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sustained-release
MOLECULES · 2021 ·Vol. 26 ·期 16 ·4982 · IF 4.412

Sustained-Release Solid Dispersion of High-Melting-Point and Insoluble Resveratrol Prepared through Hot Melt Extrusion to Improve Its Solubility and Bioavailability

Wenjing Zhu,Wenling Fan,Xiaotong Zhang,Meiqi Gao

This study aimed to prepare a sustained-release solid dispersion of poorly water-soluble resveratrol (RES) with high melting point in a single hot melt extrusion step. A hydrophobic–hydrophilic polymeric blend (Eudragit RS and PEG6000) was used to control the release of RES. With the dispersive mixing and high shear forces of hot melt extrusion, the thermodynamic properties and dispersion of RES were changed to improve its solubility. The effects of the formulation were investigated through univariate analysis to optimize the preparation of the sustained-release solid dispersion. In vitro and in vivo studies were performed to evaluate the prepared RES/RS/PEG6000 sustained-release solid dispersion. The physical state of the solid dispersion was characterized using differential scanning calorimetry and X-ray diffraction. Surface properties of the dispersion were visualized using scanning electron microscopy, and the chemical interaction between RES and excipients was detected through Fourier-transform infrared spectroscopy. Results suggested that the optimized sustained-release solid dispersion was obtained when the mass ratio of RES-polymeric blend was 1:5, the ratio of PEG6000 was 35%, the barrel temperature was 170 °C, and the screw speed was 80 rpm. In vitro studies demonstrated that the solid dispersion showed a good sustained release effect. The cumulative release of RES reached 82.42% until 12 h and was fit by the Weibull model. In addition, the saturated solubility was 2.28 times higher than that of the bulk RES. In vitro studies demonstrated that the half-life increased from 3.78 to 7.09 h, and the bioavailability improved to 140.38%. The crystalline RES was transformed into the amorphous one, and RES was highly dispersed in the polymeric blend matrix.Keywords:solid dispersion;resveratrol;hot melt extrusion;dissolution;sustained-release

研究领域: 药剂学 · 生物制药
✓ 已验证 DOI PubMed 高影响因子
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NANOTECHNOLOGY · 2021 ·Vol. 33 ·期 3 ·035706 · IF 3.874

Functionalization of mesoporous silica as an effective composite carrier for essential oils with improved sustained release behavior and long-term antibacterial performance

Ximing Zhong,Fan Gao,Hongjie Wei,Hongjun Zhou,Xinhua Zhou

In this work, a novel composite carrier system for loading essential oils was developed by using tetraethyl orthosilicate (TEOS) and (3-aminopropyl) triethoxysilane (APTES) as silica precursors and cetyl trimethyl ammonium bromide (CTAB) as a template, and the resultant aminated mesoporous silica was further chemically modified by polyacrylic acid (PAA). The obtained composite carriers exhibited a high loading capability toward tea tree oil (TTO), and they also significantly improved the release behavior of TTO due to the steric hindrance of silica mesopore and the polymer restriction. Besides, it was found that the release behavior followed the First-Order kinetic model, revealing that the release of TTO was driven by the concentration gradient. In addition, these composite carriers with essential oil-loaded demonstrated remarkable antibacterial performance against E. coli and S. aureus, and they could retain antibacterial performance even after 50 d. Moreover, the antibacterial mechanism was also elucidated with the assistance of nucleic acid and conductivity measurements. Therefore, this work provides a facile and environmentally friendly approach to preparing effective composite carriers for improving the sustained release of essential oils, and the long-term antibacterial performance of these essential oil-loaded composite carriers makes them tremendously potential for practical applications.

研究领域: 材料科学 · 化学工程 · 药学 · 纳米技术
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ACS Applied Bio Materials · 2025 · IF 4.7

PLGA-Loaded Monascin Intranasal Delivery System: Sustained-Release and Immunomodulatory Effect for Treatment of Allergic Rhinitis by Improving Regulatory T Cell Function

Zhao Wang,Khawar Ali Shahzad,Ding Li,Boyu Cai,Zilin Huang,Maoxiang Xu,Jiaojiao Li,Dong Chen,Fei Tan

