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Biomaterials Research · 2024 · IF 8.1

An In Situ Sustained-Release Chitosan Hydrogel to Attenuate Renal Fibrosis by Retaining Klotho Expression

Chenyang Li,Shuai Wang,Chenghui Liao,Ying Li,Yunfeng Zhou,Haiqiang Wu,Wei Xiong

Klotho (KLO) is an anti-fibrotic protein expressed in the kidneys and has been decreasing in the development of renal fibrosis (RF). However, restoring the decline in KLO levels remains a great challenge during RF treatment. Herein, an injectable KLO-loaded chitosan (CS) hydrogel (KLO-Gel) is designed to achieve localized and prolonged release of KLO in the RF treatment. KLO-Gel was prepared by cross-linking CS with β-glycerophosphate (β-GP), followed by rapid (within 3 min) thermosensitive gelation at 37 °C. Furthermore, KLO-Gel exhibited a slow and sustained release (over 14 d) of KLO both in PBS and in the kidneys of mice with unilateral ureter obstruction (UUO). A single local injection of KLO-Gel into the renal capsule of UUO mice was more effective at reducing RF (i.e., maintaining renal function and tissue structure, alleviating extracellular matrix accumulation, and inhibiting the TGF-β1/Smad2/3 signaling pathway) over a 14-d period than daily intraperitoneal injections of free KLO or captopril. Crucially, CS was found to induce endogenous KLO secretion, highlighting the added value of using CS in RF treatment. Overall, this study demonstrated that KLO-Gel enhanced the anti-fibrotic efficacy of KLO while minimizing its off-target toxicity, and its clinical potential awaits further validation.

CAS / MDL: 154804-51-0
研究领域: 药理学 · 生物医学工程 · 肾脏病学
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FOOD CHEMISTRY · 2025 · IF 9.8

Sustained release of gaseous chlorine dioxide from alpha-cyclodextrin: An innovative method for strawberry preservation

Linyan Chen,Haohan Jing,Yuhe Dong,Yuantong Cao,Tong Wu,Wanying Zhu,Fanwei Dai,Minhui Chen,Yao Liu,Nan He,Ran Huang,Tian Zhong

The traditional method of generating chlorine dioxide (ClO 2 ) involves reacting sodium chlorite with acid on-site, posing high safety risks of concentrated ClO 2 . This study encapsulates ClO 2 molecules directly in α-cyclodextrin (α-CD) to form inclusion complexes (ClO 2 @α-CD). This approach enables stable storage and safe handling of gaseous ClO 2 , while its sustained-release property also provides long-term microbial inhibition. Fumigation with 0.25 g of ClO 2 @α-CD completely inhibited Aspergillus niger growth on potato dextrose agar (PDA). A 0.5 g dose reduced the 6-day decay incidence of A. niger -inoculated strawberries from 91.67 % (control) to 5.00 % and the severity from 58.75 % (control) to 1.25 %. In commercial storage simulations, 5 g of ClO 2 @α-CD reduced the natural incidence from 53.33 % (control) to 26.67 %, while preserving the weight, color, firmness, and total soluble solids (TSS)/titratable acidity (TA) ratio of strawberries. These findings suggest that ClO 2 @α-CD is a viable approach for controlling postharvest diseases and prolonging fruit shelf-life.

CAS / MDL: 10016-20-3
研究领域: 食品科学 · 植物病理学 · 化学工程
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Expert Opinion on Drug Delivery · 2024 · IF 5

Sustained release of brimonidine from conjunctival sac insert to reduce intraocular pressure for glaucoma treatment

Zhutian Zhang,Qian Ma,Zhaoxing Dai,Jiaxu Hong,Jifeng Gu,Rong Shi,Jianjiang Xu,Yaling Ma,Xinghuai Sun,Jianguo Sun

