INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2015
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IF 3.65
Hailong Zhang,Xiaoyan Huang,Ya Sun,Guangyou Lu,Ke Wang,Zhigang Wang,Jianfeng Xing,Yang Gao
Effects of hydroxypropyl-β-cyclodextrin grafted polyethylenimine (HP-β-CD-PEI) including HP-β-CD-PEI 600 , HP-β-CD-PEI 1800 , HP-β-CD-PEI 10000 on the pulmonary absorption of insulin, calcitonin, 5(6)-carboxyfluorescein (CF) and fluorescein isothiocyanate dextrans (FDs) with various molecular weights (FD4, FD10 and FD70) were examined by an pulmonary absorption study in rats. Pulmonary absorptions of these poorly absorbable drugs were significantly enhanced by HP-β-CD-PEI 1800 and HP-β-CD-PEI 10000 , and HP-β-CD-PEI 1800 with the concentration of 5% (w/v) provided maximal absorption enhancing effect on pulmonary absorption of these model drugs. The toxicity study demonstrated that HP-β-CD-PEI did not induce any toxic action to rat pulmonary membranes. In addition, zeta potential of insulin solution changed to positive by addition of various HP-β-CD-PEI, meanwhile, the degree of positive charge was linearly correlated with absorption enhancing effect of HP-β-CD-PEI, suggesting that positive charge of HP-β-CD-PEI might be related to their absorption enhancing mechanisms for enhancing pulmonary absorption of insulin in rats. In conclusion, HP-β-CD-PEI is a potential and safe absorption enhancer for improving absorption of hydrophilic macromolecules especially peptide and protein drugs by pulmonary delivery.
研究领域:
药理学
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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
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2017
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IF 7.786
Lei Wu,Min Liu,Wei Shan,Xi Zhu,Lijia Li,Zhirong Zhang,Yuan Huang
Ligand-functionalization can increase the affinity of nanoparticles (NPs) with targeted cells. However, one major defect of ligands still exists in oral administration: limited receptor recognition. The hindrance of mucus network and deactivation of enzymes severely challenge the targeting efficiency of macromolecular ligands. Inspired by “molecular exchange” between intestinal microbiota and host cells, we anchored microbiota metabolite butyrate on classical “mucus-inert” polyethylene glycol (PEG) NPs. Butyrate has unique advantages of low molecule weight, high hydrophilicity and chemical stability. Interestingly, in vitro mucus-permeability and in vivo mucus distribution of PEG NPs were not impaired by butyrate-functionalization. Enhanced cellular uptake was achieved via specific interaction between butyrate and the monocarboxylate transporter (MCT) on cell membranes , which subsequently ameliorated transepithelial transport and intestinal absorption in the ileum. In vitro safety assessment validated the non-toxicity of butyrate-modification. Finally, insulin-loaded Bu-PEG NPs generated a stronger hypoglycemic response on diabetic rats and 2.87-fold higher oral bioavailability compared with bare PEG NPs. This study demonstrated that butyrate-functionalization could improve the intestinal absorption of macromolecules by overcoming multiple obstacles in the gastrointestinal tract, providing a promising active targeting strategy for oral administration.
研究领域:
药剂学
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生物医学工程
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肠道微生物组学
✓ 已验证
DOI
PubMed
高影响因子
Asian Journal of Pharmaceutical Sciences
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2023
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IF 10.2
Yuting Li,Liyun Xing,Lingling Wang,Xi Liu,Licheng Wu,Mingjie Ni,Zhou Zhou,Lian Li,Xiuxiu Liu,Yuan Huang
Exosomes, as promising vehicles, have been widely used in the research of oral drug delivery, but the generally low drug loading efficiency of exosomes seriously limits its application and transformation. In this study, we systematically investigated the effects of drug loading methods and physicochemical properties (lipophilicity and molecular weight) on drug loading efficiency of milk-derived exosomes to explore the most appropriate loading conditions. Our finding revealed that the drug loading efficiency of exosomes was closely related to the drug loading method, drug lipophilicity, drug molecular weight and exosome/drug proportions. Of note, we demonstrated the universality that hydrophilic biomacromolecule drugs were the most appropriate loading drugs for milk-derived exosomes, which was attributed to the efficient loading capacity and sustained release behavior. Furthermore, milk-derived exosomes could significantly improve the transepithelial transport and oral bioavailability of model hydrophilic biomacromolecule drugs (octreotide, exendin-4 and salmon calcitonin). Collectively, our results suggested that the encapsulation of hydrophilic biomacromolecule drugs might be the most promising direction for milk exosomes as oral drug delivery vehicles.
