查找使用阿拉丁产品的科研文献

Synthesis and crystallization of well-defined biodegradable miktoarm star PEG-PCL-PLLA copolymer

Xinyu Peng,Yixin Zhang,Ying Chen,Sai Li,Bin He

A well-defined miktoarm star copolymer (μ-PEG-PCL-PLLA) was synthesized and the crystallization behavior of the copolymers was investigated. The structure of copolymer was confirmed by 1 H NMR, the molecular weight and molecular weight distribution were studied by GPC . XRD and POM were used to study the crystallization behavior of the miktoarm star copolymers. The XRD spectra showed that the miktoarm star copolymer showed low crystallinity for the joint of terminal, which limited the mobility of polymeric chains. The POM photographs revealed that PCL segments formed spherulites with PLLA crystalline grains as nucleus due to the good compatibility between PCL and PLLA.

Improved surface adhesion and wound healing effect of madecassoside liposomes modified by temperature-responsive PEG-PCL-PEG copolymers

Meifeng Liu,Weichi Chen,Xingyu Zhang,Pengwen Su,Feng Yue,Shaoqun Zeng,Song Du

Madecassoside (MA) exhibits excellent therapeutic effects in wound healing and scar management. However, its high hydrophilic nature and low permeability through skin tissue limits its topical application. Liposomes are widely used to deliver drugs due to their high structural similarity and biocompatibility with cell membranes. However, normal liposome formulations are too fluid to maintain sufficient adhesion to the wound surface. In this study, in order to make an MA formulation conducive to topical administration, poly(ethylene glycol)-poly( ε -caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG, PECE), a biodegradable and temperature-responsive copolymer material, was synthesized and applied to improve the adhesion properties of MA liposomes. The mean particle size of the PECE-modified MA liposomes was 213.43±4.68 nm, and the zeta potential was −23.80±15.37 mV under the optimal conditions of EPC (egg yolk lecithin) to PECE at a mass ratio of 1:1. Additionally, PECE-modified MA liposomes maintained a hydrogel state for better adhesion until the temperature reached 43°C. Furthermore, the PECE-modified MA liposomes showed superior wound contraction effects relative to the MA liposomes in second-degree burn experiments using a rat model. These results indicated that PECE-modified MA liposomes have better surface adhesion performance and healing effects than unmodified MA liposomes.

Crystallization enhanced thermal-sensitive hydrogels of PCL-PEG-PCL triblock copolymer for 3D printing

Yuecheng Cui,Ronghua Jin,Yang Zhou,Meirong Yu,Yun Ling,Li-Qun Wang

Temperature-sensitive hydrogels with mild gel-forming process, good biocompatibility and biodegradability have been widely studied as bioinks and biomaterial inks for 3D bioprinting. However, the hydrogels synthesized via copolymerization of aliphatic polyesters and polyethylene glycols have low mechanical strength and cannot meet the needs of 3D printing. In this paper, we propose a strategy of enhancing the strength of hydrogels by introducing crystallization between blocks to meet the requirements of 3D bioprinting inks. A series of polycaprolactone-polyethylene glycol-polycaprolactone (PCL-PEG-PCL) triblock polymers were prepared by ring-opening polymerization, of which the strong crystallinity of polycaprolactone blocks improved the printability and enhanced the mechanical properties of the ink. It was found that the resulted hydrogels were temperature-responsive, and the PCL blocks could form a crystalline phase in the state of the hydrogel, thereby significantly increasing the modulus of the hydrogel. Moreover, the mechanical strength of the hydrogel could be adjusted by changing the composition ratio of each block of the copolymer. The 3D printing results showed that the PCL-PEG-PCL hydrogel with crystallinity can not only be extruded and printed via temperature adjustment, but also the three-dimensional structure can be effectively maintained after 3D printing. The gels demonstrated good cell compatibility, and the cell survival rate was maintained at a high level.

