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Drug Delivery and Translational Research · 2023 · IF 5.4

A topical thermosensitive hydrogel system with cyclosporine A PEG-PCL micelles alleviates ulcerative colitis induced by TNBS in mice

Xiao Chuyao,Li Genyun,Li Xiaoyue,Wang Dan,Wu Ya,Sun Minghui,Huang Jiangeng,Si Luqin

Ulcerative colitis (UC) is an idiopathic, chronic, relapsing disease. In most cases, only the distal colon is affected, and the colonic stasis or fast colonic transit through the inflamed colon usually results in reduced exposure of the distal inflamed colon. Although the immunosuppressant cyclosporine A (CsA) has been used in patients with severe colitis who do not respond to corticosteroids, the clinical application of CsA remains limited due to the systemic toxicities and insufficient accumulation at the site of action for the intravenous and oral routes. In this study, we loaded CsA into the amphipathic poly(ethylene glycol)-poly(ε-caprolactone) (PEG-PCL) micelles and then embedded them in hydrogels consisting of chitosan, poloxamer 188, and poloxamer 407 to construct a thermosensitive and mucoadhesive hydrogel drug delivery system (PLCP). The PLCP presented a high drug-loading capacity and showed a stable and rapid gelation rate after rectal administration into the body. Compared to CsA-loaded micelles and Sandimmun (Neoral ® ), the developed thermosensitive gel exhibited prolonged retention on the inflamed colon, as seen from in vitro adhesion and in vivo distribution experiments. It also fast mitigated colitis symptoms in TNBS-treated mice by regulating the expression levels of proinflammatory cytokines (TNF-α, IL-1β, COX-2, and iNOS2), anti-inflammatory cytokines (IL-10, Nrf2, NQO1, and HO-1), and other relevant biochemical factors. Our results suggested that CsA-loaded micelle thermal hydrogel system could be a promising strategy by enhancing the retention in the diseased colon and promoting the relief and recovery of UC. Graphical Abstract

CAS / MDL: 9003-11-6
研究领域: 药剂学 · 药理学 · 药物递送系统 · 炎症性肠病
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JOURNAL OF CONTROLLED RELEASE · 2016 · IF 7.441

Targeted delivery of low-dose dexamethasone using PCL–PEG micelles for effective treatment of rheumatoid arthritis

Qin Wang,Jiayu Jiang,Wenfei Chen,Hao Jiang,Zhirong Zhang,Xun Sun

Glucocorticoid (GC) is the cornerstone therapy of rheumatoid arthritis , but high doses are associated with serious adverse effects. In an effort to improve the efficacy of low-dose GC therapy, we developed a micelle system for targeted delivery to inflamed joints and validated the approach in a rat model of arthritis. Micelles loaded with dexamethasone (Dex) self-assembled from the amphipathic poly (ethylene glycol)-block–poly (ε­caprolactone) (PCL–PEG) polymer via film dispersion, and they were injected intravenously at a dose of only 0.8   mg/kg into rats with adjuvant-induced arthritis. The micelles persisted for a relatively long time in the circulation, and they accumulated preferentially in inflamed joints. Micelle-delivered Dex potently reduced joint swelling, bone erosion, and inflammatory cytokine expression in both joint tissue and serum. PCL–PEG micelles caused only moderate adverse effects on body weight, lymphocyte count and blood glucose concentration, and they weakly activated the host complement system. These results suggest that encapsulating Dex in PCL–PEG micelles may allow for safe and effective low-dose GC therapy targeting inflammatory disorders.

