1.Effect of exosomes as drug carriers in chemotherapy of pancreatic cancer.
Journal of Central South University(Medical Sciences) 2023;48(2):268-274
Pancreatic cancer (PC) is a malignant tumor of the digestive tract with poor patient prognosis. The PC incidence is still increasing with a 5-year survival rate of only 10%. At present, surgical resection is the most effective method to treat PC, however, 80% of the patients missed the best time for surgery after they have been diagnosed as PC. Chemotherapy is one of the main treating methods but PC is insensitive to chemotherapy, prone to drug resistance, and is accompanied by many side effects which are related to a lack of specific target. Exosomes are nanoscale vesicles secreted by almost all cell types and can carry various bioactive substances which mediate cell communication and material transport. They are characterized by a low immunogenicity, low cytotoxicity, high penetration potential and homing capacity, and possess the potential of being used as advanced drug carriers. Therefore, it is a hot research topic to use drug-loaded exosomes for tumor therapy. They may alleviate chemotherapy resistance, reduce side effects, and enhance the curative effect. In recent years, exosome drug carriers have achieved considerable results in PC chemotherapy studies.
Humans
;
Exosomes/metabolism*
;
Drug Carriers/metabolism*
;
Pancreatic Neoplasms/diagnosis*
;
Antineoplastic Agents/therapeutic use*
2.Application of organic nanocarriers for intraocular drug delivery.
Wanwan CHANG ; Jingjing SHEN ; Zhuang LIU ; Qian CHEN
Journal of Zhejiang University. Medical sciences 2023;52(3):259-266
The application of intraocular drug delivery is usually limited due to special anatomical and physiological barriers, and the elimination mechanisms in the eye. Organic nano-drug delivery carriers exhibit excellent adhesion, permeability, targeted modification and controlled release abilities to overcome the obstacles and improve the efficiency of drug delivery and bioavailability. Solid lipid nanoparticles can entrap the active components in the lipid structure to improve the stability of drugs and reduce the production cost. Liposomes can transport hydrophobic or hydrophilic molecules, including small molecules, proteins and nucleic acids. Compared with linear macromolecules, dendrimers have a regular structure and well-defined molecular mass and size, which can precisely control the molecular shape and functional groups. Degradable polymer materials endow nano-delivery systems a variety of size, potential, morphology and other characteristics, which enable controlled release of drugs and are easy to modify with a variety of ligands and functional molecules. Organic biomimetic nanocarriers are highly optimized through evolution of natural particles, showing better biocompatibility and lower toxicity. In this article, we summarize the advantages of organic nanocarriers in overcoming multiple barriers and improving the bioavailability of drugs, and highlight the latest research progresses on the application of organic nanocarriers for treatment of ocular diseases.
Drug Carriers
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Delayed-Action Preparations
;
Drug Delivery Systems
;
Nanoparticles/chemistry*
3.Research progress on the nucleoside/nucleotide-loaded nanomedicines.
Zheng ZHOU ; Haifang LIU ; Mingzhou YE
Journal of Zhejiang University. Medical sciences 2023;52(3):279-284
Nucleoside drugs play an essential role in treating major diseases such as tumor and viral infections, and have been widely applied in clinics. However, the effectiveness and application of nucleoside drugs are significantly limited by their intrinsic properties such as low bioavailability, lack of targeting ability, and inability to enter the cells. Nanocarriers can improve the physiological properties of nucleoside drugs by improving drug delivery efficiency and availability, maintaining drug efficacy and system stability, adjusting the binding ability of the carrier and drug molecules, as well as modifying specific molecules to achieve active targeting. Starting from the design strategy of nucleoside drug nanodelivery systems, the design and therapeutic effect of these nanomedicines are described in this review, and the future development directions of nucleoside/nucleotide-loaded nanomedicines are also discussed.
Nanomedicine
;
Nucleosides/chemistry*
;
Nucleotides
;
Nanoparticles/chemistry*
;
Drug Delivery Systems
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Drug Carriers
4.Advances in anti-invasive fungal drug delivery systems.