Background Glaucoma is one of the major irreversible blinding eye diseases in the world. Reducing intraocular pressure (IOP) is the primary treatment option, and taking eye drops daily is the common method. However, short drug duration and poor bioavailability of eye drops may lead to unsatisfied therapeutic effects and inadequate patient compliance.Methods A brimonidine-loaded silicone rubber insert (BRI@SR@PT) was prepared by loading brimonidine into a surface-modified silicone rubber ring, followed by polydopamine/thermoplastic polyurethane coatings. The physical properties, in vitro cytocompatibility and drug release of BRI@SR@PT were investigated. The BRI@SR@PT was administrated in the conjunctival sac of rabbit eyes, and its in vivo drug release, IOP-lowering efficacy and biosafety were assessed.Results The BRI@SR@PT presented great thermal stability and excellent elasticity. The BRI@SR@PT was able to release BRI sustainably for 28 days with little toxicity in vitro. Compared to BRI eye drops, the BRI@SR@PT effectively lowered IOP for 21 days based on the sustained BRI release with great biosafety when administrated in conjunctival sac of rabbit eyes in a noninvasive fashion.Conclusions The conjunctival sac insert (BRI@SR@PT), as a promising drug-delivery platform, may provide a sustained IOP-lowering treatment for patients with ocular hypertension or glaucoma, without the need for invasive procedures.

研究领域: 药剂学 · 眼科医学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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COLLOIDS AND SURFACES B-BIOINTERFACES · 2022 · IF 5.999

One-step emulsification for controllable preparation of ethyl cellulose microcapsules and their sustained release performance

Xu-Chun Song,Ya-Lan Yu,Gui-Yuan Yang,A.-Li Jiang,Ying-jie Ruan,Shang-hua Fan

A simple and versatile strategy for controlled production of monodisperse ethyl cellulose (EC) microcapsules by a single-stage emulsification method has been developed. Monodisperse oil-in-water emulsions, obtained by a microfluidic device, are used as templates for preparing EC microcapsules. Oil-soluble ethyl acetate (EA) is miscible with water, so the interfacial mass transfer between EA and water occurs sufficiently, which leads to water molecules pass through the phase interface and diffuse into emulsion interior. Water molecules aggregate at the interface, and some merge into a large water drop in the central position of the emulsion. After evaporation of EA solvent, monodisperse EC microcapsules create large numbers of pits on the surface with a hollow structure. Curcumin is used as a model drug and embedded in the hollow structure. EC microcapsules have good, sustained drug release efficacy in a simulated intestinal environment, and the release process of EC microcapsules containing 6.14% drug-loaded capacity is fully consistent with the vitro drug release model. Such simple techniques for making EC microcapsules may open a window to the controlled preparation of other multifunctional microcapsules. Besides, it offers theoretical guidance for the study of EC microcapsules as drug carriers and expanding clinical application of curcumin.

研究领域: 药剂学 · 材料科学
✓ 已验证 DOI PubMed 高影响因子
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INTERNATIONAL JOURNAL OF PHARMACEUTICS · 2019 · IF 4.213

Highly bioactive, bevacizumab-loaded, sustained-release PLGA/PCADK microspheres for intravitreal therapy in ocular diseases

Jiaxin Liu,Shuang Li,Ge Li,Xiang Li,Changhui Yu,Zhijiang Fu,Xiangyu Li,Lesheng Teng,Youxin Li,Fengying Sun

Bevacizumab, a vascular endothelial growth factor (VEGF)-targeting drug, is widely used as an off-label therapeutic for age-related macular degeneration (AMD). To reduce the monthly administration frequency, this study investigated microspheres comprising a poly( d , l -lactide-co-glycolide)/poly(cyclohexane-1,4-diyl acetone dimethylene ketal) (PLGA/PCADK) blend that could be loaded with bevacizumab-dextran particles using solid-in-oil-in-water (S/O/W) emulsification. Control microspheres were also prepared through water-in-oil-in-water (W/O/W) emulsification. The structural stability of bevacizumab in the polymer monomers was analyzed using dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), size exclusion chromatography (SEC-HPLC), circular dichroism (CD) and fluorescence spectroscopy. Subsequently, microspheres were prepared and evaluated in terms of their morphology, encapsulation efficiency and release behavior. PLGA/PCADK microspheres prepared by the S/O/W method with <20% PCADK showed a smooth spherical structure with a uniform distribution of bevacizumab. The microspheres exhibited a release behavior comprising a slight initial burst and an increasing total release over 50 days both in vitro and in vivo . Additionally, the microspheres were well tolerated by ocular tissue. Finally, a chorioallantoic membrane (CAM) assay revealed that the bioactivity of bevacizumab was retained by PCADK. In conclusion, these results suggest the potential for bevacizumab-loaded PLGA/PCADK microspheres prepared by the S/O/W method as a means of intravitreal therapy for ocular diseases.

