EUROPEAN POLYMER JOURNAL
·
2024
·
IF 5.8
Longxin Lin,Yaling Zheng,Caixia Huang,Lanlan Cai,Hua Zhang,Wen Xu,Xiaoying Wang,Wei Xu
Oral drug delivery with tumor-targeting treatment persists as a challenge. In this study, a mixed polymeric micelle (PM) delivery system was designed to overcome the barriers to oral administration for tumor-targeting delivery of paclitaxel (PTX) for breast cancer treatment. D-α-Tocopheryl polyethylene glycol 1000 succinate-modified carboxymethyl chitosan-rhein (TCR) conjugate and Biotin-polyethylene glycol 2000-Biotin (BPB) conjugate were mixed to form TCR-BPB PMs. The particle size and polydispersity index of optimized PTX-loaded TCR-BPB PMs (PTX/TCR-BPB PMs) was 195.90 ± 7.63 nm and 0.08 ± 0.00, with a drug-loading capacity of 41.94 ± 2.47 %. In simulated gastroenteric fluid and blood environments, the PMs presented a sustained-release manner. PTX/TCR-BPB PMs were taken up by Caco-2 and 4T1 cells and displayed strong cytotoxicity in a time- and concentration-dependent manner. PTX/TCR-BPB PMs significantly improved intestinal absorption of PTX. The pharmacokinetics, tissue distribution, and in vivo imaging indicated that PTX/TCR-BPB PMs could enhance oral bioavailability of PTX, prolong the retention time of PTX in the blood, and enhance PTX tumor-targeting ability. PTX/TCR-BPB PMs enhance the antitumor efficacy of PTX and reduce its toxicity in normal organs. Therefore, TCR-BPB PMs are expected to serve as delivery carriers for the oral and tumor-targeting delivery of hydrophobic antitumor drugs.
研究领域:
药剂学
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肿瘤学
·
生物材料
✓ 已验证
产品关联
DOI
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2019
·
IF 3.973
Wen Yao Hu,Zhi Min Wu,Qian Qian Yang,Yue Jin Liu,Juan Li,Can Yang Zhang
The development of intelligent oral drug delivery carrier aiming at efficiently bring insulin to intestine is of great significance for diabetes mellitus therapy. In the present study, a series of amphiphilic pH-sensitive block copolymer poly(methyl methacrylate- co -methacrylicacid)- b -poly(2-amino ethyl methacrylate) [P(MMA- co -MAA)- b -PAEMA] was synthesized via activators regenerated by electron transfer atom transfer radical polymerization (ARGET ATRP) and further self-assembled into pH-responsive cationic polymeric micelles (PCPMs) for oral insulin delivery. The structure and molecular weight were confirmed by proton nuclear magnetic resonance ( 1 H-NMR), Fourier transforming infrared spectrum (FT-IR) and gel permeation chromatography (GPC), respectively. The critical micelle concentration (CMC) values of these copolymers were measured by fluorescent probe method at pH 1.2 (8–15 μg/mL) and pH 7.4 (22–42 μg/mL), respectively, demonstrating high stability at acidic environment. A decrease in the particle size of PCPMs was associated with an increased pH at beginning, which reached around 200 nm at neutral pH, while the particle size increased obviously with pH increase, indicating the pH-sensitivity of PCPMs. The insulin was entrapped into the core of PCPMs (Ins-loaded PCPMs) with high loading efficiency via diafiltration method. The in vitro experiments show Ins-loaded PCPMs have low toxicity and exhibit pH-triggered release profile with remitted initial burst release. The results indicate that the PCPMs self-assembled from P(MMA- co -MAA)- b -PAEMA may be potential carriers for efficient oral delivery of insulin with controlled release property.
