ACS Nano
·
2023
·
IF 17.1
Yiyang Guo,Yubin Ma,Xin Chen,Min Li,Xuehu Ma,Gang Cheng,Changying Xue,Yi Y. Zuo,Bingbing Sun
The penetration behavior of nanoparticles in mucous depends on physicochemical properties of the nanoparticles and the mucus microenvironment, due to particle–mucin interactions and the presence of the mucin mesh space filtration effect. To date, it is still unclear how the surface properties of nanoparticles influence their mucus penetration behaviors in various physiological and pathophysiological conditions. In this study, we have prepared a comprehensive library of amine-, carboxyl-, and PEG-modified silica nanoparticles (SNPs) with controlled surface ligand densities. Using multiple particle tracking, we have studied the mechanism responsible for the mucus penetration behaviors of these SNPs. It was found that PEG- and amine-modified SNPs exhibited pH-independent immobilization under iso-density conditions, while carboxyl-modified SNPs exhibited enhanced movement only in weakly alkaline mucus. Biophysical characterizations demonstrated that amine- and carboxyl-modified SNPs were trapped in mucus due to electrostatic interactions and hydrogen bonding with mucin. In contrast, high-density PEGylated surface formed a brush conformation that shields particle–mucin interactions. We have further investigated the surface property-dependent mucus penetration behavior using a murine airway distribution model. This study provides insights for designing efficient transmucosal nanocarriers for prevention and treatment of pulmonary diseases.
研究领域:
生物医学工程
·
药剂学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2025
·
IF 5.2
Yiyao Li,Huixian Tian,Han Zeng,Yu Zhang,Tian Yin,Haibing He,Jingxin Gou,Xing Tang
Oral delivery of peptide and protein drugs (PDs) is hindered by the impermeable intestinal mucosa, which consists of both the mucus layer and the epithelium. Therefore, double-layer (mucus layer and epithelium) overcoming nanocarriers need to be designed to enhance the transporting efficiency of PDs. However, the requirements for surface properties to penetrate these two barriers are quite distinct. In this study, nanoparticles (NPs) with balanced mucus permeation and cellular uptake were developed by modulating surface properties to improve the endocytosis efficiency of exenatide (EXT). The EXT-loaded ovolecithin (Lipoid E 80)/dextran/bovine serum albumin (EDB) NPs, solidified by sodium trimetaphosphate (STMP), were prepared through double emulsification combined with interfacial crosslinking solidification. The EDB NPs were then coated with cationic polyelectrolyte chitosan (CS) shell to form CS-EDB NPs, which exhibited 83.50 ± 0.44 % of encapsulation efficiency (EE), a particle size of approximately 277.0 ± 3.96 nm, and a Zeta potential of −16.2 ± 0.71 mV. Compared to uncoated EDB NPs, CS-EDB NPs showed a 1.1-fold reduction in mucus penetration (P app ), as measured using the Transwell mucus-penetrating model. However, CS-EDB NPs demonstrated a 2.15-fold and 1.77-fold increase in cellular uptake and transepithelial transport efficiency across a Caco-2/E-12 co-culture model, respectively, primarily driven by energy-dependent endocytosis and partially mediated by macropinocytosis. Furthermore, CS-EDB NPs achieved 13.29 % of pharmacological bioavailability and effectively regulated blood glucose, serum lipid levels, and improved islet function upon long-term administration. In conclusion, the core–shell structured CS-EDB NPs successfully protected against the harsh gastrointestinal tract (GIT) environment, providing improved endocytosis efficiency by slightly compromising mucus penetration while significantly enhancing cellular uptake, offering a promising approach for the oral delivery of PDs.