Monascin, a natural and safe drug, exhibits potent anti-inflammatory, hypolipidemic, and antioxidative effects. However, their therapeutic potential and underlying mechanisms in allergic rhinitis (AR) remain unexplored. The intranasal delivery of monascin for treating AR faces the challenge of rapid clearance. Herein, to achieve sustained and prolonged release, we developed monascin-encapsulated poly(lactic co glycolic acid) nanoparticles (PLGA-MS) by the mechanical double emulsion technique, enabling effective local delivery of monascin for the treatment of AR. Histopathological staining, flow cytometry, ELISA, and network pharmacology were used to assess therapeutic effects and potential mechanisms of monascin in treating AR. In vitro and in vivo experiments revealed that PLGA-MS exhibited enhanced stability, excellent drug encapsulation capacity, and sustained drug release. PLGA-MS treatment showed a significant therapeutic effect in AR mice by decreasing inflammatory cells in nasal tissue and regulating IgE, histamine, and a variety of cytokines. PLGA-MS treatment decreased T helper 2 cells (Th2) and T helper 17 cells (Th17) while promoting and increasing Tregs (regulatory T cells). Further analysis showed elevated levels of IL-10 and TGF-β expression in Tregs post-treatment. Results of the CCK-8 assay, pathological analysis of vital organs, and serum analysis of liver and kidney functions demonstrated the biosafety of PLGA-MS. Additionally, network pharmacology identified immune response pathways that may support PLGA-MS’s immunomodulatory effects in AR. Our study presented a biomaterial-facilitated intranasal delivery system for monascin, offering an effective therapeutic strategy for AR.

CAS / MDL: 9002-93-1
✓ 已验证 产品关联 DOI PubMed 高影响因子
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FOOD CHEMISTRY · 2026 · IF 10.4

Curcumin-loaded Pickering emulsion enhanced the sustained-release performance for chitosan coating and improved the postharvest quality of plum fruits (Prunus salicina)

Huanqi Wu,Yiqin Zhang,Yangyang Zhou,Xiangmeng Xiao,Yupei Gu,Wen Qin

CUR Pickering emulsion exhibited uniformity and stability. • CUR Pickering emulsion enhanced CS-based coating bioactivity and sustained release. • PE/CS coating maintained postharvest quality for plum fruits. Curcumin is a promising natural preservative, but its poor solubility and susceptibility to photo-oxidation limit its application in active coatings. This study developed a cellulose nanofiber-stabilized curcumin Pickering emulsion incorporated into chitosan for postharvest plum preservation. The Pickering emulsion prepared at a water-to-oil ratio of 40:10 ( w / w ) exhibited uniform droplet distribution and good electrostatic stability. Its incorporation enhanced the mechanical performance and water resistance of PE/CS coating films, while FTIR and XRD analyses indicated hydrogen-bonding interactions within the composite matrix. Notably, PE/CS coating films showed sustained curcumin release in 50% ethanol, reaching 65% after 96 h. This controlled-release behavior was associated with enhanced antimicrobial and antioxidant activities, as reflected by inhibition zones above 10 mm and DPPH/ABTS + scavenging rates exceeding 98%. PE/CS coating effectively delayed flesh browning, water loss, and firmness decline in plums, providing a Pickering emulsion-based strategy for active fruit preservation. Download: Download high-res image (177KB) Download: Download full-size image

✓ 已验证 DOI PubMed 高影响因子
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JOURNAL OF POWER SOURCES · 2022 · IF 9.794

Targeted stabilization of solid electrolyte interphase and cathode electrolyte interphase in high-voltage lithium-metal batteries by an asymmetric sustained-release strategy

Fengwei Bai,Yan Li,Ziyu Chen,Yongchao Zhou,Chengzong Li,Tao Li

High-voltage lithium (Li)-metal batteries with cell-level energy density over 350 Wh kg −1 are promising energy storage systems . However, the aggressive interphase chemistries associated with highly reactive Li-metal anode and high-voltage cathodes impede their practical applications. Herein, we demonstrate the targeted stabilization of solid electrolyte interphase (SEI) and cathode electrolyte interphase (CEI) in high-voltage Li-metal batteries by asymmetrically sustained-releasing different additives. An asymmetric sustained-release film loaded with lithium bis-(oxalate)borate (LiBOB) and LiNO 3 on each side is investigated as a proof-of-concept. The sustained-releasing of LiBOB and LiNO 3 can maintain a localized concentration at the high-voltage cathode and Li-metal anode fronts respectively, thus forming a stable B-containing CEI and N-containing SEI. As such, issues like dendrites growth, parasitic side reactions and transition metals dissolution under high-voltage are addressed simultaneously. Based on this strategy, the 30 μm Li|LiNi 0.5 Co 0.2 Mn 0.3 O 2 (4.1 mAh cm −2 ) batteries deliver a capacity retention of 80% after 173 cycles under a cut-off voltage of 4.5 V.