Zhongyi MA ; Xinyu WANG ; Chong LI
Journal of Zhejiang University. Medical sciences 2023;52(3):318-327
Currently, the first-line drugs for invasive fungal infections (IFI), such as amphotericin B, fluconazole and itraconazole, have drawbacks including poor water solubility, low bioavailability, and severe side effects. Using drug delivery systems is a promising strategy to improve the efficacy and safety of traditional antifungal therapy. Synthetic and biomimetic carriers have greatly facilitated the development of targeted delivery systems for antifungal drugs. Synthetic carrier drug delivery systems, such as liposomes, nanoparticles, polymer micelles, and microspheres, can improve the physicochemical properties of antifungal drugs, prolong their circulation time, enhance targeting capabilities, and reduce toxic side effects. Cell membrane biomimetic drug delivery systems, such as macrophage or red blood cell membrane-coated drug delivery systems, retain the membrane structure of somatic cells and confer various biological functions and specific targeting abilities to the loaded antifungal drugs, exhibiting better biocompatibility and lower toxicity. This article reviews the development of antifungal drug delivery systems and their application in the treatment of IFI, and also discusses the prospects of novel biomimetic carriers in antifungal drug delivery.
Antifungal Agents/therapeutic use*
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Drug Delivery Systems
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Amphotericin B/therapeutic use*
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Liposomes/chemistry*
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Nanoparticles
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Drug Carriers
5.Factors affecting nasal drug delivery and design strategies for intranasal drug delivery.
Xiaoyun HU ; Xiao YUE ; Chuanbin WU ; Xuejuan ZHANG
Journal of Zhejiang University. Medical sciences 2023;52(3):328-337
Intranasal drug delivery system is a non-invasive drug delivery route with the advantages of no first-pass effect, rapid effect and brain targeting. It is a feasible alternative to drug delivery via injection, and a potential drug delivery route for the central nervous system. However, the nasal physiological environment is complex, and the nasal delivery system requires "integration of medicine and device". Its delivery efficiency is affected by many factors such as the features and formulations of drug, delivery devices and nasal cavity physiology. Some strategies have been designed to improve the solubility, stability, membrane permeability and nasal retention time of drugs. These include the use of prodrugs, adding enzyme inhibitors and absorption enhancers to preparations, and new drug carriers, which can eventually improve the efficiency of intranasal drug delivery. This article reviews recent publications and describes the above mentioned aspects and design strategies for nasal intranasal drug delivery systems to provide insights for the development of intranasal drug delivery systems.
Administration, Intranasal
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Drug Delivery Systems
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Pharmaceutical Preparations
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Drug Carriers
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Brain
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Nasal Cavity/physiology*
;
Nasal Mucosa
6.Research progress on vesicles from Chinese medicinal herbs.
Junyan LI ; Wenping WANG ; Yi ZHANG ; Zhizhong YANG
Journal of Zhejiang University. Medical sciences 2023;52(3):349-360
Vesicles derived from Chinese medicinal herbs (VCMH) are nano-vesicular entities released by the cells of Chinese medicinal herbs. VCMHs have various biological effects and targeting characteristics, and their component chemicals and functional activities are closely related to the parent plant. VCMH differs from animal-derived vesicles in three ways: stability, specificity, and safety. There are a number of extraction and isolation techniques for VCMH, each with their own benefits and drawbacks, and there is no unified standard. When two or more approaches are used, high quantities of intact vesicles can be obtained more quickly and efficiently. The obtained VCMHs were systematically examined and evaluated. Firstly, they are generally saucer-shaped, cup-shaped or sphere, with particle size of 10-300 nm. Secondly, they contain lipids, proteins, nucleic acids and other active substances, and these components are an important part for intercellular information transfer. Finally, they mostly have good biocompatibility and low toxicity, with anti-inflammatory, antioxidant, anti-tumor and anti-fibrotic effects. As a new drug carrier, VCMHs have outstanding active targeting capabilities, and the capsule form can effectively preserve the drugs, considerably enhancing drug delivery efficiency and stability in vitro and in vivo. The modification of its vesicular structure by suitable physical or chemical means can further create more stable and precise drug carriers. This article reviews the extraction and purification techniques, activity evaluation and application of VCMH to provide information for further research and application of new active substances and targeted drug carriers.