研究领域:
药剂学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2025
·
IF 11.5
Yameng Wang,Zhiyuan Wang,Qibin Li,Yangjun Feng,Jinling Li,Yuxiang Lu,JingYing Zhang,Xue Ke
The special physiological barriers of women, such as vaginal mucus and self-cleaning behavior, pose great challenges for the treatment of vulvovaginal candidiasis ( VVC ), and the drug resistance caused by fungal biofilms limits the application of existing antifungal drugs. Based on this, we designed a “three-in-one” thermosensitive gel system (AF/BP Gel) loaded with antibiofilm nanoparticles (AF NPs) and mucus penetration-assisting nanoparticles (BP NPs) to achieve vaginal adhesion while enhancing mucus and biofilm penetration. AF NPs were loaded with farnesol (FAR) and amphotericin B (AMB), and FAR is one of quorum sensing molecules which can interfere with biofilm-related genes such as ALS3 , HWP1 , RAS1 , CPH1 , EFG1 , NRG1 , TUP1 , UME6 , and disperse mature biofilm, thus playing a synergic antibiofilm role with AMB. BP NPs was loaded with bromelain (BRO), which cleared the mucus barrier for AF NPs and help it penetrate deep into the infection. These two kinds of nanoparticles use the thermosensitive gel matrix to reach the surface of the vaginal mucosa uniformly and persistently to overcome the obstacle of vaginal self-cleaning. AF/BP Gel showed great anti- candida albicans activity in vitro and in vivo , and greatly improved the inflammatory conditions in VVC mice. Overall, this “three-in-one” thermosensitive gel system can overcome multiple physiological barriers and resist different periods of biofilm, providing a new platform for treating vagina-associated infections.
研究领域:
药剂学
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微生物学
·
妇科学
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产品关联
DOI
PubMed
高影响因子
Biomolecules
·
2022
·Vol. 12
·期 9
·1263
·
IF 6.064
Dengchao Xie,Xin Zhou,Bo Xiao,Lian Duan,Zhenhua Zhu
Oral nanoparticles have been considered a prospective drug delivery carrier against ulcerative colitis (UC). To enhance the mucus-penetrating capacity and aqueous solubility, and strengthen the anti-inflammatory effect of resveratrol (RSV), we fabricated RSV-loaded silk fibroin-based nanoparticles with the functionalization of Pluronic F127 (PF-127). The obtained PF-127-functionalized RSV-loaded NPs had an average particle size around 170 nm, a narrow size distribution (polydispersity index < 0.2), and negative zeta potential (−20.5 mV). Our results indicated that the introduction of PF-127 strengthened the mucus-penetrating property of NPs. In vitro studies suggested that NPs with PF-127 enhanced the suppression of the secretion of proinflammatory cytokine TNF-α and reactive oxygen species (ROS) from RAW 264.7 macrophages under lipopolysaccharide stimulation in comparison with other counterparts. According to the evaluation of macro symptoms and main inflammatory cytokines, we further report preferable therapeutic outcomes achieved by PF-127 functionalized-NP-treated dextran sulphate sodium (DSS) groups in the colitis model compared with blank silk fibroin NPs and RSV-loaded NPs without the functionalization of PF-127. Taken together, this work suggests that the fabricated PF-127 NPs via the oral route are promising and useful RSV-loaded nanocarriers for UC treatment.Keywords:silk fibroin;resveratrol;nanoparticles;ulcerative colitis
研究领域:
药学
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纳米技术
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炎症
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药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Research
·
2024
·
IF 8.5
Chunxi Shu,Wei Zhang,Yiwei Zhang,Yu Li,Xinbo Xu,Yanan Zhou,Yue Zhang,Qin Zhong,Cong He,Yin Zhu,Xiaolei Wang
Helicobacter pylori colonizes over 50% of people worldwide. Biofilm formation through penetrating gastric mucus and resistance acquired by H. pylori markedly reduces the efficacy of traditional antibiotics. The present triple therapy and bismuth-based quadruple therapy inevitably causes intestinal flora disturbance and fails to address the excessive H. pylori-triggered inflammatory response. Herein, a mucus-permeable therapeutic platform (Cu-MOF@NF) that consists of copper-bearing metal-organic framework (Cu-MOF) loaded with nitrogen-doped carbon dots and naturally active polysaccharide fucoidan is developed. The experimental results demonstrate that Cu-MOF@NF can penetrate the mucus layer and hinder H. pylori from adhering on gastric epithelial cells of the stomach. Notably, released Cu2+ can degrade the polysaccharides in the biofilm and interfere with the cyclic growing mode of “bacterioplankton ↔ biofilm”, thereby preventing recurrent and persistent infection. Compared with traditional triple therapy, the Cu-MOF@NF not only possesses impressive antibacterial effect (even include multidrug-resistant strains), but also improves the inflammatory microenvironment without disrupting the balance of intestinal flora, providing a more efficient, safe, and antibiotic-free new approach to eradicating H. pylori.