研究领域:
药理学
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纳米医学
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药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Science
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2024
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IF 5.8
Yicheng Jiang,Li Mi,Xiang Xu,Adric Ru Khiing Hii,Zhenghong Wu,Xiaole Qi
Destruction of insulin caused by the gastric microenvironment and rapid deactivation pose inevitable barriers to oral macromolecular absorption, especially for most peptide and protein drugs. In this study, we developed high-density sodium alginate microspheres composed of magnesium oxide and urease to address these challenges. These microspheres aim to anchor the gastric mucus layer and induce microenvironmental liquefaction, thereby enhancing gastric retention and the protection of insulin. The sedimentation test confirmed the capability of the Ins/Ur/MgO@SA microsphere to rapidly traverse the gastric juice under the influence of gravity. Additionally, the urease immobilized on the Ins/Ur/MgO@SA microspheres catalyzes the hydrolysis of urea in the gastric mucus and promotes the liquefaction of mucus, which is beneficial for microsphere retention. The inclusion of MgO particles and urease, acting as pHM modifiers, helps in adjusting the local pH to avoid gastric acid-induced damage. Subsequently, an in vivo pharmacokinetic experiment verified that the relative bioavailability of the p.o. Ins/Ur/MgO@SA treated group was 15-fold higher than that of the p.o.insulin treated group. Meanwhile, satisfactory blood glucose level (BGL) reduction was observed in diabetic animals. In conclusion, Ins/Ur/MgO@SA microspheres demonstrate high biocompatibility as insulin carriers with prolonged drug release time and increased gastric retention properties, showing a far-reaching strategy for oral macromolecular drug delivery.
研究领域:
药学
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药物递送系统
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生物技术
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
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2024
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IF 13.3
Xinyue Zhang,Ye He,Zhiqi Wang,Ying Zhang,Wen Guo,Shuai Li,Xinyu Wang,Yuling Mao,Siling Wang
To further develop intracellular delivery systems of macromolecular drugs, understanding the cracking mechanisms and drug release behaviors of environment-responsive carriers, as well as their intrinsic linkages, is essential for achieving personalized or diversified delivery of macromolecular drugs. Herein, we designed a class of degradable dendritic mesoporous nanoparticles (DDMSNs), utilizing very large cavities and tetrasulfide bonds in the skeleton to achieve high drug loading and release within tumor cells. To comprehensively understand and develop intracellular drug delivery systems, this study delved deeper into the delivery of tetrasulfide-bonded DDMSNs, including chemical reactions, cracking kinetics, and release kinetics. First, the drug release of the DDMSNs within the cytoplasm was closely related to the chemical reaction of tetrasulfide bonds. Thus, based on experiments, the oxidation–reduction mechanism of tetrasulfide-bonded DDMSNs was explained, and the relationship was elaborated between cracking and drug release of the DDMSNs with different sulfur contents. To further explore this relationship, the cracking behavior, drug-loading capacity and release capacity of the DDMSNs was investigated with the different sulfur contents in different simulated environments, and in MDA-MB-231 cancer cells. Inspired by the reaction kinetic calculations, we analyzed the cracking and drug release behavior of the DDMSNs, and ultimately achieved dual cracking secondary drug release of the carriers by controlling the content of sulfur elements. Here, we report improved biomedical materials for advanced, customized, and intentional intracellular delivery of therapeutic macromolecules, in which theoretical calculations and experimental components were combined to study the mechanism of drug release influenced by carrier cracking, providing essential guidance for designing advanced drug delivery systems through a chemical engineering method.
研究领域:
药学
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纳米技术
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生物医学工程
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化学工程
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）