CAS / MDL: 7693-46-1
研究领域: 药理学 · 风湿病学 · 纳米技术 · 炎症
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Tissue Engineering and Regenerative Medicine · 2023 · IF 3.6

MiRNA320a Inhibitor-Loaded PLGA-PLL-PEG Nanoparticles Contribute to Bone Regeneration in Trauma-Induced Osteonecrosis Model of the Femoral Head

Zhang Ying,Li Chuan,Wei Qiushi,Yuan Qiang,He Wei,Zhang Ning,Dong Yiping,Jing Zhenhao,Zhang Leilei,Wang Haibin,Cao Xiangyang

BACKGROUND: This study aimed to explore the effect of a nanomaterial-based miR-320a inhibitor sustained release system in trauma-induced osteonecrosis of the femoral head (TIONFH). METHODS: The miR-320a inhibitor-loaded polyethylene glycol (PEG)- Poly(lactic-co-glycolic acid) (PLGA)- Poly-L-lysine (PLL) nanoparticles were constructed using the double emulsion method. The TIONFH rabbit model was established to observe the effects of miR-320a inhibitor nanoparticles in vivo . Hematoxylin–eosin staining and microcomputed tomography scanning were used for bone morphology analysis. Bone marrow mesenchymal stem cells (BMSCs), derived from TIONFH rabbits, were used for in vitro experiments. Cell viability was determined using the MTT assay. RESULTS: High expression of miR-320a inhibited the osteogenic differentiation capacity of BMSCs in vitro by inhibiting the expression of the osteoblastic differentiation markers ALP and RUNX2. MiR-320a inhibitor-loaded PEG-PLGA-PLL nanoparticles were constructed with a mean loading efficiency of 1.414 ± 0.160%, and a mean encapsulation efficiency of 93.45 ± 1.24%, which released 50% of the loaded miR-320a inhibitor at day 12 and 80% on day 18. Then, inhibitor release entered the plateau. After treatment with the miR-320a inhibitor nanoparticle, the empty lacunae were decreased in the femoral head tissue of TIONFH rabbits, and the osteoblast surface/bone surface (Ob.S/BS), osteoblast number/bone perimeter (Ob.N/B.Pm), bone volume fraction, and bone mineral density increased. Additionally, the expression of osteogenic markers RUNX2 and ALP was significantly elevated in the TIONFH rabbit model. CONCLUSION: The miR-320a inhibitor-loaded PEG-PLGA-PLL nanoparticle sustained drug release system significantly contributed to bone regeneration in the TIONFH rabbit model, which might be a promising strategy for the treatment of TIONFH.

CAS / MDL: 50-02-2 50-81-7
研究领域: 纳米技术 · 骨科 · 再生医学 · 分子生物学
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Biomed Research International · 2018 · IF 2.583

Green and Efficient PEG-Based Ultrasonic-Assisted Extraction of Polysaccharides from Tree Peony Pods and the Evaluation of Their Antioxidant Activity In Vitro

Xiaonan Zhang,Qingfeng Ban,Xibo Wang,Zhongjiang Wang

We adopted and developed an ultrasonic-assisted extraction method to obtain polysaccharides from tree peony pods using polyethylene glycol (PEG) as the solvent. The technological parameters have been designed as a single factor to enhance the tree peony pod polysaccharide extraction yield. Specific conditions (ultrasound irradiation power, 250 W; ultrasound irradiation time, 30 min; reaction temperature 50°C; liquid-solid ratio, 25 mL/g; and concentration of PEG, 0.2 g/mL) generated an experimental yield of 14.14% 0.44%. Subsequently, the monosaccharide composition of the tree peony pod polysaccharides was determined by HPLC using a 1-phenyl-3-methyl-5-pyrazolone precolumn derivatization method. The results indicated that tree peony pod polysaccharides contained mannoses, rhamnose, glucuronic acid, galacturonic acid, glucose, galactose, arabinose, and fucose with a molar ratio of 1.44 : 2.87 : 0.32 : 18.99 : 3.99 : 10.21 : 0.96 : 1.85 : 0.21. The tree peony pod polysaccharides obtained are mainly galacturonic acid and galactose, which are acidic polysaccharides. Finally, the antioxidant activities (DPPH and FRAP) of the tree peony pod polysaccharides were assessed, and the compounds exhibited moderate antioxidant activities.

