共查询到20条相似文献,搜索用时 31 毫秒
1.
由于眼部存在角膜/结膜屏障、血-房水屏障和血-视网膜屏障等,有效的眼部给药依然面临巨大挑战.近年来,温敏水凝胶在眼部给药领域受到了广泛关注.在室温下,温敏水凝胶材料呈液态,便于以局部滴加或玻璃体内注射的方式给药;当与眼部接触升温并超过其临界成胶温度时,能以物理交联的方式快速凝胶化,从而实现原位缓释给药,提高药物生物利用度.在众多温敏水凝胶材料中,合成高分子具有材料和功能多样化等优势,其中较常见的为泊洛沙姆、聚乙二醇/聚酯和聚(N-异丙基丙烯酰胺).本综述首先介绍了以上3类合成高分子基温敏水凝胶材料的制备方法和成胶特性.然后,围绕眼部给药存在的难点,探讨这些温敏水凝胶在治疗角膜病、干眼症、青光眼和眼部炎症等各种眼病中的相关研究进展.最后,我们比较了这3种水凝胶在使用性能上的优缺点,并对未来眼科温敏水凝胶的材料设计提出了设想和展望. 相似文献
2.
Chuanqi Peng Mengxiao Yu Jer‐Tsong Hsieh Payal Kapur Jie Zheng 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2019,131(35):12204-12208
Enhancing tumor targeting of nanocarriers has been a major strategy for advancing clinical translation of cancer nanomedicines. Herein, we report a head‐to‐head comparison between 5 nm renal clearable and 30 nm non‐renal clearable gold nanoparticle (AuNP)‐based drug delivery systems (DDSs) in the delivery of doxorubicin (DOX). While the two DDSs themselves had comparable tumor targeting, we found their different vascular permeability played an even more important role than blood retention in the delivery and intratumoral transport of DOX, of which tumor accumulation, efficacy, and therapeutic index were enhanced 2, 7, and 10‐fold, respectively, for the 5 nm DDS over 30 nm one. These findings indicate that ultrahigh vascular permeability of renal clearable nanocarriers can be utilized to further improve anticancer drug delivery without the need for prolonged blood retention. 相似文献
3.
Chemical Design of Nuclear‐Targeting Mesoporous Silica Nanoparticles for Intra‐nuclear Drug Delivery
《中国化学》2018,36(6):481-486
Targeted drug delivery has been widely explored for efficient tumor therapy with desired efficacy but minimized side effects. It is widely known that large numbers of DNA‐toxins, such as doxorubicin, genes, reactive oxygen species, serving as therapeutic agents, can result in maximized therapeutic effects via the interaction directly with DNA helix. So after cellular uptake, these agents should be further delivered into cell nuclei to play their essential roles in damaging the DNA helix in cancer cells. Here, we demonstrate the first paradigm established in our laboratory in developing nuclear‐targeted drug delivery systems (DDSs) based on MSNs for enhanced therapeutic efficiency in the hope of speeding their translation into the clinics. Firstly, nuclear‐targeting DDSs based on MSNs, capable of intranuclear accumulation and drug release therein, were designed and constructed for the first time, resulting in much enhanced anticancer effects both in vitro and in vivo. Such an MSNs‐based and nuclear‐targeted drug/agent delivery strategy was further applied to overcome multidrug resistance (MDR) of malignant tumors, intra‐nuclearly deliver therapeutic genes, photosensitizers, radio‐enhancement agents and photothermal agents to realize efficient gene therapy, photodynamic therapy, radiation therapy and photothermal therapy, respectively. 相似文献
4.
5.
