JOURNAL OF NANOBIOTECHNOLOGY
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2026
·
IF 12.6
Haihan Sun,Jingxin Gou,Xiaoshuang Bi,Jiayin Song,Boyuan Liu,Xiaoyu Jin,Bowen Sui,Xiangqun Jin
Our previous research identified that an oral mPEG- b -PCL polymeric micelle (PM) maintained satisfactory integrity but exhibited limited transcytosis efficiency. To enhance transcytosis and enable ROS-responsive release, we developed a series of hybrid PMs by blending a synthesized L-carnitine-grafted, thioketal-linked LC-PEG 5k -TK-PCL 7k polymer with mPEG 5k -PCL 7k . These hybrid PMs, similar in particle size (120 nm) and drug loading (10%) to the PM composed of pure mPEG 5k -PCL 7k (5-7E), retained good stability in SGF and SIF. However, the hybrid PM with a 40% LC-PEG 5k -TK-PCL 7k proportion showed reduced integrity and penetration in mucus layer. In Caco-2/E12 (7:3) cells, the hybrid PM with a 20% LC-PEG 5k -TK-PCL 7k proportion (20%Hybrid 5-7E) demonstrated superior uptake, low cytotoxicity, and a 3.37-fold higher transcytosis than that of 5-7E. In 4T1 cells, prepared PMs exhibited similar uptake but hybrid PMs showed obvious ROS-responsive dissociation and cytotoxicity. The in vivo integrity and biocompatibility of 20%Hybrid 5-7E were confirmed by plasma concentration and hemolysis test, and the bio-distribution results demonstrated its tumor accumulation. Pharmacokinetics revealed a 10-fold increase in docetaxel (DTX) bioavailability due to the 20%Hybrid 5-7E encapsulation. Consequently, orally administered 20%Hybrid 5-7E (DTX 40 mg/kg) achieved comparable antitumor activity but reduced systemic toxicity relative to intravenously injected DTX solution (10 mg/kg) in 4T1 tumor-bearing BALB/c mice.
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COLLOIDS AND SURFACES B-BIOINTERFACES
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2026
·
IF 5.9
Zishuo Hou,Tianyi Chen,Gangfeng Li,Ronghui Ma,Tengjiao Wang
Near-quantitative polymer functionalization enabled high NO-donor loading. • NO-releasing micelles were not cysteine-responsive, revealing new insights into NO release. • NO-releasing micelles accelerated burn wound healing and promoted vascular regeneration. Burn injuries are often accompanied by severe vascular damage, local tissue hypoxia, and subsequent scar formation. Although nitric oxide (NO) has been widely recognized for its ability to promote angiogenesis and tissue regeneration, achieving sustained NO delivery remains a major challenge. Herein, we developed a formylfuroxan-conjugated NO-releasing micelle (NORM) for burn wound repair. Compared with conventional small-molecule NO donors, the micellar architecture effectively mitigates burst NO release and enables prolonged, sustained NO delivery. In vitro studies demonstrated that NORM exhibits excellent hemocompatibility, minimal cytotoxicity, and a pronounced pro-angiogenic effect. Furthermore, therapeutic evaluation in a murine burn wound model revealed that NORM significantly accelerated wound closure. Collectively, these results demonstrate that sustained NO delivery through NORM effectively promotes vascularized tissue regeneration and highlight its potential as a promising therapeutic strategy for burn wound management. Download: Download high-res image (277KB) Download: Download full-size image
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CHEMICAL ENGINEERING JOURNAL
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2026
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IF 12.5
Li Zhu,Yue Zheng,Mengjuan Yu,Shan Yu,Yiyun Luo,Ravin Narain,Kaihui Nan,Yangjun Chen
Corneal neovascularization (CNV), a major cause of vision impairment, requires improved therapeutic strategies. While Celastrol (Cel), a natural product extracted from traditional Chinese herbs, demonstrates anti-angiogenic potential for CNV treatment, its clinical application can be hindered by poor aqueous solubility and ocular bioavailability. To address this, we developed mucoadhesive micelles using phenylboronic acid (PBA)- and stearic acid (SA)-modified chitosan oligosaccharides (COS) for encapsulation and enhanced ocular delivery of Cel. The Cel-loaded micelles (COSA-PBA@Cel) exhibited a positive Zeta potential of approximately +27 mV, facilitating electrostatic interaction with negatively charged ocular mucin. PBA integration further enabled dynamic covalent bonding with sialic acid residues, synergistically prolonging corneal retention. Therefore, COSA-PBA@Cel nanomicelles exhibited remarkably prolonged ocular surface retention time. In vitro experiments demonstrated that COSA-PBA@Cel micelles effectively inhibited the migration and tube formation of human umbilical vein endothelial cells (HUVECs), showcasing potent anti-neovascular activity. In a mouse model of alkali burn-induced CNV, COSA-PBA@Cel micelles significantly suppressed pathological angiogenesis, primarily through enhanced Cel delivery that modulates the HIF-1α/VEGF signaling pathway. This nanoplatform overcomes key ocular drug delivery challenges while leveraging Cel's therapeutic potential, offering a promising topical solution for CNV management.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Qiao Qiao,Jie Li,Chunying Tao,Meiyang Yang,Weijun Chen,Lipeng Qiu,Huiming Tu
Studies have shown that inflammation is closely linked to the cancer development, and the patients with inflammatory bowel disease (IBD) have a higher risk of colon cancer. Celecoxib (CXB) and camptothecin (CPT) showed potential treatment for IBD and colon cancers, respectively. However, their applications are limited by synchronous delivery, water insolubility, and off-target side effects. Herein, a glutathione (GSH) responsive chondroitin sulfate A (CSA)-SS-CXB micelle loaded with CPT (CSA-SS-CXB@CPT) was prepared as a targeted system to treat colon cancer by anti-inflammatory and antitumor synergistic effect. Specifically, CSA had tumor tumor-targeting effect due to colon cancer lesion-high expression of CD44 receptors. In vitro results verified that CSA-SS-CXB@CPT selectively internalized into colon cancer HT-29 cells and had strong reactive oxygen species (ROS) elimination ability. The CSA-SS-CXB@CPT could rapidly release CXB and CPT in the tumor microenvironment for playing an anti-tumor role. In vivo experiments illustrated that CSA-SS-CXB@CPT significantly targeted tumor tissues and suppressed tumor growth without producing serious side effects in tumor-bearing nude mice. Therefore, this work provides an opportunity for targeted co-delivery of anti-inflammatory and chemotherapy drugs to treat colon cancer.
研究领域:
药学
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肿瘤学
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生物医学工程
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Drug Delivery and Translational Research
·
2019
·Vol. 10
·期 1
·122-135
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IF 3.111
Lu Xiaoyu,Fang Min,Yang Yue,Dai Yu,Xu Jiaqiu,Zhao Di,Lu Yang,Chen Xijing,Lu Shan,Li Ning
PEGylated triacontanol (mPEG 2k -b-TRIA) was developed as a dual-functional polymer with remarkable biocompatibility. The polymer could self-assemble to micelles with critical micelle concentration (CMC) 17.62 μg mL −1 . Docetaxel-loaded mPEG 2k -b-TRIA micelles (DTX PMs) were fabricated to evaluate the feasibility of mPEG 2k -b-TRIA as drug delivery system. DTX PMs achieved desirable particle size of 93.7 nm, drug loading of 6.66%, and drug encapsulation efficiency of 89.87%. The drug release was based on first-order kinetics model, thus enabling prolonged release. Meanwhile, pharmacokinetic study also revealed that DTX PMs could improve the exposure level of DTX and prolong its systemic circulation time. Furthermore, DTX PMs demonstrated significantly enhanced cytotoxicity and cellular uptake in vitro compared with DTX solution. The in vivo tumor inhibition study carried out on MCF-7 bearing BALB/c mice model also validated that DTX PMs exhibited stronger anti-tumor activity but low toxicity. Notably, mPEG 2k -b-TRIA made some contribution to inhibit the growth of breast cancer cells in vitro and in vivo, indicating the potential as anti-tumor complementary agents. All the results suggested that mPEG 2k -b-TRIA polymer as a vehicle in the formulation of anti-cancer drugs may provide an effective way to improve their therapeutic efficacy. Consequently, the mPEG 2k -b-TRIA polymers would be another promising carrier for hydrophobic anti-cancer drugs delivery.