Animals
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Drugs, Chinese Herbal/chemistry*
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Plants, Medicinal
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Antioxidants
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Anti-Inflammatory Agents
;
Drug Carriers
7.Mechanism of Der f 1/IGF-1 nanoparticle promoting the production of regulatory T cell.
Longpeng MA ; Xiangqian LUO ; Lihua MO ; Jialiang FAN ; Dabo LIU
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2023;37(4):272-277
Objective:To prepare PLGA nanoparticles loaded with Der f 1/IGF-1(Der f 1/IGF-1 NPs) and investigate their role in promoting the formation of Treg cells. Methods:NPs coated with Der f 1/IGF-1 were prepared by double emulsion method and their physicochemical properties and cumulative release rate in vitro were analyzed. After pretreatment, BMDC was divided into Saline group, Blank NPs group, Der f 1/IGF-1 group and Der f 1/IGF-1 NPs group. Determination of the expression of IL-10 and TGF-β in BMDC by ELISA. The number of Treg cells was detected by flow cytometry. Results:The results showed that Der f 1/IGF-1 NPs were spherical structures, with good dispersion, particle size less than 200 nm, negative charge and stable slow-release effect of Zeta potential. After BMDC pretreatment, the expression levels of TGF-β and IL-10 in BMDC cells in the Der f 1/IGF-1 NPs group were significantly increased compared with the Blank NPs group, and the difference was statistically significant(P<0.001). After co-culture with CD4+ T cells, the proportion of Treg cells produced in the Der f 1/IGF-1 NPs group was significantly increased, and the difference was statistically significant(P<0.001). Conclusion:Der f 1/IGF-1 NPs can induce Treg cell generation in vitro. This study provides a new and more effective method for the reconstruction of immune tolerance dysfunction.
Humans
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T-Lymphocytes, Regulatory/metabolism*
;
Interleukin-10/metabolism*
;
Insulin-Like Growth Factor I
;
Transforming Growth Factor beta
;
Nanoparticles/chemistry*
;
Particle Size
;
Drug Carriers/chemistry*
8.Advances in modification and delivery of nucleic acid drugs.
Junfeng WANG ; Manman TAN ; Ying WANG ; Xiangrui LIU ; Aifu LIN
Journal of Zhejiang University. Medical sciences 2023;52(4):417-428
Nucleic acid-based drugs, such as RNA and DNA drugs, exert their effects at the genetic level. Currently, widely utilized nucleic acid-based drugs include nucleic acid aptamers, antisense oligonucleotides, mRNA, miRNA, siRNA and saRNA. However, these drugs frequently encounter challenges during clinical application, such as poor stability, weak targeting specificity, and difficulties in traversing physiological barriers. By employing chemical modifications of nucleic acid structures, it is possible to enhance the stability and targeting specificity of certain nucleic acid drugs within the body, thereby improving delivery efficiency and reducing immunogenicity. Moreover, utilizing nucleic acid drug carriers can facilitate the transportation of drugs to lesion sites, thereby aiding efficient intracellular escape and promoting drug efficacy within the body. Currently, commonly employed delivery carriers include virus vectors, lipid nanoparticles, polymer nanoparticles, inorganic nanoparticles, protein carriers and extracellular vesicles. Nevertheless, individual modifications or delivery carriers alone are insufficient to overcome numerous obstacles. The integration of nucleic acid chemical modifications with drug delivery systems holds promise for achieving enhanced therapeutic effects. However, this approach also presents increased technical complexity and clinical translation costs. Therefore, the development of nucleic acid drug carriers and nucleic acid chemical modifications that are both practical and simple, while maintaining high efficacy, low toxicity, and precise nucleic acid delivery, has become a prominent research focus in the field of nucleic acid drug development. This review comprehensively summarizes the advancements in nucleic acid-based drug modifica-tions and delivery systems. Additionally, strategies to enhance nucleic acid drug delivery efficiency are discussed, with the aim of providing valuable insights for the translational application of nucleic acid drugs.