研究领域: 储能系统 · 电池技术 · 材料科学 · 电化学
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INTERNATIONAL JOURNAL OF PHARMACEUTICS · 2023 · IF 5.8

In situ formation of injectable organogels for punctal occlusion and sustained release of therapeutics: design, preparation, in vitro and in vivo evaluation

Ziqin Cao,Yangnan Chen,Shaoyun Bai,Zhiyun Zheng,Yan Liu,Shuangying Gui,Shuang Shan,Jiabao Wu,Ning He

The treatment of dry eye mainly includes instillation of cyclosporine A (CsA) nanoemulsion or the use of punctal plugs. Therefore, in this study, a novel injectable in situ organogel plug was developed using CsA as a model drug, stearic acid , injectable soybean oil, and N -methyl-2-pyrrolidinone (NMP) (1.25:10:0.6, w/v/v) as gel materials, to provide a dual mechanism for dry eye treatment. The formulated CsA injectable in situ organogel (CsA-OG) was evaluated in terms of stability, in vitro release, rheology, ocular irritation, punctal occlusion tests, and ocular distribution assessment. In vivo ocular distribution investigations showed that CsA-OG achieved considerably higher C max (1.94, 1.92 and 1.97-fold respectively) and AUC 0-72h in the cornea, conjunctiva, and sclera (2.49, 2.27 and 2.15-fold respectively) than ciclosporin eye drops ( p  < 0.05). In vitro model evaluation demonstrated significant decrease in flow flux to 52.78 % at 2 min after CsA-OG injection. According to evaluation of the in vivo model, the organogel plug can completely block the lacrimal passages and greatly decrease the lacrimal drainage rate ( p  < 0.05). The above results suggest that these intracanalicular CsA-OG plugs can offer more extensive clinical applications than existing lacrimal drainage plugs and may act as a drug delivery system .

✓ 已验证 产品关联 DOI PubMed 高影响因子
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ACS Nano · 2023 · IF 17.1

Cell-Free Osteoarthritis Treatment with Sustained-Release of Chondrocyte-Targeting Exosomes from Umbilical Cord-Derived Mesenchymal Stem Cells to Rejuvenate Aging Chondrocytes

Hongfu Cao,Manyu Chen,Xiaolin Cui,Yuan Liu,Yuhan Liu,Siyan Deng,Tun Yuan,Yujiang Fan,Qiguang Wang,Xingdong Zhang

As chondrocytes from osteoarthritic cartilage usually exhibit aging and senescent characteristics, targeting aging chondrocytes could be a potential therapeutic strategy. In this study, exosomes derived from umbilical cord-derived mesenchymal stem cells (UCMSC-EXOs) combined with the chondrocyte-targeting capacity and controlled-release system were proposed for osteoarthritis (OA) treatment via rejuvenating aging chondrocytes. The essential functional miRNAs within UCMSC-EXOs were investigated, with the p53 signaling pathway identified as the key factor. To improve the therapeutic efficiency and retention time of UCMSC-EXOs in vivo, the exosomes (EXOs) were engineered on membranes with a designed chondrocyte-targeting polymers, and encapsulated within thiolated hyaluronic acid microgels to form a “two-phase” releasing system, which synergistically facilitated the repair of OA cartilage in a rat model. Together, this study highlighted the rejuvenating effects of UCMSC-EXOs on OA chondrocytes and the potential to combine with chondrocyte-targeting and sustained-release strategies toward a future cell-free OA treatment.

CAS / MDL: 51805-45-9
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Bioengineering & Translational Medicine · 2022 ·Vol. 8 ·期 2 ·e10414 · IF 10.684

OP3-4 peptide sustained-release hydrogel inhibits osteoclast formation and promotes vascularization to promote bone regeneration in a rat femoral defect model

Peng Luo,Jiarui Fang,Dazhi Yang,Lan Yu,Houqing Chen,Changging Jiang,Rui Guo,Tao Zhu,Shuo Tang