研究领域:
药学
·
肿瘤学
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药物递送系统
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纳米技术
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高影响因子
LANGMUIR
·
2018
·
IF 3.789
Zhihui Qin,Tingting Chen,Wenzhuo Teng,Qiao Jin,Jian Ji
A new class of mixed-charged zwitterionic copolymer poly(aminoethyl methacrylate)-co-poly(methacrylic acid)-co-poly(n-butyl methacrylate) (CPMA) was prepared as drug nanocarrier for efficient intracellular delivery of Doxorubicin (DOX). The mixed-charged CPMA copolymer could readily assemble to micelles in physiological environment (pH 7.4) with the size of 42.6 nm and zeta potential of −26 mV, which would lead to a prolonged circulation time and enhanced tumor penetration. However, the micelles formed large aggregates due to the protonation of carboxyl groups at extracellular tumor pH (pH 6.5). Meanwhile, the zeta potential of CPMA micelles increased from −26 mV to −6 mV when the solution pH was changed from pH 7.4 to pH 6.5. The increase of size and zeta potential at extracellular tumor pH could benefit the retention of micelles in tumor matrix and uptake by cancer cells. The DOX-loaded mixed-charged CPMA micelles could induce a higher internalization at pH 6.5 than 7.4 at varied time periods. Moreover, cytotoxicity assay demonstrated that the blank micelles showed excellent biocompatibility, but were highly cytotoxic toward KB cells after loading with DOX. Thus, the mixed-charged zwitterionic polymeric micelles might be a promising carrier for tumor acidic environment responsive drug delivery.
研究领域:
药剂学
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肿瘤学
·
生物材料
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Pharmaceuticals
·
2025
·Vol. 18
·期 4
·448
·
IF 4.8
Xueli Guo,Zhongyan Liu,Lina Wu,Pan Guo
Background : Liver cancer, especially hepatocellular carcinoma, a prevalent malignant tumor of the digestive system, poses significant therapeutic challenges. While traditional chemotherapy can inhibit tumor progression, its clinical application is limited by insufficient efficacy. Hydrophobic therapeutic agents further encounter challenges including low tumor specificity, poor bioavailability, and severe systemic toxicity. This study aimed to develop a liver-targeted, glutathione (GSH)-responsive micellar system to synergistically enhance drug delivery and antitumor efficacy. Methods : A GSH-responsive disulfide bond was chemically synthesized to conjugate glycyrrhetinic acid (GA) with curcumin (Cur) at a molar ratio of 1:1, forming a prodrug Cur-GA (CGA). This prodrug was co-assembled with glycyrrhizic acid (GL) at a 300% w / w loading ratio into micelles. The system was characterized for physicochemical properties, in vitro drug release in PBS (7.4) without GSH and in PBS (5.0) with 0, 5, or 10 mM GSH, cellular uptake in HepG2 cells, and in vivo efficacy in H22 hepatoma-bearing BALB/c mice. Results : The optimized micelles exhibited a hydrodynamic diameter of 157.67 ± 2.14 nm (PDI: 0.20 ± 0.02) and spherical morphology under TEM. The concentration of CUR in micelles can reach 1.04 mg/mL. In vitro release profiles confirmed GSH-dependent drug release, with 67.5% vs. <40% cumulative Cur release observed at 24 h with/without 10 mM GSH. Flow cytometry and high-content imaging revealed 1.8-fold higher cellular uptake of CGA-GL micelles compared to free drug ( p < 0.001). In vivo, CGA-GL micelles achieving 3.6-fold higher tumor accumulation than non-targeted controls ( p < 0.001), leading to 58.7% tumor volume reduction ( p < 0.001). Conclusions : The GA/GL-based micellar system synergistically enhanced efficacy through active targeting and stimuli-responsive release, providing a promising approach to overcome current limitations in hydrophobic drug delivery for hepatocellular carcinoma therapy.