研究领域:
药剂学
·
生物材料
·
糖尿病治疗
✓ 已验证
DOI
高影响因子
ACS Applied Nano Materials
·
2024
·
IF 5.3
Rujing Xu,Ying Lu,Mengxiao Liu,Yanzhao Yin,Junsheng Zhao,Lin Wu,Song Shen
Oral delivery of insulin exhibits low bioavailability due to the hydrolysis in acidic gastric juice, biodegradation of enzymes, and inefficient penetration through the intestinal mucus and epithelial cell layer. Here, we report a micelle platform to enhance the oral delivery of insulin. Insulin was precipitated by zinc ions to form hydrophobic nanoparticles and subsequently coated with a surfactant polysorbate-80 (Tween-80) to form nanosized micelles (TW-Zn-rhINS). Tween-80 protects the insulin from the degradation of enzymes, meanwhile facilitating the diffusion within mucus and the epithelial cell layer by opening the tight junctions. The micelles were then lyophilized and encapsulated in enteric capsules to overcome acidic hydrolysis in gastric juice. The micelles significantly increased transcellular insulin transport and uptake. The in vivo experiments demonstrated that oral TW-Zn-rhINS micelle capsules (30 IU/kg) decreased the blood glucose of diabetic mice by 58.74% after administration for 6 h, while the postprandial blood glucose dropped by 51.1%. Pharmacokinetics data indicated that the relative oral bioavailability of TW-Zn-rhINS was 7.88%, which was 7.73 times higher than that of insulin. The micelles present a promising platform to enhance the oral bioavailability of insulin, also indicating a potential for oral delivery of protein.
研究领域:
药剂学
·
生物医学工程
·
药物代谢动力学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2025
·
IF 11.5
Wanting Dai,Xiaoxiao Song,Rui Wang,Weiwei He,Junyi Yin,Shaoping Nie
Selenium deficiency associated with a high risk of many diseases remains a global challenge. Owing to the narrow margin between “nutrition-toxicity” doses of selenium, it is imperative to achieve accurate selenium supplement. Nano‑selenium (SeNPs) is a novel form of selenium supplement with low toxicity, but it could be trapped and removed by intestinal mucus, thus limiting its oral delivery. The mucus penetration of SeNPs is highly associated with interactions between SeNPs and mucin (the structural component of mucus). In this study, we selected four polysaccharides with different functional groups and molecular weights, i.e. chitosan oligosaccharide (COS), chitosan (CS), chitosan quaternary ammonium salt (HACC), and carboxymethyl cellulose (CMC) as templates to modify SeNPs. Then we systematically explored the non-covalent interactions between polysaccharides stabilized nano-Se (PS-SeNPs) and mucin, determined and examined mucus penetration behavior and mechanism of different PS-SeNPs by coarse-grained molecular dynamics simulations, both in vitro and in vivo . It could be observed that penetration of PS-SeNPs depends on their distinct surface properties and mucus pH conditions. COS-SeNPs with short oligosaccharide chains accumulated and bridged with mucin, hindering its mucus penetration at pH 7.4. While HACC-SeNPs with NH 3 + and N + exhibited high binding affinity with mucin, inducing its mucus penetration. The negatively charged CMC-SeNPs diffused freely in mucus due to their electrostatic-repelled interaction and hydrophobic interaction with mucin. This study establishes a theoretical foundation for precise application of SeNPs in oral administration and offers valuable insights into the precise utilization of polysaccharides as tailored carriers of nanoparticles in mucus-covered tissues.