研究领域: 药物学 · 眼科学 · 药物递送系统
✓ 已验证 DOI PubMed 高影响因子
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JOURNAL OF PHYSICS D-APPLIED PHYSICS · 2020 ·Vol. 53 ·期 24 ·245401 · IF 3.169

Magnetic drug-loaded osteoinductive Fe3O4/CaCO3 hybrid microspheres system: efficient for sustained release of antibiotics

Jingyi Xue,Xiaolei Li,Qianli Li,Jiahong Lyu,Wei Wang,Lin Zhuang,Yue Xu

A novel magnetic drug-loaded osteoinductive Fe3O4/CaCO3 hybrid microspheres system (MDHMs) with excellent drug delivery property has been fabricated by a modified coprecipitation method. The MDHMs are uniform vaterite microspheres with well-defined mesoporous nanostructures. The formation of vaterite is based on the templating effect of casein micelles, which is promising in bone tissue engineering. Cyclodextrins (CDs) increase the porosity of the microspheres with a pore size of about 7.3 nm and a surface area of about 50.73 m2 g−1. The mesoporous structure gives the MDHMs great drug loading efficiency of about 80.75–88.74% and the minocycline-loaded MDHMs display a sustained drug release property (about 95% in 5 d). Moreover, the MDHMs also possess stable magnetic property with a saturation magnetization of about 4.41 emu g−1 and a remarkable magnetism-responsive behavior. These results demonstrate that with superior drug delivery property, osteoinductive potential and magnetic property, the MDHMs have a great potential in the treatment of peri-implantitis.

研究领域: 材料科学 · 药剂学 · 生物医学工程
✓ 已验证 DOI 高影响因子
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CELLULOSE · 2021 ·Vol. 28 ·期 3 ·1587-1597 · IF 5.044

An injectable thermo-responsive hydrogel based cellulose-brush derivative for the sustained release of doxorubicin

Liu Xiaohong,Li Ming,Zhang Haichuan,Chen Liheng,Fu Shiyu

A cellulose- grafted -poly( N -isopropylacrylamide) (cellulose- g -PNIPAAm) copolymer with thermo-responsivity was synthesized using homogeneous activators regenerated by electron transfer for atom transfer radical polymerization (ARGET-ATRP). The prepared copolymer dispersed at low concentration in water or phosphate-buffered saline (PBS) at 25 °C could self-assembly into micelles at 37 °C. The size and morphology of these micelles were determined by dynamic light scattering and transmission electron microscopy. The copolymer at a concentration over 4.2% by weight in water formed an injectable thermo-responsive hydrogel that was composed of micelles when the temperature increased to 37 °C. This hydrogel was used to load the anticancer drug doxorubicin (DOX). In vitro release studies demonstrated that this hydrogel released DOX in a sustained manner. Furthermore, this cellulose-based injectable thermo-responsive hydrogel was used in cytotoxicity tests, revealing that it was very biocompatible. Based on the above results, this cellulose- g -PNIPAAm injectable thermo-responsive hydrogel has strong potential for application in smart drug delivery systems.

研究领域: 材料科学 · 生物医药 · 高分子化学
✓ 已验证 DOI 高影响因子
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ACS Applied Materials & Interfaces · 2021 · IF 9.229

Water- and Acid-Sensitive Cu2O@Cu-MOF Nano Sustained-Release Capsules with Superior Antifouling Behaviors