研究领域: 食品科学 · 药学 · 生物化学 · 植物化学
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DRUG DELIVERY · 2018 · IF 3.095

Curcumin-loaded PLGA-PEG nanoparticles conjugated with B6 peptide for potential use in Alzheimer’s disease

Shengnuo Fan,Yuqiu Zheng,Xuan Liu,Wenli Fang,Xiaoyu Chen,Wang Liao,Xiuna Jing,Ming Lei,Enxiang Tao,Qiulan Ma,Xingmei Zhang,Rui Guo,Jun Liu

Alzheimer’s disease is a neurodegenerative disorder mainly characterized by β-amyloid deposit and tau hyperphosphorylation with no curative treatments. Curcumin (Cur) has been proved to have potential use in Alzheimer’s disease with its anti-amyloid, anti-inflammatory, and anti-oxidant properties, etc. However, its hydrophobicity and low bioavailability hinder its application. In this paper, we designed a novel brain-target nanoparticle, poly(lactide-co-glycolide)-block-poly(ethylene glycol) (PLGA-PEG) conjugated with B6 peptide and was loaded with Cur (PLGA-PEG-B6/Cur) and administered it into HT22 cells and APP/PS1 Al transgenic mice. The in vitro assays including dynamic light scattering (DLS), flow cytometry (FCM), red blood cell (RBC) lysis, and thromboelastography (TEG) analysis indicated that this nanoparticle could narrow the diameter of Cur, increase its cellular uptake and possess good blood compatibility. The results from Morris water maze proved that PLGA-PEG-B6/Cur could tremendously improve the spatial learning and memory capability of APP/PS1 mice, compared with native Cur. The ex vivo assays including Bielschowsky silver staining, immunostaining, and western blotting demonstrated that PLGA-PEG-B6/Cur could reduce hippocampal β-amyloid formation and deposit and tau hyperphosphorylation. Thus, we suggested that PLGA-PEG-B6/Cur nanoparticles would be of potential and promising use for the treatment of Alzheimer’s disease.

研究领域: 神经科学 · 药学 · 纳米技术 · 神经退行性疾病
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BIOMACROMOLECULES · 2024 · IF 5.5

POSS and PEG Contained Copolymer for Antibioadhesive Rigid Contact Lenses Materials Application

Lin Liang,Yulin Hu,Yueze Hong,Zhihui Wu,Hao Chen,Quankui Lin

Myopia is a global public health issue. Rigid contact lenses (RCLs) are an effective way to correct or control myopia. However, bioadhesion issues remain one of the significant obstacles limiting its clinical application. Although enhancing hydrophilicity through various surface treatments can mitigate this problem, the duration of effectiveness is short-lived and the processing involved is complex and costly. Herein, an antiadhesive RCLs material was designed via 8-armed methacrylate-POSS (8MA-POSS), and poly(ethylene glycol) methacrylate (PEGMA) copolymerization with 3-[tris(trimethylsiloxy)silyl] propyl methacrylate (TRIS). The POSS and PEG segments incorporated P(TRIS-co-PEGMA-co-8MA-POSS) (PTPM) material was obtained and their optical transparency, refractive index, resolution, hardness, surface charge, thermal features, and wettability were tested and optimized. The antibioadhesion activities, including protein, lipid, and bacteria, were evaluated as well. In vitro and in vivo results indicated that the optimized antibioadhesive PTPM materials present good biocompatibility and biosafety. Thus, such POSS and PEG segments containing material were a potential antibioadhesive RCL material option.

CAS / MDL: 78-67-1
研究领域: 材料科学 · 聚合物化学 · 眼科学 · 生物医学工程
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LANGMUIR · 2024 · IF 3.7

Selectivity of PEG/Salt Aqueous Two-Phase System Enhanced by Surfactant@MWCNT Composites

Chunyang Liu,Yanrong Cheng,Delan Ge,Ju Xie,Xia Guo

Aqueous two-phase systems (ATPS) are considered a new type of green separation system, but their low selectivity to target molecules limits their practical application. In this study, we used surfactant@MWCNT as an adjuvant to improve the selectivity of PEG/(NH4)2SO4 ATPS. The surfactants used include Triton X-100 (TX-100), Tween 80, sodium dodecyl sulfate (SDS), sodium dodecyl benzenesulfonate (SDBS), and bis(2-ethylhexyl)sulfosuccinate sodium salt (AOT). Nine aromatic compounds, including syringic acid, vanillin, tryptophan, phenylalanine, tyrosine, mandelic acid, theophylline, theobromine, and cephalexin, were selected as model extracts. The results showed that the use of the surfactant@MWCNT composite as an adjuvant significantly improved the selectivity of the ATPS toward syringic acid among the nine extracts. Moreover, the selectivity of the ATPS for syringic acid with the TX-100/MWCNT composite as the adjuvant is better than that with the Tween 80/MWCNT composite as the adjuvant, followed by that with the anionic surfactant/MWCNT composite as the adjuvant. The enhanced selectivity of ATPS by the surfactant/MWCNT composite is ascribed to the spatial effect and the electrostatic and hydrophobic interactions between the extract and the surfactant adsorbed on the MWCNT.