研究领域:
生物医学工程
·
药剂学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2020
·
IF 4.321
Xinyi Tan,Na Yin,Zixu Liu,Rong Sun,Jingxin Gou,Tian Yin,Yu Zhang,Haibing He,Xing Tang
The oral delivery of macromolecules using nanoparticles is limited by secreted mucus, resulting in low contact or internalization via intestinal cells and, thus, both mucus trapping and further low cellular uptake need to be overcome. Here, hydrophilic and electroneutral nanoparticles were developed to overcome mucus trapping and enhance the oral delivery of macromolecules. Mesoporous silica nanoparticles (MSNs) were synthesized and modified with a hydrophilic block polymer (poly(lactic acid)–methoxy poly(ethylene glycol), PLA–PEG), and then an overall electroneutrality and promoted cellular uptake were achieved by sequential modification with cell-penetrating peptides (CPPs). Reduced hydrophobic and electrostatic interactions of MSN@PLA–PEG-CPP with mucus decreased mucus trapping by 36.0%, increased the cellular uptake of MSN@PLA–PEG-CPP by 2.3-folds in mucous conditions via active heparan sulfate proteoglycan receptor (HSPG)-mediated and caveolae-mediated endocytosis and electrostatic interactions. Furthermore, insulin, a model macromolecular drug, was successfully loaded into the nanoparticles (INS@MSN@PLA–PEG-CPP). Compared with insulin solution, in vitro cellular uptake in mucous conditions and in vivo pharmacodynamic effects were significantly increased by 9.1- and 14.2-folds, respectively. As well, all nanoparticles with or without insulin loading presented negligible in vitro and in vivo toxicity. Herein, hydrophilic and electroneutral nanoparticles with sequential PEG and CPP modification could promote cellular uptake against mucus trapping and finally show good prospects for oral insulin delivery.
研究领域:
药剂学
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生物医学工程
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF DRUG TARGETING
·
2018
·
IF 3.408
Liping Zhang,Yanan Shi,Yina Song,Dongyu Duan,Xuemei Zhang,Kaoxiang Sun,Youxin Li
Safe and effective oral delivery of peptide is a challenge. Here, we used exenatide and zinc ions (Zn2+) to form a complex to explore a meaningful oral-targeted drug-delivery system. Polyethylene glycol-poly(lactic acid-co-glycolic acid) (PEG-PLGA) was used to prepare nanoparticles (NPs) to escape the degradation caused by gastrointestinal enzymes. Transferrin (Tf) was used as a targeting group. PEG-PLGA-NPs and Tf-modified exenatide-Zn2+-loaded NPs (Tf-PEG-PLGA-NPs) were uniformly sized spheres according to transmission electron microscopy. The results of pharmacodynamic and pharmacokinetic investigations in vivo were consistent with in vitro studies using Caco-2 cells. Tf enhanced NPs transport in cell-uptake and transmembrane-transport experiments. Our results showed that the relative bioavailability of Tf-exenatide-Zn2+-NPs was higher than that of exenatide-Zn2+-NPs. The relative bioavailability of Tf-exenatide-Zn2+-NPs versus subcutaneous injection of exenatide was 6.45%. This was a preliminary exploration of the oral administration of exenatide, that data from which can be used for future investigations.
研究领域:
药剂学
·
生物医学工程
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
FOOD HYDROCOLLOIDS
·
2019
·
IF 5.839
Yun-shan Wei,Kun Feng,Min-hua Zong,Hong Wu
To improve the bioavailability of lactoferrin (Lf) and achieve its controlled release in the intestinal tract, a pH-responsive composite system for the oral delivery of Lf was successfully developed for the first time. The negatively charged poly(lactide-co-glycolide) (PLGA)/poly(styrene-co-4-styrene-sulfonate) (PSS) nanoparticles (NPs) were firstly prepared by solvent displacement, and the resulting NPs were spherical in shape with diameter of around 120 nm and zeta potential of −50.7 mV. Then, the positively charged Lf was incubated with PLGA/PSS NPs followed by coating with pectin to improve the Lf adsorption efficiency. The Lf adsorption efficiency decreased with the increase of Lf concentration, but it was even as high as 80.5% when Lf concentration was 8.0 mg/mL. The pectin coated Lf-PLGA/PSS NPs were further incorporated into Eudragit S-100 (ES-100) micro-capsule by the self-assembly method and the obtained composite ES-100 micro-capsule was found to be spherical with an average diameter of 2.22 μ m. The in vitro release experiment showed that only a little Lf (<1%) was released from micro-capsule in simulated gastric fluid comparing with that of pectin coated Lf-PLGA/PSS NPs (30%), and around 82% Lf was released into the simulated intestinal tract in the following 8 h. The results of cytotoxicity test suggested that there was negligible toxicity of the composite micro-capsule against Caco-2 cells. The SDS-PAGE and CD spectrum analysis indicated that the micro-encapsulated Lf retained the integrity of its primary and secondary structure during the heating treatment process. Hence, the obtained Lf-loaded composite micro-capsule is promising in the oral delivery of Lf.