Huali Li,Shuwen Luo,Liuqin Zhang,Zilong Zhao,Min Wu,Weihua Li,Fa-Qian Liu

Marine biofouling is one of the technical bottlenecks restricting the development of the global marine economy. Among the commercial self-polishing antifouling coatings, cuprous oxide is an irreplaceable component because of its efficiency and broad-spectrum antibacterial activity. However, one of the biggest obstacles to achieving long-term antifouling is the “initial burst and final decay” of cuprous oxide in the coating. Here, we lock the copper ions by establishing an antifouling unit composed of Cu2O (core) and Cu-based metal–organic framework (Cu-MOF, shell). Cu-MOF is densely grown in situ on the periphery of Cu2O by acid proton etching. The shell structure of Cu-MOF can effectively improve the stability of the internal Cu2O and thus achieve the stable and slow release of copper ions. Furthermore, Cu2O@Cu-MOF nanocapsules can also achieve active defense by rapid and complete dissolution of Cu2O@Cu-MOF at local acidic microenvironment (pH ≤ 5) where the adhesion of fouling organisms occurs. Super-resolution fluorescence microscopy is used to explain the sterilization mechanism. Relying on the water- and acid-sensitive properties of Cu-MOF shell, the stable, controlled and efficient release of copper ions has been achieved for the Cu2O@Cu-MOF nanocapsules in the self-polishing antifouling coatings. Thus, these controlled-release nanocapsules make long-term antifouling promising.

研究领域: 材料科学 · 海洋生物学 · 化学工程
✓ 已验证 DOI PubMed 高影响因子
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Journal of Orthopaedic Surgery and Research · 2021 ·Vol. 16 ·期 1 ·1-9 · IF 2.359

Intra-articular injection of loaded sPL sustained-release microspheres inhibits osteoarthritis and promotes cartilaginous repairs

Li Jiyou,Liu Ning,Huang Zhipeng,Wang Wantao,Hou Donghua,Wang Wenbo

Background Osteoarthritis is a chronic inflammatory disease of the joints associated with significant morbidity and lower quality of life. Current treatment strategies focus on reducing cartilage degeneration but fail to restore their proliferative ability. Super-activated platelet lysate (sPL) is an enhanced form of platelet-rich plasma that can be easily inactivated. The purpose of this study is to evaluate whether sPL-loaded PLGA/chitosan/gelatin microspheres can prevent and treat osteoarthritis. Methods Features of biological microspheres were detected by SEM and ELISA. Osteoarthritis chondrocytes were co-cultured with hydrogel loaded with sPL. The effect of biological microspheres on chondrocyte proliferation was evaluated using a CCK-8 cell proliferation test. Cell morphology and cell necrosis were measured with a microscope. The gene expression levels of cartilage-related markers type 2 collagen, aggrecan (ACAN), and SRY type high mobility group box-9 (SOX9) were determined by real-time quantitative polymerase chain reaction (Rt-PCR). A rat osteoarthritis model was established. Micro-CT was used to characterize cartilaginous changes after the injection of biological microspheres. Histopathological HE staining, Safranin-O Fast Green staining and staining scores, type II collagen staining, and proteoglycan staining were used to evaluate the degree of cartilaginous repair. Results Biological microspheres were able to continuously release biological factors. Exposure to loading sPL microspheres significantly increased chondrocyte proliferation, reduced cell necrosis, and increased the expression of cartilage markers type 2 collagen, ACAN, and SOX9 in osteoarthritic chondrocytes. In vivo experiments found that biological microspheres also smoothen cartilage surfaces, promote the expression of proteoglycan and type 2 collagen while also increasing cartilaginous integrity as evaluated using Safranin-O Fast Green staining. Conclusions PLGA/chitosan/gelatin hydrogel loaded with sPL is a promising tool for effective and non-invasive articular cartilage repair in osteoarthritis. Graphic abstract Biological microspheres loaded with sPL release various biological factors to promote chondrocyte proliferation and upregulate chondrocyte functionalization genes (SOX9, CoX II, ACAN), leading to an overall enhanced cartilaginous matrix.

研究领域: 骨科 · 生物医学工程 · 药理学
✓ 已验证 DOI PubMed 高影响因子
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COLLOIDS AND SURFACES B-BIOINTERFACES · 2024 · IF 5.4

Preparation and sustained-release mechanism of hydroxybutyl chitosan/graphene oxide temperature-sensitive hypoglycaemic subcutaneous implants