研究领域: 化学工程 · 分离科学 · 纳米技术 · 环境科学
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Materials Science & Engineering C-Materials for Biological Applications · 2016 · IF 3.42

A composited PEG-silk hydrogel combining with polymeric particles delivering rhBMP-2 for bone regeneration

Dakun Ma,Gang An,Min Liang,Yugang Liu,Bin Zhang,Yansong Wang

Given the fabulous potential of promoting bone regeneration, BMP-2 has been investigated widely in the bone tissue engineering field. A sophisticated biomaterial loaded with BMP-2, which could avoid the required supraphysiological dose leading to high medical costs and risks of complications, has been considered as a promising strategy to treat non-healing bone defects. In this study, we developed a simple approach to engineer a composited hydrogel consisting polymeric particles (PLA/PLGA) used as a BMP-2 delivery vehicle. Compared with other groups, the introduction of PLA into PEG-silk gels endowed the hydrogel new physicochemical characteristics especially hydrophobicity which inhibited the burst release of BMP-2 and enhanced gel's structural stability. Moreover, such composited gels could stabilize entrapped proteins and maintain their bioactivity fully in vitro. In vivo, the bio-degradability experiment demonstrated this system was biocompatible and the reinforced hydrophobicity significantly decreased degradation rate, and in rat critical-sized cranial defects model, the gel containing PLA promoted the most bone formation. These findings demonstrated the introduction of PLA changed physicochemical features of gels more suitable as a BMP-2 carrier indicated by inducing bone regeneration efficiently in large bone defects at low delivered dose and this system may own translational potential.

CAS / MDL: 25322-68-3
研究领域: 生物医学工程 · 组织工程 · 材料科学 · 骨科
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Nanoscale · 2016 ·Vol. 8 ·期 20 ·10832-10842 · IF 7.76

“Sheddable” PEG-lipid to balance the contradiction of PEGylation between long circulation and poor uptake

Caiyan Zhao,Hongzhang Deng,Jing Xu,Shuyi Li,Lin Zhong,Leihou Shao,Yan Wu,Xing-jie Liang

PEGylated lipids confer longer systemic circulation and tumor accumulation via the enhanced permeability and retention (EPR) effect. However, PEGylation inhibits cellular uptake and subsequent endosomal escape. In order to balance the contradiction between the advantages of long circulation and the disadvantages of poor uptake of PEGylated lipids, we prepared a “sheddable” PEG-lipid micelle system based on the conjugation of PEG and phosphatidyl ethanolamine (DSPE) with a pH sensitive benzoic imine bond. In a physiological environment, the PEG-protected micelles were not readily taken up by the reticuloendothelial system (RES) and could be successfully delivered to tumor tissue by the EPR effect. In a tumor acidic microenvironment, the PEG chains detached from the surfaces of the micelles while the degree of linker cleavage could not cause a significant particle size change, which facilitated the carrier binding to tumor cells and improved the cellular uptake. Subsequently, the “sheddable” PEG-lipid micelles easily internalized into cells and the increased acidity in the lysosomes further promoted drug release. Thus, this “sheddable” PEG-lipid nanocarrier could be a good candidate for effective intracellular drug delivery in cancer chemotherapy.