研究领域:
药剂学
·
肿瘤学
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JOURNAL OF CONTROLLED RELEASE
·
2024
·
IF 10.5
Qiuyu Wei,Chenchen Zhu,Guiping Yuan,Jiahui Jin,Jing Zhang,Wufa Fan,Ying Piao,Shiqun Shao,Sen Lin,Jiajia Xiang,Youqing Shen
Efficient and noninvasive drug delivery for glaucoma therapy necessitates prolonged retention on the ocular surface and deep penetration into the cornea. However, inherent physiological defenses such as rapid tear clearance and low cornea permeability present significant challenges that hinder the effectiveness of trans-corneal drug delivery. In this study, we demonstrate the potential of zwitterionic micelles composed of poly(2-(N-oxide-N,N-diethylamino)ethyl methacrylate)- block -poly(ε-caprolactone) (OPDEA-PCL) amphiphiles as a biocompatible carrier for trans-corneal drug delivery. These micelles exhibit enhanced adhesion to ocular tissues and resistance to tear clearance due to their unique affinity for cell membranes. These characteristics facilitate adsorptive-mediated transcytosis, significantly augmenting trans-corneal transport and intraocular accumulation of the glaucoma medication brinzolamide (BRZ). As a result, OPDEA-PCL/BRZ formulations effectively normalize intraocular pressure in an open-angle glaucoma rat model, surpassing PEGylated and free BRZ formulations. This research underscores the potential utility of OPDEA-PCL micelles as a promising vehicle for noninvasive topical trans-corneal drug delivery in glaucoma therapy.
研究领域:
药剂学
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眼科
·
药物递送系统
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高影响因子
MICROCHEMICAL JOURNAL
·
2026
·
IF 5.2
Zhanghao You,Zhuang Zhang,Hao Zhang,Yuping Shan
Evaluating the impact of stiffness on the entry cell dynamic parameters of micelles at the single-particle level. • The dynamic parameters of TAT and fluorinated TAT interacting with cell membranes was analyzed at single-molecule level. • Visualizing the morphology and structure changes of cell membranes after interacting with TAT and fluorinated TAT. • The mechanical properties of cell membranes were evaluated after interacting with TAT and fluorinated TAT • The effects of FTAT and TAT on the endocytic pathway of micelles was studied. Taking the advantage of unique amphiphilic structure, nanoscale size, and tunable surface, micelles has been a key platform for targeted nano-drug delivery. To enhance the delivery efficiency, regulating the stiffness and modifying the micelles with ligand is necessary. In this study, the effect of stiffness on the dynamic parameters of micelles entry cell was evaluated at single-particle level, the probability for rigid micelles entry cell is higher, but they need larger force and longer duration. The modification of cationic cell-penetrating peptide TAT and its fluorinated derivative (FTAT) could promote the probability of cellular uptake. The promoting effect was further evaluated by measuring the kinetics of TAT and FTAT interacting with cell membrane at single-molecule level. The FTAT could rapidly bind with cell membrane with higher probability, however, it is also easier to detach from cell membrane. These findings can provide insights into optimizing the micelles for targeted nano-drug delivery. Download: Download high-res image (171KB) Download: Download full-size image
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JOURNAL OF DRUG TARGETING
·
2026
·
IF 4.7
Pingping Zhao,Wenhao Yuan,Yuhong Xu,Caifei Jin,Chu Chu,Yan Yang
The transdermal delivery of poorly water-soluble drugs is limited by low aqueous solubility and the stratum corneum permeability barrier. In this study, curcumin was formulated into self-assembled micelles using Tween 20 and polyethylene glycol 400, which exhibited a particle size of 12.5 nm, a zeta potential of −12.5 mV, and a 170-fold increase in solubility. The curcumin micelles (CM) were combined with constant-current iontophoresis (0.45 mA/cm2), to investigate the synergistic enhancement effects and underlying mechanisms. The results showed a 44.2-fold increase in cumulative release over 60 min, with a linear flux–current density relationship (R2 = 0.99). CM exhibited electro-responsive release with an approximate 20-min lag. Under a fixed 2 h total stimulation, pulsed current (4 pulses) nearly doubled the 8-h cumulative release compared to continuous current. Furthermore, both current density and electrode configuration were shown to influence penetration depth and width. Iontophoresis enabled CM to penetrate rat skin to a depth of 270 μm and increased intradermal retention by 258%. In a rat second-degree burn model, the combination therapy significantly accelerated wound healing via promoting angiogenesis, downregulating inflammatory cytokines, and enhancing collagen deposition.