Nucleic Acids
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RNA, Small Interfering/genetics*
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Drug Carriers
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Drug Delivery Systems
;
Drug Development
9.Preparation of vitexin albumin nanoparticles and its pharmacokinetic study.
Xue ZHANG ; Qiang WANG ; Jian-Quan PAN ; Si-Wei WANG ; Cheng-Yuan WU ; Yun-Na CHEN ; Feng-Ling WANG ; Lei WANG ; Wei-Dong CHEN
China Journal of Chinese Materia Medica 2023;48(19):5205-5215
This study aims to prepare vitexin albumin nanoparticles(VT-BSA-NPs) to alleviate the low bioavailability of vitexin(VT) in vivo due to its poor water solubility. VT micro powders were prepared by the antisolvent crystallization method, and the morphology, size, and physicochemical properties of VT micro powders were studied. The results showed that the VT micro powder had a particle size of(187.13±7.15) nm, an approximate spherical morphology, and a uniform size distribution. Compared with VT, the chemical structure of VT micro powders has not changed. VT-BSA-NPs were prepared from VT micro powders by desolvation-crosslinking curing method. The preparation process was screened by single factor test and orthogonal test, and the quality evaluation of the optimal prescription particle size, PDI, Zeta potential, EE, and morphology was performed. The results showed that the average particle size of VT-BSA-NPs was(124.33±0.47) nm; the PDI was 0.184±0.012; the Zeta potential was(-48.83±2.20) mV, and the encapsulation rate was 83.43%±0.39%, all of which met the formulation-related requirements. The morphological results showed that the VT-BSA-NPs were approximately spherical in appearance, regular in shape, and without adhesion on the surface. In vitro release results showed a significantly reduced release rate of VT-BSA-NPs compared with VT, indicating a good sustained release effect. LC-MS/MS was used to establish an analytical method for in vivo analysis of VT and study the plasma pharmacokinetics of VT-BSA-NPs in rats. The results showed that the specificity of the analytical method was good, and the extraction recovery was more than 90%. Compared with VT and VT micro powders, VT-BSA-NPs could significantly increase AUC, MRT, and t_(1/2), which was beneficial to improve the bioavailability of VT.
Rats
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Animals
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Serum Albumin, Bovine/chemistry*
;
Chromatography, Liquid
;
Tandem Mass Spectrometry
;
Nanoparticles/chemistry*
;
Particle Size
;
Drug Carriers/chemistry*
10.Research progress of coarse-grained molecular dynamics in drug carrier materials.
Minquan ZHANG ; Mingcheng GONG ; Jin WANG ; Zhenhua CHEN ; Liangliang ZHOU
Journal of Biomedical Engineering 2023;40(4):799-804
As one of the traditional computer simulation techniques, molecular simulation can intuitively display and quantify molecular structure and explain experimental phenomena from the microscopic molecular level. When the simulation system increases, the amount of calculation will also increase, which will cause a great burden on the simulation system. Coarse-grained molecular dynamics is a method of mesoscopic molecular simulation, which can simplify the molecular structure and improve computational efficiency, as a result, coarse-grained molecular dynamics is often used when simulating macromolecular systems such as drug carrier materials. In this article, we reviewed the recent research results of using coarse-grained molecular dynamics to simulate drug carriers, in order to provide a reference for future pharmaceutical preparation research and accelerate the entry of drug research into the era of precision drug design.
Molecular Dynamics Simulation
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Drug Carriers

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