC-Gel group was 4.4-fold that in the Eye drops group because of a longer precorneal retention time. In summary, the developed drug delivery system has enormous potential for ophthalmic applications.

CAS / MDL: 38215-36-0
研究领域: 药学 · 材料科学 · 眼科学 · 药物递送系统
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ACS Applied Materials & Interfaces · 2024 · IF 8.3

Ultrasound-Responsive Hydrogel Incorporated with TGF-β Mimetic Peptides for Endometrium Recovery to Restore Fertility

Jinlong Qin,Min Sun,Jiajing Cheng,Huici Jiang,Mingchen Lv,Jianxing Jing,Ran Chen,Zhen Fan,Jianzhong Du

Unavoidable damage to the basal layer of the endometrium has a huge negative impact on a woman’s reproductive health and menstrual cycle. However, it is difficult for medicine to penetrate a series of biological barriers toward the basal layer in the deeper area of the endometrium. To meet this challenge, we developed an ultrasound-responsive hydrogel incorporated with a transforming growth factor-beta (TGF-β) mimetic peptide to enhance pregnancy outcomes by restoring the function of a wounded endometrium due to its deep-tissue-penetration capability. In vitro studies revealed that the TGF-β-mimetic-peptide-loaded hydrogel could achieve 64.35% of cell migration under ultrasound stimulation even in phosphate-buffered saline of pH 6.0. Upon in situ sonication at the uterus, carboxymethyl chitosan can be released from degraded hydrogel to open tight junctions with reduced interstitial pressure by ultrasound to promote deep penetration. Rat studies revealed that the penetration capability of TGF-β-mimetic-peptide-loaded hydrogel with sonication was 1.6 times higher than that of the control group. Besides the rat uterine model, ex vivo human uterine tissue was also collected and imaged, demonstrating up to ∼700 μm of tissue penetration depth. In addition, compared to control groups, effective uterus recovery without intrauterine stenosis and endometrial cavity fluid was observed from rats with severe uterine injury treated by TGF-β-mimetic-peptide-loaded hydrogel. In addition, fertility restoration in the endometrial injury model was observed after treatment with such an ultrasound-responsive hydrogel incorporated with TGF-β mimetic peptides. Overall, this work provides an effective approach to treating endometrial injury for enhanced pregnancy outcomes.

研究领域: 生物医学工程 · 生殖医学 · 组织工程 · 药学
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Agronomy-Basel · 2025 ·Vol. 15 ·期 9 ·2211 · IF 3.4

Induction and Enlargement of Bulblets in Lilium brownii var. viridulum In Vitro

Zheng Zhang,Jingfang Wei,Leifeng Xu,Jun Ming,Panpan Yang

Lilium browniivar.viridulumis a popular natural health product that combines medicine and food. However, the lack of high-quality and efficient propagation technology has been a significant impediment to the development of theL. browniivar.viridulumindustry. In this study, bulb scales ofL. browniivar.viridulumwere used as materials to investigate the induction of bulblets from scales, as well as the proliferation and enlargement of the induced bulblets. An in vitro regeneration system forL. browniivar.viridulumwas successfully established. The most effective methods for scale disinfection were found to be 75% alcohol disinfection for 30 s and 10% Sodium Hypochlorite (NaClO) disinfection for 15 min. The recommended medium for scale differentiation was Murashige and Skoog (MS) + 0.05 mg·L−11-Naphthaleneacetic acid (NAA) + 0.25 mg·L−1Thidiazuron (TDZ) + 0.05 mg·L−1kinetin (KIN) + 30 g·L−1sucrose + 6 g·L−1Activated Charcoal (AC). The recommended medium for bulblet proliferation was MS + 1.5 mg·L−16-benzylaminopurine (6-BA) + 0.5 mg·L−1NAA + 30 g·L−1sucrose. The recommended medium for bulblet enlargement was Modified MS Medium (potassium dihydrogen phosphate (KH2PO4, KDP) doubled) + 90 g·L−1sucrose. Bulblets with diameters of 1.5 cm were transplanted, and the germination rate was 100%. This study established a systematic in vitro regeneration system forL. browniivar.viridulum, which will provide the foundation for industrial production ofL. browniivar.viridulumbulbs and improvement through genetic transformation.

CAS / MDL: 86-87-3
研究领域: 植物学 · 植物组织培养 · 园艺学 · 植物繁殖 · 生物技术
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