研究领域:
生物医学工程
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微生物学
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药学
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材料科学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2019
·
IF 7.901
Pengyu Li,Xiaonan Chen,Yuanna Shen,Huatian Li,Yiqing Zou,Gang Yuan,Ping Hu,Haiyan Hu
The resistance of Helicobacter pylori ( H. pylori ) to conventional antibiotic treatments becomes prevalent recently. The biofilm formation was found to be highly correlated with the antibiotic resistance of H. pylori in the last decades. Moreover, H. pylori colonizes on the digestive tract epithelium located under the mucus layers, which further reduces therapeutic efficacy as mucus layers trap and remove exogenous substances including drugs. Herein, we reported a novel lipid polymer nanoparticles (LPNs) to overcome both biofilm and mucus layers obstruction. LPNs employed chitosan nanoparticle (CS NPs) as the core, mixed lipid layer containing rhamnolipids (RHL) as the shell and the surface of LPNs was further modified with DSPE-PEG2000 to improve hydrophilicity. Clarithromycin (CLR), a first-line drug for H. pylori infection, was encapsulated in LPNs. LPNs, especially the formulation utilizing 100% of RHL as the lipid shell, exhibited excellent eradicating ability to H. pylori biofilm, which was mainly reflected in the significant reduction of biofilm biomass and viability, destruction of biofilm architecture and elimination of extracellular polymeric substances (EPS). The anti-biofilm activities of LPNs are related to: 1) the disrupting effect of RHL on biofilm matrix; 2) antibacterial effects of CLR and CS NPs on biofilm bacteria and 3) inhibitory effects of CS NPs and RHL on bacteria adhesion and biofilm formation. Furthermore, PEGylated LPNs could rapidly penetrate through mucus without interacting with mucins and effectively eradicate H. pylori biofilm under mucus layer. In conclusion, a novel approach of drug-containing LPNs that could penetrate through mucus layers and effectively eradicate H. pylori biofilm provides new ways to treat persistent H. pylori infections.
研究领域:
药剂学
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微生物学
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纳米技术
·
胃肠病学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2024
·
IF 10.5
Hezhi Wang,Ye Yuan,Lu Qin,Mengmeng Yue,Jingwen Xue,Zhixiang Cui,Xuanguang Zhan,Jiayi Gai,Xin Zhang,Jian Guan,Shirui Mao
Faced with the threat of lung cancer-related deaths worldwide, small interfering RNA (siRNA) can silence tumor related messenger RNA (mRNA) to tackle the issue of drug resistance with enhanced anti-tumor effects. However, how to increase lung tumor targeting and penetration with enhanced gene silencing are the issues to be addressed. Thus, the objective of this study is to explore the feasibility of designing non-viral siRNA vectors for enhanced lung tumor therapy via inhalation. Here, shell-core based polymer-lipid hybrid nanoparticles (HNPs) were prepared via microfluidics by coating PLGA on siRNA-loaded cationic liposomes (Lipoplexes). Transmission electron microscopy and energy dispersive spectroscopy study demonstrated that HNP consists of a PLGA shell and a lipid core. Atomic force microscopy study indicated that the rigidity of HNPs could be well tuned by changing thickness of the PLGA shell. The designed HNPs were muco-inert with increased stability in mucus and BALF, good safety, enhanced mucus penetration and cellular uptake. Crucially, HNP1 with the thinnest PLGA shell exhibited superior transfection efficiency (84.83%) in A549 cells, which was comparable to that of lipoplexes and Lipofectamine 2000, and its tumor permeability was 1.88 times that of lipoplexes in A549-3T3 tumor spheroids. After internalization of the HNPs, not only endosomal escape but also lysosomal exocytosis was observed. The transfection efficiency of HNP1 (39.33%) was 2.26 times that of lipoplexes in A549-3T3 tumor spheroids. Moreover, HNPs exhibited excellent stability during nebulization via soft mist inhaler. In conclusion, our study reveals the great potential of HNP1 in siRNA delivery for lung cancer therapy via inhalation.