Li Li,Fengting Xiang,Fan Wang,Anqi Chen,Yu Liu

The current situation of diabetes prevention and control is extremely severe. For instance, glimepiride (GLM), a third-generation sulfonylurea, demonstrates suboptimal clinical efficacy in oral dosage forms, which underscores the pressing need for the development of a new dosage form. Recently, in situ gel subcutaneous implants have garnered considerable attention. Hydroxybutyl chitosan (HBC) can spontaneously crosslink to form a thermosensitive hydrogel and has good biocompatibility. However, its application is hindered by its limited mechanical properties. Graphene oxide (GO), known for its stable dispersion in water, can load GLM through π–π stacking interactions. When combined with HBC, GO enhances the mechanical properties and stability of the hydrogel. Therefore, an HBC–GO@GLM hydrogel was prepared. Rheological analysis revealed that the incorporation of GO increased the critical gelation temperature of the 5 wt% HBC hydrogel from 19.1°C to 27.2°C, considerably enhancing the mechanical properties of the hydrogel. Using encapsulation efficiency as an evaluation index, the optimal encapsulation efficiency of GO@GLM was determined to be 73.53% ± 0.45% with a drug loading capacity of 27.39 ± 0.17% using the Box–Behnken design model. Computer simulation technology validated the interaction between the materials and the drug release mechanism. Pharmacokinetic results showed that compared to the HBC@GLM group, the half-life (t1/2), mean residence time and the area under the curve for the HBC–GO@GLM group were approximately 3 times those of the HBC@GLM group. Subcutaneous implantation of the HBC–GO@GLM hydrogel for drug delivery considerably extended the drug’s action time in the body, thereby maintaining blood sugar levels within a normal and stable range for an extended period.

CAS / MDL: 106-88-7
研究领域: 药剂学 · 生物医学工程 · 糖尿病治疗
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ACS Sustainable Chemistry & Engineering · 2024 · IF 7.1

Preparation and Application of Sustained-Release Antibacterial Alginate Hydrogels by Loading Plant-Mediated Silver Nanoparticles

Qingyin Dai,Ruijing Jia,Han Li,Jisheng Yang,Zhiyong Qin

Silver nanoparticles (AgNPs) are broad-spectrum antibacterial agents that are safe for the environment and the human body. To achieve a balance between material functionality, degradability, and safety of AgNPs, the peanut red skin (PSE)/polyphenol-hydroxypropyl-β-cyclodextrin (HPβCD)/AgNPs were prepared for the first time by ultrasound-triggered molecular encapsulation and biosynthesis for hydrophilic fusion of medicine and small molecules. Additionally, a novel “controlled release” sodium alginate (SA)-based hydrogel was developed and medicine/small-molecule self-assembled PSE/HPβCD/AgNPs were introduced into the three-dimensional network structure of the SA hydrogels. The SA-based hydrogels exhibited excellent mechanical and rheological properties. In different pH conditions, the hydrogels exhibit differing release and expansion behaviors, and the maximum cumulative release of AgNPs was 98.21% at pH > 6.8. Furthermore, the hydrogels exhibited strong antibacterial effects against pathogenic bacteria. They also showed excellent antioxidant properties and cytocompatibility. These advantages highlight the potential utility of the developed hydrogels for biomedical applications and agricultural fields.

CAS / MDL: 16940-66-2
研究领域: 材料科学 · 生物医学工程 · 纳米生物学
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LANGMUIR · 2024 · IF 3.7

Gelation Behavior and Drug Sustained-Release Properties of a Helix Peptide Organohydrogel with pH Responsiveness

Jiahui Zhang,Dongxin Zhao,Kui Lu,Libo Yuan,Heng Du

Based on the typical similar repeat units (abcdefg)n of α-helical structure, the peptide H was designed to self-assemble into an organohydrogel in response to pH. Depending on the different pH, the proportions of secondary structure, microstructure, and mechanical properties of the gel were investigated. Circular dichroism (CD) and Fourier transform infrared (FT-IR) showed that the proportion of α-helical structure gradually increased to become dominant with the increase of pH. Combining transmission electron microscopy (TEM) and atomic force microscopy (AFM), it was found that the increase of the ordered α-helix structure promoted fiber formation. The further increase in pH changed the intermolecular forces, resulting in an increase in the α-helix content and the enhancement of helix–helix interaction, causing the gel fibers to converge into thicker and more dense ones. The temperature test showed the stable rheological properties of the organohydrogel between 20–60 °C. Drug release and cytotoxicity showed that the DOX-loaded organohydrogel could have a better release in an acidic environment, indicating its potential application as a drug local delivery carrier.

研究领域: 生物化学 · 材料科学 · 药学
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