Bone injury caused changes to surrounding tissues, leading to a large number of osteoclasts appeared to clear the damaged bone tissue before bone regeneration. However, overactive osteoclasts will inhibit bone formation. In this study, we prepared methacrylylated gelatin (GelMA)-based hydrogel to co-crosslink with OP3-4 peptide, a receptor activator of NF-κB ligand (RANKL) binding agent, to achieve the slow release of OP3-4 peptide to inhibit the activation of osteoclasts, thus preventing the long-term existence of osteoclasts from affecting bone regeneration, and promoting osteogenic differentiation. Moreover, CXCL9 secreted by osteoblasts will bind to endogenous VEGF and inhibit vascularization, finally hinder bone formation. Thus, anti-CXCL9 antibodies (A-CXCL9) were also loaded in the hydrogel to neutralize excess CXCL9. The hydrogel slow released of OP3-4 cyclic peptide and A-CXCL9 to simultaneously inhibiting osteoclast activation and promoting vascularization, thereby accelerating the healing of femur defect. Further analysis of osteogenic protein expression and signal pathways showed that the hydrogel may be through activating the AKT-RUNX2-ALP pathway and ultimately promote osteogenic differentiation. This dual-acting hydrogel can effectively prevent nonunion caused by low vascularization and provide long-term support for the treatment of bone injury.

CAS / MDL: 2386-53-0 301-10-0
✓ 已验证 产品关联 DOI PubMed 高影响因子
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INORGANIC CHEMISTRY · 2021 · IF 5.165

Loading and Sustained Release of Pralidoxime Chloride from Swellable MIL-88B(Fe) and Its Therapeutic Performance on Mice Poisoned by Neurotoxic Agents

Dianfa Zhao,Jie Liu,Lijuan Zhang,Yunshan Zhou,Yuxu Zhong,Yang Yang,Chengcheng Huang,Yong’an Wang

Maintaining a long-term continuous and stable reactivator blood concentration to treat organophosphorus nerve agent poisoning using acetylcholinesterase (AChE) reactivator pralidoxime chloride (2-PAM) is very important yet difficult. Because the flexible framework of MIL-88B(Fe) nanoparticles (NPs) can swell in polar solvents, pralidoxime chloride (2-PAM) was loaded in MIL-88B(Fe) NPs (size: ca. 500 nm) by stirring and incubation in deionized water to obtain 2-PAM@MIL-88B(Fe), which had a maximum drug loading capacity of 12.6 wt %. The as-prepared composite was characterized by IR, powder X-ray diffraction (P-XRD), scanning electron microscopy (SEM), ζ-potential, Brunauer–Emmett–Teller (BET), and thermogravimetry/differential thermal analysis (TG/DTA). The results showed that under constant conditions, the maximum drug release rates of 2-PAM@MIL-88B(Fe) in absolute ethanol, phosphate-buffered saline (PBS) solution (pH = 7.4), and PBS solution (pH = 4) at 150 h were 51.7, 80.6, and 67.1%, respectively. This was because the composite showed different swelling behaviors in different solvents. In PBS solution with pH = 2, the 2-PAM@MIL-88B(Fe) framework collapsed after 53 h and released 100% of 2-PAM. For mice after intragastric poisoning with sarin (a neurotoxic agent), an atropine-assisted 2-PAM@MIL-88B(Fe) treatment experiment revealed that 2-PAM@MIL-88B(Fe) continuously released 2-PAM for more than 72 h so that poisoned AChE was continuously and steadily reactivated. The reactivation rate of AChE was 56.7% after 72 h. This composite is expected to provide a prolonged, stable therapeutic drug for the mid- and late-stage treatment of neurotoxic agent poisoning.

✓ 已验证 产品关联 DOI PubMed 高影响因子
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FOOD RESEARCH INTERNATIONAL · 2015 · IF 2.818

Gel-like pea protein Pickering emulsions at pH 3.0 as a potential intestine-targeted and sustained-release delivery system for β-carotene

Yun Shao,Chuan-He Tang

In recent years, there is increasing interest in the development of food-grade Pickering emulsions as promising delivery systems for bioactive compounds . Our previous work reported that most of the proteins in pea protein isolate (PPI) at pH   3.0, present in the nanoparticle form, can effectively perform as a kind of food-grade Pickering stabilizers for oil-in-water emulsions (LWT, 2014). The purpose of this study was to further report that PPI-stabilized emulsions at pH   3.0 exhibited great potential to act as intestine-targeted and sustained-release delivery systems for β -carotene. The emulsions were produced by microfluidization at a specific protein concentration of 6.0% (w/v) and varying oil fractions ( ϕ ) of 0.2–0.6. The results indicated that increasing ϕ was favorable for the gel-like network strengthening of these emulsions. The gel formation was largely related to the droplet flocculation as well as inter-floc attractive interactions. The in vitro simulated digestion results showed that the release of β -carotene during the intestinal digestion of these emulsions could be well modulated by altering ϕ . The gel-like emulsion at ϕ   =   0.6 exhibited much lower release of β -carotene, but higher stability towards degradation during the digestion, than that at ϕ   =   0.3. The findings provide important information not only for the design of novel delivery systems for lipophilic bioactive components, but also for the development of plant protein-based formulations.