研究领域:
药剂学
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Runan Zhao,Tao Chen,Shumeng Hu,Xuesong Chi,Songfeng Yu,Yanfei Li,Wenjun Wang,Beiwei Zhu,Donghong Liu,Jiangning Hu
Inflammatory bowel disease (IBD) management is often hindered by limited efficacy and significant systemic side effects of traditional oral medications, owing to their lack of targeted delivery and multifunctional capabilities. This study introduces a novel orally sequence-targeted delivery system, QT-CMOF@HAS nanocube, based on hydrophobic cross-linked CD-MOF (CMOF) for the precise delivery of quercetin (Qu) to the inflamed colonic lesions. To enhance the mitochondrial targeting capabilities of Qu, a mitochondrial-functionalized Qu-(5-carboxypentyl) (triphenyl) phosphonium bromide (TPP) precursor complex (QT) was initially synthesized and loaded into the CMOF. A chitosan/glutathione-responsive hyaluronic acid (HAS) shell was subsequently coated onto the CMOF, forming the QT-CMOF@HAS nanoplatform to further enhance the gastrointestinal tolerance. Our results demonstrated that QT-CMOF@HAS significantly alleviated colitis symptoms by modulating the repolarization of pro-inflammatory M1 macrophages to anti-inflammatory M2 phenotypes and deactivation of the TLR4/MyD88/NF-κB pathway, thus reducing the production of inflammatory cytokines. Furthermore, the integrity of the intestinal mucosal barrier and the gut microbiota were enhanced. This study highlights the potential of QT-CMOF@HAS nanocube as a promising therapeutic tool for IBD treatment, offering a multifaceted approach to tackle inflammation and support mucosal healing in a targeted and controlled manner.
研究领域:
药剂学
·
炎症研究
·
纳米医学
✓ 已验证
产品关联
DOI
高影响因子
Advanced Healthcare Materials
·
2024
·
IF 10
Jinfan Yang,Ning Shang,Zhengqing Li,Ji Xu,Xin Zhou,Hui Zhou,Wen Luo,Peng Xu,Yucheng Zhou,Xueru Sheng,Zheng Zhu,Mingzhen Zhang,Xiaojun Ma,Mingqian Tan,Hao Wu
Oral formulation is the ideal treatment method for inflammatory bowel disease (IBD) therapy, but the mucosal damage and diarrhea symptoms impede the drug retention around the inflammatory region, severely limiting IBD therapeutic efficacy. To address this, an oral astaxanthin (Ast) precise delivery formulation is developed with the selective Ast anchoring around the inflammatory region by the novel lactoferrin (LF)-responsive flocculation. This formulation also heightens the apparent solubility of Ast with the minimized edible safety risks for the edible raw materials. For in vivo IBD therapy, the precise delivery formulation exhibits remarkable outcomes, including a significant increase in colon length and a 100% survival rate. Furthermore, it is verified that the mechanism of treatment is primarily attributed to the improved immunoregulation, epithelial repair, and gut microbiota remodeling after the LF-responsive flocculation. This effective inflammatory-responsive delivery design is instructive and valuable to develop more precise delivery systems for IBD therapy.