Soughand Sayadnia Elham Arkan Rana Jahanban‐Esfahlan Sahar Sayadnia Mehdi Jaymand 《先进技术聚合物》2021,32(1):262-271
The drug delivery performances of pH‐responsive magnetic hydrogels (MHs) composed of tragacanth gum (TG), poly(acrylic acid) (PAA), and Fe3O4 nanoparticles (NPs) were investigated in terms of physicochemical as well as biological features. The fabricated drug delivery systems (DDSs) were analyzed using Fourier transform infrared spectroscopy, X‐ray diffraction, vibrating sample magnetometer, scanning electron microscopy, and transmission electron microscopy. The synthesized MHs were loaded with doxorubicin hydrochloride (Dox) as a universal model anti‐cancer drug. The MHs showed excellent Dox loading and encapsulation efficiencies, mainly due to strong hydrogen bonding and electrostatic interaction between the drug and polymeric matrix, as well as porous micro‐structures of the fabricated MHs. The drug‐loaded MHs showed negligible drug release values in physiological condition. In contrast, in cancerous condition (pH 5.0), both MHs exhibited highest drug release values that qualified them as “smart” DDSs. The cytocompatibilities of the MHs as well as the cytotoxicity of the Dox‐loaded MHs were investigated against human epidermoid‐like carcinoma (Hela) cells through MTT assay. In addition, hyperthermia therapy induced by Fe3O4 NPs was applied to locally raise temperature inside the Hela cells at 45 ± 3°C to promote cell death. As a result, the Dox‐loaded MHs can be considered as potential DDSs for chemo/hyperthermia therapy of solid tumors. 相似文献
6.
《中国化学快报》2020,31(5):1051-1059
Drug delivery systems(DDSs) are of paramount importance to deliver drugs at the intended targets,e.g.,tumor cells or tissue by prolonging blood circulation and optimizing the pharmaceutical profiles.However,the therapeutic efficacy of DDSs is severely impaired by insufficient or non-specific drug release.Dynamic chemical bonds having stimuli-liable prope rties are the refore introduced into DDSs for regulating the drug release kinetics.This review summarizes the recent advances of dynamic covalent chemistry in the DDSs for improving cancer therapy.The review discusses the constitutions of the major classes of dynamic covalent bonds,and the respective applications in the tumor-targe ted DDSs which are based on the different responsive mechanisms,including acid-activatable and reduction-activatable.Furthermore,the review also discusses combination strategies of dual dynamic covale nt bonds which can response to the complex tumor microenvironment much more accurately,and then summarizes and analyzes the prospects for the application of dynamic covalent chemistry in DDSs. 相似文献
7.
Wenli Feng Marco Chittò Thomas Fintan Moriarty Guofeng Li Xing Wang 《Macromolecular bioscience》2023,23(1):2200311
The intracellular survival of pathogenic bacteria requires a range of survival strategies and virulence factors. These infections are a significant clinical challenge, wherein treatment frequently fails because of poor antibiotic penetration, stability, and retention in host cells. Drug delivery systems (DDSs) are promising tools to overcome these shortcomings and enhance the efficacy of antibiotic therapy. In this review, the classification and the mechanisms of intracellular bacterial persistence are elaborated. Furthermore, the systematic design strategies applied to DDSs to eliminate intracellular bacteria are also described, and the strategies used for internalization, intracellular activation, bacterial targeting, and immune enhancement are highlighted. Finally, this overview provides guidance for constructing functionalized DDSs to effectively eliminate intracellular bacteria. 相似文献
8.
Hui Liu Jun Zhao Dr. Yufei Xue Dr. Jiaxin Zhang Dr. Hua Bai Prof. Sijun Pan Prof. Bo Peng Prof. Lin Li Prof. Nicolas H. Voelcker 《Angewandte Chemie (International ed. in English)》2023,62(39):e202306100
Drug delivery systems (DDSs) are designed to deliver therapeutic agents to specific target sites while minimizing systemic toxicity. Recent developments in drug-loaded DDSs have demonstrated promising characteristics and paved new pathways for cancer treatment. Light, a prevalent external stimulus, is widely utilized to trigger drug release. However, conventional light sources primarily concentrate on the ultraviolet (UV) and visible light regions, which suffer from limited biological tissue penetration. This limitation hinders applications for deep-tissue tumor drug release. Given their deep tissue penetration and well-established application technology, X-rays have recently received attention for the pursuit of controlled drug release. With precise spatiotemporal and dosage controllability, X-rays stand as an ideal stimulus for achieving controlled drug release in deep-tissue cancer therapy. This article explores the recent advancements in using X-rays for stimulus-triggered drug release in DDSs and delves into their action mechanisms. 相似文献
9.