研究领域:
药学
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纳米技术
·
癌症研究
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生物医学工程
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药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2020
·
IF 4.845
Yue Zhou,Ning Gu,Fang Yang
Organic and inorganic nanomaterials have shown great potential in drug delivery applications due to their unique physical and chemical properties. Orally administered nanoparticles have attracted great attention because it is acceptable, convenient, and safe. However, nanoparticles need to overcome numerous hurdles such as acidic gastric environment, the continuous secretion of mucus, and fast gastric emptying after being delivered via an oral route. Here, we used a stimuli-responsive and triggered release strategy for superparamagnetic iron oxide nanoparticles (SPIONPs)-loaded gastro-retentive tablets for in situ bubbles generation. These materials realize SPIOs controlled release and delivery specific to the stomach. The tablet formulation contains a foaming agent (sodium bicarbonate, NaHCO 3 ), adhesive component (HPMC/carbomer 934 P (1:1)), filler (lactose/mannitol (10:1)) and SPIONPs. The in vitro bubble generation and SPIONPs released from the tablets were characterized. The ex vivo gastric adhesive ability, acoustic stimuli performance, and tissue penetration were further evaluated. The results show that when the fabricated tablets interacted with the acidic microenvironment, the carbon dioxide (CO 2 ) could be generated and be captured by ultrasound (US) imaging. Simultaneous with bubble production, SPIONPs are released from the tablets to further control ultrasound-mediated force and deliver SPIONPs entering through the mucus layer. The SPIONPs were loaded in the tablets and could be released in a controllable way; thus, the magnetic resonance imaging (MRI) could also be used to monitor the tablet status and SPIONP delivery process. Therefore, SPIONPs-loaded gastro-retentive effervescent tablets offer effective release and absorption of nanoparticles in the gastric area and be imaged by MRI and US.
研究领域:
药学
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纳米技术
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药物递送系统
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nano Today
·
2020
·
IF 16.907
Xinqi Cai,Yiting Xu,Lina Zhao,Jiamei Xu,Shengkai Li,Chaoqi Wen,Xin Xia,Qian Dong,Xiaoxiao Hu,Xiaofeng Wang,Long Chen,Zhuo Chen,Weihong Tan
Gastric environment is an extreme pH and enzyme-rich condition, which together with gastric mucus barrier and short retention time of oral medicine militate against effective oral drug delivery to lesion areas of gastric diseases. Assembly, especially shape-control assembly of magnetic nanoparticles potentially helps the site-selective drug molecule delivery. However, the harsh gastric condition, and cumbersome and strict requirements make the in situ reversible assembly remain challenging. Herein, synergistically pepsin-bridged and magnetic field-mediated morphological control of magnetic-graphitic-nanocapsules (MGNs) needle assembly (MNA) is developed in stomach for prolonged gastric retention and enhanced mucus penetration. The MNAs with good biocompatibility, large magnetic moments and unique needle-shape are formed with the help of pepsin , demonstrating superior magnetic-driven capability to overcome gastric mucus barrier. Molecular dynamics simulations reveal binding modes between MGN and amino acid residues on either side of the pepsin, indicating pepsin acts as “bridge” allowing sufficient contact among MGNs and further facilitates the needle assembly. Moreover, anticancer drug doxorubicin (DOX)-loaded MNAs demonstrate superior targeted cancer cell killing ability and boosted DOX penetration in a mouse model, which promises good bioavailability of drug molecules. The versatile MNA-based platform offers a robust strategy for effective oral drug delivery and site-selective therapy of gastric diseases.