CAS / MDL: 7235-40-7
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JOURNAL OF HAZARDOUS MATERIALS · 2024 · IF 12.2

Effects of artemisinin sustained-release algaecides on in-situ cyanobacterial inhibition and microbes-floating plants dominated ecosystem functions in artificial landscape lake

Yushen Ma,Xiaoming Zhu,Lixiao Ni,Cunhao Du,Wenlu Sang,Chu Xu,Jiahui Shi,Yiping Li,Shiyin Li,Yalun Pang,Linyun Zhang

The artemisinin sustained-release algaecides (ASAs) have been proven to be a safe and effective mean of inhibiting cyanobacteria in laboratory experiments. However, their effectiveness and impacts on ecosystem functions (EF) in natural waters are still unclear. In this study, the in-situ inhibitory effect of ASAs on cyanobacteria in natural waters was investigated over a period of 110 days to assess EF impacts dominated by microbes and floating plants. The results indicated that ASAs had a long-term inhibitory effect on cyanobacteria. ASAs did not affect sediment but increased TOC and TP in the water column in 2–10 days. Microbial diversity and network analyses indicated that ASAs enhanced bacterial diversity, network complexity, and hub-bacteria in networks. Metabolic pathway predictions and CCA analysis showed that ASAs maintained the stability of EF by enhancing the metabolic capacities of bacteria, and the relationships between metabolic microorganisms and environmental factors. PLS-PM revealed that ASAs primarily drove bacterial resistance to cyanobacteria, which was the key mechanism for its long-term inhibition of cyanobacteria. However, the early outbreak of floating plants was not conducive to the long-term inhibition of cyanobacteria by ASAs. This study provides new insights into the mechanisms and ecological impacts of cyanobacterial inhibition by ASAs in complex aquatic environments.

CAS / MDL: 9012-76-4
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JOURNAL OF FOOD SCIENCE · 2024 ·Vol. 89 ·期 5 ·2879-2894 · IF 3.2

Mechanical properties, sustained release, and oxygen scavenging properties of nanocomposite films loaded with bimetallic nanoparticles (Fe2O3/TiO2) in extra virgin olive oil

Mahsa Kheirandish,Majid Javanmard dakheli,Maryam Mizani,Alireza Salehirad

The aim of this study was the synthesis of bimetallic nanoparticles based on Fe 2 O 3 /TiO 2 and its use in the poly(lactic acid) (PLA) films as an oxygen scavenger in extra virgin olive oil (EVOO) packaging. Bimetallic nanocomposites were prepared by two different precipitation methods (precipitation with ammonia and sodium hydroxide). The characteristics of bimetallic nanoparticles precipitated with sodium hydroxide (Na-Ti 0.01 Fe 0.048 O 0.08 ) and bimetallic nanoparticles precipitated with ammonia (NH-Ti 0.01 Fe 0.022 O 0.09 ) were compared. Relative amounts of elements in bimetallic nanocomposites and their morphological characteristics were determined using field emission scanning electron microscopy coupled with energy-dispersive X-ray spectrometer. Porosity volume and surface area of bimetallic nanoparticles were calculated using adsorption–desorption isotherms and the Brunauer–Emmett–Teller method. The formation/characterization of bimetallic nanoparticles and their location in the matrix of PLA-based nanocomposite film was studied using X-ray diffraction and Fourier transform infrared. In nanocomposite films based on PLA, bimetallic nanoparticles lead to better oxidative stability (peroxide value, p -anisidine index, K 232 , and K 270 ) of the EVOO and oxygen scavenging during storage compared to free nanoparticles. Mechanical properties of nanocomposite films were improved due to bimetallic nanoparticles, which were better for Na-Ti 0.01 Fe 0.048 O 0.08 . In vitro release modeling of the bimetallic nanoparticles in EVOO proved that Fickian diffusion is the dominant mechanism, and the Peleg model was the best description of the release behavior of nanoparticles.

CAS / MDL: 10025-77-1
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