Targeted delivery of ginsenoside compound K using TPGS/PEG-PCL mixed micelles for effective treatment of lung cancer

Lei Yang,Zhenghai Zhang,Jian Hou,Xin Jin,Zhongcheng Ke,Dan Liu,Mei Du,Xiaobing Jia,Huixia Lv

Ginsenoside compound K (CK) is one of the effective ingredients in antitumor composition of ginsenoside. However, the poor water solubility and significant efflux have limited the widespread clinical use of CK. In this study, preparation of novel CK-loaded d -alpha-tocopheryl polyethylene glycol 1,000 succinate/poly(ethylene glycol)-poly(ε-caprolactone) mixed micelles (CK-M) is discussed to solve the above problems. Particle size, zeta potential, and morphology were characterized using dynamic light scattering and transmission electron microscopy. CK-M are spherical shaped with an average particle size of 53.07±1.31 nm with high drug loading of 11.19%±0.87% and entrapment efficiency of 94.60%±1.45%. Water solubility of CK was improved to 3.78±0.09 mg/mL, which was ~107.35 times higher than free CK. A549 and PC-9 cells were used to evaluate in vitro cytotoxicity and cellular uptake. IC 50 values of CK-M in A549 and PC-9 cells (24 h) were 25.43±2.18 and 18.35±1.90 μg/mL, respectively. Enhanced cellular uptake of CK-M was observed in both cells. Moreover, CK-M promoted tumor cell apoptosis, inhibited tumor cell invasion, metastasis, and efflux through regulation of Bax, Bcl-2, matrix metalloproteinase-2, Caspase-3, and P-glycoprotein. In vivo imaging indicated that CK-M has excellent tumor targeting effect within 24 h, and the relative tumor inhibition rate of CK-M was 52.04%±4.62% compared with control group ( P <0.01). Thus, CK-M could be an appropriate delivery agent for enhanced solubility and antitumor effect of CK.

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

Oral delivery of WR-1065 by ROS-responsive PEG-PCL nanoparticles for radioprotection

Xiaona Lin,Xinxin Wang,Hongqi Tian

When a burst of reactive oxygen species (ROS) is induced after radiation exposure, a sufficient radioprotector drug must be quickly released to neutralize the ROS . An oral polymeric carrier of poly(ε-caprolactone)-b-poly(ethylene glycol)-b-poly(ε-caprolactone) was synthesized via the ROS-response linker thioketal (TK-linked PCEC) and used for delivery of the drug WR-1065. The drug-loaded nanoparticles (PCEC/WR-1065 NPs) had high WR-1065 content (19.7 % w/w) in the core and a particle size of 183 nm. The PCEC/WR-1065 NPs could protect the drug from degradation at gastric pH. More than 70 % of the TK-linked PCEC copolymer could be cleaved in 1 h. Therefore, a sufficient amount of WR-1065 could be quickly released from the PCEC/WR-1065 NPs to neutralize the burst of free radicals generated under irradiation. The in vitro cell uptake results of TK-linked PCEC NPs indicated that the NPs could be efficiently endocytosized by Caco-2 cells. Oral administration of the PCEC/WR-1065 led to survival benefit as well as protective effects on hematopoiesis and main organs with respect to the irradiation and oral free WR-1065 groups after 7.2 and 8.0 Gy total body irradiation, respectively. In vivo biodistribution studies indicated that the PCEC/WR-1065 NPs accumulated mainly in intestinal tissue. These results suggest that the design presented here provides a promising oral ROS-sensitive platform for acute radiation syndrome.

Metabolomic and Proteomic Analyses Unveil That Polyethylene Glycol–Polycaprolactone-Loaded Curcumin Nanoparticles Induce Mitochondrial Dysfunction and Metabolic Reprogramming to Suppress Melanoma Growth

Yixun Zhang,Xin Zhou,Wenlian Zheng,Jianwei Chen,Qianfeng Xu,Zhenguo Liang,Hongli Zhang,Jundong Lin,Wenjie Xie,Yangjia Zhuo,Muqi Chen,Fen Zou,Biyan Wen,Zeheng Tan,Weide Zhong,Huikang Yang,Ronghua Yang