CAS / MDL: 75-89-8
研究领域: 药剂学 · 纳米技术 · 肿瘤学 · 药物递送系统
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Gels · 2024 ·Vol. 10 ·期 4 ·278 · IF 5

In Vitro Antibacterial and Anti-Inflammatory Properties of Imidazolium Poly(ionic liquids) Microspheres Loaded in GelMA-PEG Hydrogels

Chao Zhou,Mengdi Sun,Danni Wang,Mingmei Yang,Jia Ling Celestine Loh,Yawen Xu,Ruzhi Zhang

Repairing damaged tissue caused by bacterial infection poses a significant challenge. Traditional antibacterial hydrogels typically incorporate various components such as metal antimicrobials, inorganic antimicrobials, organic antimicrobials, and more. However, drawbacks such as the emergence of multi-drug resistance to antibiotics, the low antibacterial efficacy of natural agents, and the potential cytotoxicity associated with metal antibacterial nanoparticles in hydrogels hindered their broader clinical application. In this study, we successfully developed imidazolium poly(ionic liquids) (PILs) polymer microspheres (APMs) through emulsion polymerization. These APMs exhibited notable antibacterial effectiveness and demonstrated minimal cell toxicity. Subsequently, we integrated the APMs into a gelatin methacryloyl (GelMA)—polyethylene glycol (PEG) hydrogel. This composite hydrogel not only showcased strong antibacterial and anti-inflammatory properties but also facilitated the migration of human skin fibroblasts (HSF) and human umbilical vein endothelial cells (HUVECs) and promoted osteogenic differentiation in vitro.

研究领域: 组织工程 · 生物医用材料 · 抗菌研究 · 细胞生物学
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ACS Applied Materials & Interfaces · 2016 · IF 7.145

A Multifunctional PB@mSiO2–PEG/DOX Nanoplatform for Combined Photothermal–Chemotherapy of Tumor

Yun Yan Su,Zhaogang Teng,Hui Yao,Shou Ju Wang,Ying Tian,Yun Lei Zhang,Wen Fei Liu,Wei Tian,Li Juan Zheng,Nan Lu,Qian Qian Ni,Xiao Dan Su,Yu Xia Tang,Jing Sun,Ying Liu,Jiang Wu,Gui Fen Yang,Guang Ming Lu,Long Jiang Zhang

In this work, we design mesoporous silica-coated Prussian blue nanocubes with PEGyltation to construct multifunctional PB@mSiO2–PEG nanocubes. The PB@mSiO2–PEG nanocubes have good biocompatibility, excellent photothermal transformation capacity, in vivo magnetic resonance and photoacoustic imaging ability. After loading antitumor drug doxorubicin (DOX) in the PB@mSiO2–PEG nanocubes, the constructured PB@mSiO2–PEG/DOX nanoplatforms show an excellent pH-responsive drug release character within 48 h, namely, an ultralow cumulative drug release amount of 3.1% at pH 7.4 and a high release amount of 46.6% at pH 5.0. Upon near-infrared laser irradiation, the PB@mSiO2–PEG/DOX nanoplatforms show an enhanced synergistic photothermal and chemical therapeutic efficacy for breast cancer than solo photothermal therapy or chemotherapy.

研究领域: 纳米技术 · 生物医学工程 · 癌症研究 · 药物递送系统 · 材料科学
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Journal of Materials Chemistry B · 2017 ·Vol. 5 ·期 22 ·4121-4127 · IF 4.543

Injectable self-healing hydrogels formed via thiol/disulfide exchange of thiol functionalized F127 and dithiolane modified PEG

Hansen Yu,Yanan Wang,Haiyang Yang,Kang Peng,Xingyuan Zhang

Injectable self-healing hydrogels have found broad applications in drug delivery, tissue engineering and controlled 3D cell culture. Recently, cyclic disulfides were found to be useful in cross-linking and stabilizing liposomes by disulfide exchange polymerization, benefiting from the enhanced reactivity of the disulfide bonds. Herein, we report an injectable self-healing hydrogel constructed from cross-linked F127 with thermo and pH dual responsivity. The rapid sol–gel transition ability at body temperature allows it to be used as an injectable hydrogel. And the increased reactivity of the disulfides of cyclic dithiolane due to the ring tension makes the hydrogel self-heal under not only alkaline conditions but also neutral or even mildly acidic conditions.

研究领域: 材料科学 · 生物材料 · 药物递送 · 组织工程
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