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JOURNAL OF DRUG TARGETING
·
2025
·
IF 3.9
Hong Chen,Michael Adu-Frimpong,Lili Yuan,Yaping Yang,Jollibekov Berdiyar,Jiangnan Yu,Xia Cao,Qilong Wang,Ximing Xu
Astragaloside, a natural flavonol glycoside isolated from plants, exhibits significant tumour-suppressive activity. However, its low solubility and poor bioavailability have hindered its practical application. To improve its bioavailability and therapeutic efficacy, this study prepared Ast-loaded Soluplus/TPGS/Gas hybrid polymer micelles (Ast-STG-M) via the thin-film hydration method. The resulting Ast-STG-M nanoparticles were spherical and uniformly dispersed, characterised by a small particle size (50.92 ± 0.13 nm) and a high encapsulation efficiency (95.24 ± 0.53%). In vitro release profiles demonstrated that the cumulative release rate of Ast from Ast-STG-M was higher than that of free Ast under various pH conditions. After oral administration, compared with free Ast, Ast-STG-M exhibited delayed in vivo elimination and significantly increased bioavailability. Furthermore, results from in vitro and in vivo anti-tumour studies indicated that Ast-STG-M could significantly inhibit the viability of TPC-1 cells, thereby effectively suppressing the growth of solid tumours. In conclusion, Ast-STG-M holds substantial potential as a delivery system for Ast to tumour sites, which not only enhances the oral bioavailability of Ast but also strengthens its anti-cancer activity.
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DRUG DELIVERY
·
2017
·
IF 6.402
Jian Hou,E. Sun,Zhen-Hai Zhang,Jing Wang,Lei Yang,Li Cui,Zhong-Cheng Ke,Xiao-Bin Tan,Xiao-Bin Jia,Huixia Lv
The aim of this study was to establish a paclitaxel (PTX)-loaded mixed micelle delivery system (PTX-TP-M) with vitamin E-TPGS (TPGS) and Plasdone®S-630 Copovidone (PVPS630) as carriers to improve the solubility, oral absorption, and anti-tumor activity of PTX against lung cancer. In this study, PTX-TP-M was prepared using the ethanol thin-film dispersion method followed by characterization of the binary mixed micelles system. The average size of the PTX-TP-M was 83.5 ± 1.8 nm with a polydispersity index of 0.265 ± 0.007 and the drug loading (DL%) and entrapment efficiency (EE%) were 3.09 ± 0.09% and 95.67 ± 2.84%, respectively, which contributed to a high solubility of PTX about 24947-fold increase in water (4.78 ± 0.14 mg/mL). In addition, TEM analysis showed that the PTX-TP-M appeared spherical in structure and was well dispersed without aggregation and adhesion. In vitro release studies showed that the PTX-TP-M displayed a sustained release compared to free PTX in the dialysis bag. The efflux ratio of PTX reduced from 44.83 to 3.52 when formulated as PTX-TP-M; a 92.15% reduction, studied using the Caco-2 monolayer model. The oral bioavailability of PTX also improved by 4.35-fold, suggesting that PTX-TP-M can markedly promote the absorption in the gastrointestinal tract. Using in vitro MTT assays, it was observed that cytotoxicity was markedly increased, and IC50 values of PTX-TP-M (3.14 ± 0.85 and 8.28 ± 1.02 μg/mL) were lower than those of PTX solution (5.21 ± 0.93 and 14.53 ± 1.96 μg/mL) in A549 and Lewis cell, respectively. In vivo anti-tumor studies showed that PTX-TP-M achieved higher anti-tumor efficacy compared with PTX in Lewis bared C57BL/6 mice. Furthermore, a gastrointestinal safety assay also proved the safety of PTX-TP-M. All results demonstrated that the PTX-TP-M exhibited great potential for delivering PTX with increased solubility, oral bioavailability, and anti-cancer activity and this binary mixed micelles drug delivery system has potential to be used clinically.
研究领域:
药学
·
肿瘤学
·
药物递送系统
·
药代动力学
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PubMed
高影响因子
危险品化学品经营许可证（带存储）