Melanoma is highly dependent on cellular metabolism, but current treatments show limited effectiveness. Despite the promising antitumor properties of curcumin, its clinical utility is limited by its poor bioavailability and potential systemic toxicity. To address these challenges, we formulated curcumin-loaded polyethylene glycol–polycaprolactone (PEG–PCL) nanoparticles, denoted as PEG–PCL@Cur. We employed omics technologies to investigate their impact on melanoma at the molecular level. In vitro studies revealed that PEG–PCL@Cur notably suppressed the growth, movement, and invasiveness of A375 melanoma cells in a dose-dependent manner. Untargeted metabolomics identified 347 metabolites that were significantly altered. A decrease in fumaric acid levels indicated the suppression of oxidative phosphorylation and a shift in metabolism. Proteomics further confirmed the downregulation of key mitochondrial proteins, such as SDHA, pointing to mitochondrial dysfunction. Mechanistically, PEG–PCL@Cur increased reactive oxygen species (ROS) production by raising NADH levels and inhibiting SDHA expression. This led to a reduction in the level of fumaric acid production and a disruption of the tricarboxylic acid (TCA) cycle. Additionally, PEG–PCL@Cur hindered the generation of inorganic phosphate (Pi), resulting in a decreased level of ATP production. These metabolic changes promoted apoptosis and enhanced melanoma cell death. In vivo, PEG–PCL@Cur significantly curtailed tumor growth in a melanoma xenograft model and displayed an enhanced biocompatibility. Histological analysis showed extensive tumor necrosis, diminished proliferation markers, and elevated levels of apoptosis indicators. Overall, our integrated metabolomic and proteomic approach highlights how PEG–PCL@Cur targets SDHA-mediated metabolic reprogramming and mitochondrial dysfunction. This discovery positions PEG–PCL@Cur as a promising nanoplatform for melanoma therapy and offers valuable insights into the development of targeted nanomedicines.

Preparation of curcumin-loaded PCL-PEG-PCL triblock copolymeric nanoparticles by a microchannel technology

Fangyuan Guo,Dingjia Guo,Wei Zhang,Qinying Yan,Yan Yang,Weiyong Hong,Gensheng Yang

Biodegradable polymeric nanoparticles (NPs) have potential therapeutic applications; however, preparing NPs of a specific diameter and uniform size distribution is a challenge. In this work, we fabricated a microchannel system for the preparation of curcumin (Cur)-loaded NPs by the interfacial precipitation method, which rapidly and consistently generated stable NPs with a relatively smaller diameter, narrow size distribution, and higher drug-loading capacity and entrapment efficiency. Poly(ε-caprolactone)-poly(ethylene glycol)-poly (ε-caprolactone) triblock copolymers(PCEC) used as the carrier material was synthesized and characterized. Cur-loaded PCEC NPs had an average size of 167.2   nm with a zeta potential of −   29.23   mV, and showed a loading capacity and drug entrapment efficiency of 15.28%   ±   0.23% and 96.11%   ±   0.13%, respectively. Meanwhile, the NPs demonstrated good biocompatibility and bioavailability, efficient cellular uptake, and long circulation time and a possible liver targeting effect in vivo. These results indicate that the Cur-loaded PCEC NPs can be used as drug carriers in controlled delivery systems and other biomedical applications.

PEG–PCL based micelle hydrogels as oral docetaxel delivery systems for breast cancer therapy

YuJun Wang,LiJuan Chen,LiWei Tan,Qian Zhao,Feng Luo,YuQuan Wei,ZhiYong Qian

In this study, a composite drug delivery system was developed and evaluated for oral delivery of docetaxel: docetaxel-loaded micelles in pH-responsive hydrogel (DTX-micelle–hydrogel). Docetaxel was successfully loaded in micelles with small particle size of 20 nm and high drug loading of 7.76%, which contributed to the drug absorption in the intestinal tract. The experiments of cytotoxicity on 4T1 cells demonstrated the effective antitumor activity of DTX micelles. Meanwhile, a pH-responsive hydrogel was synthesized and optimized for incorporating the docetaxel micelles. The pH-responsiveness and reversibility of the hydrogel were investigated under the pH conditions of the gastrointestinal tract . Furthermore, the DTX-micelle–hydrogel system showed much quicker diffusion of micelles in simulated intestinal fluid than in simulated gastric fluid, which was mainly caused by the change of pH value. The docetaxel released from the micelle–hydrogel system quite slowly, so it had little influence on the absorption of DTX micelles in small intestine . More important, the pharmacokinetic study revealed that the DTX-micelle–hydrogel significantly improved the oral bioavailability of docetaxel (75.6%) about 10 times compared to DTX micelles, and this increase in bioavailability was probably due to the small intestine targeting release of the pH-responsive hydrogel. Consequently, the oral DTX-micelle–hydrogel system was effective in inhibiting tumor growth in subcutaneous 4T1 breast cancer model, and decreased systemic toxicity compared with intravenous treatment. The apoptosis cells in the immunofluorescent studies and the proliferation-positive cells in the immunohistochemical studies were also consistent with the results. Therefore, the DTX-micelle–hydrogel system might be a promising candidate oral drug for breast cancer therapy.