研究领域:
药剂学
·
生物医学
·
消化系统疾病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Polymers
·
2024
·Vol. 16
·期 16
·2368
·
IF 4.7
Bukatuka Futila Clemence,Lin Xiao,Guang Yang
In this study, a novel oral formulation of berberine hydrochloride (BBH) hydrogel was successfully synthesized through physical cross-linking using chitosan (CS) and carboxymethyl-β-cyclodextrin (CMCD). The characterization results confirmed the successful synthesis of the CS/CMCD hydrogel and the subsequent loading of BBH into this composite (CS/CMCD/BBH) was effectively accomplished. The BBH was used as a model drug and the resulting hydrogel demonstrated a sustained drug release profile. In addition to its improved solubility and sustained release characteristics, the hydrogel exhibited excellent antibacterial activity against common pathogens such asEscherichia coli(E. coli),Staphylococcus aureus(S. aureus), andCandida albicans(C. albicans). Additionally, in vitro studies indicated that the hydrogel was not cytotoxic to NIH3T3 and HaCaT cells, suggesting its safety for biomedical applications. This lack of cytotoxic effects, combined with the mechanical strength, solubility improvements, and antibacterial properties of the hydrogel, positions the CS/CMCD/BBH hydrogel as a promising candidate for the effective oral delivery of BBH. By addressing the solubility and delivery challenges of BBH, this hydrogel offers a viable solution for the oral administration of BBH, with potential applications in various biomedical fields.
研究领域:
药剂学
·
生物材料学
·
微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD RESEARCH INTERNATIONAL
·
2025
·
IF 8
Jingbo Liu,Yang Liu,Shanglin Li,LongJiang Tian,Yajuan Li,Chunmei Liu,Sitong Ma,Ting Zhang,Meng Yang,Zhiyang Du
Efficient oral coassembly strategies have attracted increasing attention for the preferable co-delivery of multiple nutraceuticals. Inspired by superior transport tendencies of the intestinal glucose transporter 2 (GLUT2) to fructose-modified biopolymers, this study fabricated the coassemblies consisting of fructose-modified chitosan (Fru-CS) shell and disulfonic acid-modified γ-cyclodextrin (BA-γ-CD) core to effectively co-deliver hydrophilic egg white oligopeptides (EWOP) and hydrophobic curcumin (Cur). The non-covalent interactions-driven coassemblies exhibited the admirable nanoscale colloidal features and nutraceuticals (EWOP/Cur) co-loading capacity (20.6–25.5 > > 10 %). Besides, the coassemblies introduced the outstanding application synergism (> 15 % enhancement) to nutraceuticals under multi-dimensional scenarios ( e.g. , digestion, heat, UV-light, and antioxidant). Notably, the outer Fru-CS-coated coassemblies could dramatically improve the intact absorption efficiency (2.5–7.9 times) of nutraceuticals mainly via GLUT2-oriented transcytosis and cooperate with BA-γ-CD to achieve better gastrointestinal retention and mucus permeation. This work offers a facile and effective co-assembly strategy for oral co-delivery of nutraceuticals for food processing and healthcare.
研究领域:
食品科学
·
营养学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
·
2016
·
IF 3.773
Yashu Yao,Mengxin Xia,Huizhen Wang,Guowen Li,Hongyi Shen,Guang Ji,Qianchao Meng,Yan Xie
A novel nanogel/gel based on chitosan (CS) for the oral delivery of myricetin (Myr) was developed and evaluated comprehensively. The particle size of the obtained Myr-loaded CS/β-glycerol phosphate (β-GP) nanogels was in the range of 100–300 nm. The rheological tests showed that the sol-gel transition happened when the nanogels were exposed to physiological temperatures, and 3D network structures of the gelatinized nanogels (gels) were confirmed by Scanning Electron Microscopy. Myr was released from CS/β-GP nanogel/gel in acidic buffers via a Fickian mechanism, and this release was simultaneously accompanied by swelling and erosion. Moreover, the nanogel/gel exhibited no cytotoxicity by MTT assay, and the oral bioavailability of Myr in rats was improved with an accelerated absorption rate after Myr was loaded into CS/β-GP nanogel/gel. In summary, all of the above showed that CS/β-GP nanogel/gel was an excellent system for orally delivering Myr.
研究领域:
药剂学
·
生物材料学
✓ 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）