研究领域:
药学
·
纳米技术
·
生物医学工程
·
药物递送系统
✓ 已验证
产品关联
DOI
高影响因子
ACS Applied Materials & Interfaces
·
2023
·
IF 9.5
Chen Zhang,Zhao Zhao,Yi-Jun Jia,Peng-Qi Zhang,Yun Sun,Yong-Can Zhou,Gao-Xue Wang,Bin Zhu
Viral diseases have constantly caused great threats to global public health, resulting in an urgent need for effective vaccines. However, the current viral vaccines often show low immunogenicity. To counter this, we report a smart strategy of a well-designed modular nanoparticle (LSG-TDH) that recapitulates the dominant antigen SG, low-molecular-weight protamine, and tetralysine-modified H-chain apoferritin (TDH). The constructed LSG-TDH nanovaccine could self-assemble into a nanocage structure, which confers excellent mucus-penetrating, cellular affinity, and uptake ability. Studies demonstrate that the LSG-TDH nanovaccine could strongly activate both mucosal and systemic immune responses. Importantly, by immunizing wild-type and TLR2 knockout (TLR2-KO) zebrafish, we found that TLR2 could mediate LSG-TDH-induced adaptive mucosal and systemic immune responses by activating antigen-presenting cells. Collectively, our findings offer new insights into rational viral vaccine design and provide additional evidence of the vital role of TLR2 in regulating adaptive immunity.
研究领域:
病毒学
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免疫学
·
纳米技术
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2019
·
IF 2.606
Xin Zhou,Yao Liu,Yamei Huang,Ya Ma,Jun Lv,Bo Xiao
Oral nanotherapeutics have been proven to have great potential in the treatment of ulcerative colitis (UC). However, their therapeutic efficacies are mainly restricted by the lack of mucus-penetrating capacity. To overcome this obstacle, we functionalized the surface of curcumin (CUR)-loaded polymeric nanoparticles (NPs) with various amounts of pluronic F127 (PF127). The obtained NPs (NPs-I, NPs-II, NPs-III and NPs-IV) had hydrodynamic particle sizes around 250 nm with highly monodisperse size distributions, negatively charged surfaces and constant CUR release properties. It was found that the functionalization with PF127 notably improved the mucus-penetrating ability of NPs. Further cell experiments revealed that they showed negative cytotoxicities, and PF127-functionalized NPs (NPs-II, NPs-III and NPs-IV) yielded remarkably higher internalization rates of CUR in macrophages as compared to NPs without PF127 modification (NPs-I). Interestingly, NPs-III exhibited notably stronger capacity to decrease the secretion of TNF-α from macrophages when they were compared with other NPs. Finally, mouse experiments demonstrated that NPs-III achieved the best therapeutic efficacy against UC among all the tested NPs. Our results clearly suggest that PF127-functionalized polymeric NPs with desirable compositional proportions are promising and efficient nanotherapeutics for UC therapy.
研究领域:
药学
·
纳米技术
·
胃肠病学
✓ 已验证
产品关联
DOI
高影响因子
Advanced Healthcare Materials
·
2025
·
IF 9.6
Shali Tan,Ruijue Dan,Junfeng Guo,Qinglin Wei,Kaige Xu,Qiang Luo,Yuchen Zhang,Chaoqiang Fan,Xiaoyan Zhao,Donghui Zhu,Quan Wang,Malcolm Xing,Shiming Yang,Yu Huang
Helicobacter pylori ( H. pylori ) infection remains a major challenge in gastric disease treatment, with conventional antibiotic therapies hindered by poor gastric retention, lack of specificity, and the growing threat of bacterial resistance. To address these limitations, we introduce a novel bioengineered robotic system inspired by icebreakers, integrating multi-functional nanomaterials for targeted, autonomous, and efficient H. pylori eradication. Our micro-robots combine a platinum nanozyme-based calcium carbonate complex with chitosan (Cs) modification, gastric epithelial cell membranes (CM) coating, and pronase (P) incorporation, enabling selective targeting and autonomous motility. Upon gastric acid exposure, this system undergoes controlled decomposition, generating carbon dioxide to propel movement, releasing pronase to penetrate and degrade mucus barriers, and deploying Pt nanozymes for deep bacterial eradication. This multi-modal mechanism significantly enhances gastric retention, precision targeting, and therapeutic effectiveness. Our in vitro and in vivo studies validate its superior antibacterial activity, biocompatibility, and its unprecedented ability to mitigate H. pylori -induced inflammation while preserving intestinal microbiota balance. By combining bioengineering, nanotechnology, and autonomous propulsion, this innovation represents a paradigm shift in H. pylori therapy, offering a precise, efficient, and resistance-mitigating alternative to conventional treatments.
研究领域:
纳米医学
·
生物医学工程
·
微型机器人
·
胃肠病学
·
抗菌治疗
·
药物递送
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）