One-pot synthesis and lubricity of fluorescent carbon dots applied on PCL-PEG-PCL hydrogel

Junde Guo,Tangjie Mei,Yue Li,Mahshid Hafezi,Hailin Lu,Jianhui Li,Guangneng Dong

This work presents a method for one-pot synthesis of N-doped nanometer-size carbon dots, which can be assembled with thermosensitive poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) (PCL-PEG-PCL, PCEC) hydrogel to achieve slow-release lubricity. The typical property of this green production was studied by fourier transform infrared (FT-IR), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS) and transmission electron microscope (TEM). The photoluminescence of composite PCEC/CDs hydrogel and its released solutions were characterized by ultraviolet spectrum, and the rheological properties were tested by rotary rheometer. Tribological performance of the released solution from composite PCEC/CDs hydrogel was obtained to compare with PBS and pure CDs solution. The experimental results reveal that the CDs contain the chemical groups of N-H, C–OH/C–O–C and –COOH, etc. In addition, the diameter of the CDs is in the range of 6~8 nm. The phase transition behavior of PCEC/CDs hydrogel can be still kept and its viscoelasticity hydrogel is improved by approximatively 7%. Furthermore, friction coefficient of the released solution from composite PCEC/CDs hydrogel decreases by about 70% than that of PBS. Besides, the wear condition can be improved by a lubricating transfer film formed by released CDs. This novel strategy for slow-release application is valuable for drug delivery and bio-tribology.

Preparation and in vitro/in vivo evaluation of 6-Gingerol TPGS/PEG-PCL polymeric micelles

Lijun Zhen,Qiuyu Wei,Qilong Wang,Huiyun Zhang,Michael Adu-Frimpong,Caleb Kesse Firempong,Ximing Xu,Jiangnan Yu

6-Gingerol, an active herbal ingredient of ginger has various bioactivities such as anti-neurodegenerative disease, anti-inflammatory and so on. The aim of the present study was to enhance the oral bioavailability and brain distribution of 6-Gingerol via polymeric micelles. A polymeric micelles drug delivery system of 6-Gingerol consisting of D-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS) and Poly (ethylene glycol)-poly (ε-caprolactone) (PEG-PCL) was prepared via solvent injection method. The developed 6-Gingerol-loaded TPGS/PEG-PCL micelles (6-GTPMs) were characterized based on particle size, polydispersity index (PDI), zeta potential, encapsulation efficiency (EE), drug loading (DL) and in vitro release profile. The pharmacokinetics and tissue distribution studies were also evaluated. The nanoformulation produced a particle size of 73.24 ± 2.84 nm with acceptable PDI (0.129 ± 0.03), zeta potential (−2.74 ± 0.92 mV), DL (4.64%) and EE (79.68%). The in vitro release profile showed that the 6-GTPMs enhanced the solubility of 6-Gingerol, while the pharmaceutical analysis in rats indicated that 6-GTPMs significantly improved the oral bioavailability of 6-Gingerol (about 3 folds) in circulation. The 6-GTPMs exhibited remarkable brain targetability in the tissue distribution analysis. Collectively, a 6-Gingerol polymeric micelle with enhanced oral bioavailability coupled with excellent brain distribution was successfully developed.

Gambogic acid-loaded PEG–PCL nanoparticles act as an effective antitumor agent against gastric cancer

Dinghu Zhang,Zhengyun Zou,Wei Ren,Hanqing Qian,Qianfeng Cheng,Liulian Ji,Baorui Liu,Qin Liu