CAO Mengyao SUN Yueyang XIAO Mingshu LI Li LIU Xiaohui JIN Hong PEI Hao 《高等学校化学研究》2020,36(2):254-260
In spite of great development in nanoparticle-based drug delivery systems(DDSs)for improved therapeutic efficacy,it remains challenging for effective delivery of chemotherapeutic drugs to targeted tumor cells.In this work,we report a triangle DNA origami as targeted DDS for cancer therapy.DNA origami shows excellent biocompatibility and stability in cell culture medium for 24 h.In addition,the DNA origami structures conjugated with multivalent aptamers enable for efficient delivery of anticancer drug doxorubicin(Dox)into targeted cancer cell due to their targeting function,reducing side effects associated with nonspecific distribution.Moreover,we also demonstrated that the multivalent aptamer-modified DNA origami loading Dox exhibits prominent therapeutic efficacy in vitro.Accordingly,this work provides a good paradigm for the development of DNA origami nanostructure-based targeted DDS for cancer therapy. 相似文献
10.
A novel injectable in situ gelling drug delivery system (DDS) consisting of biodegradable N-(2-hydroxyl) propyl-3-trimethyl ammonium chitosan chloride (HTCC) nanoparticles and thermosensitive chitosan/gelatin blend hydrogels was developed for prolonged and sustained controlled drug release. Four different HTCC nanoparticles, prepared based on ionic process of HTCC and oppositely charged molecules such as sodium tripolyphosphate, sodium alginate and carboxymethyl chitosan, were incorporated physically into thermosensitive chitosan/gelatin blend solutions to form the novel DDSs. Resulting DDSs interior morphology was evaluated by scanning electron microscopy. The effect of nanoparticles composition on both the gel process and the gel strength was investigated from which possible hydrogel formation mechanisms were inferred. Finally, bovine serum albumin (BSA), used as a model protein drug, was loaded into four different HTCC nanoparticles to examine and compare the effects of controlled release of these novel DDSs. The results showed that BSA could be sustained and released from these novel DDSs and the release rate was affected by the properties of nanoparticle: the slower BSA release rate was observed from DDS containing nanoparticles with a positive charge than with a negative charge. The described injectable drug delivery systems might have great potential application for local and sustained delivery of protein drugs. 相似文献
11.
Marianna Porcino Xue Li Ruxandra Gref Charlotte Martineau-Corcos 《Molecules (Basel, Switzerland)》2021,26(14)
In the past decades, nanosized drug delivery systems (DDS) have been extensively developed and studied as a promising way to improve the performance of a drug and reduce its undesirable side effects. DDSs are usually very complex supramolecular assemblies made of a core that contains the active substance(s) and ensures a controlled release, which is surrounded by a corona that stabilizes the particles and ensures the delivery to the targeted cells. To optimize the design of engineered DDSs, it is essential to gain a comprehensive understanding of these core–shell assemblies at the atomic level. In this review, we illustrate how solid-state nuclear magnetic resonance (ssNMR) spectroscopy has become an essential tool in DDS design. 相似文献
12.
Nanoscale drug delivery systems (DDSs) have emerged as promising candidates for cancer therapy. However, traditional nanoscale DDSs suffer from several inherent drawbacks, including sophisticated synthesis, uncontrolled structure, low drug loading capacity, high reticuloendothelial system (RES) accumulation, unpredicted metabolic mechanism, and so on. In order to solve these problems, nanodrugs self-assembled from small molecules containing anticancer drugs have received great attention in recent years. Different from traditional nanoscale DDSs, small molecule nanodrugs (SMNs) exhibit unique advantages, such as simple synthesis, defined structure, high drug loading capacity, excellent tumor accumulation and low-toxic metabolism pathway. Hence, with rational design, SMNs can achieve excellent cancer therapeutic efficacy as well as low side effects, extremely promising for the clinic translation. Up to now, significant progress has been made for the exploration of SMNs for cancer therapy. In this review, we briefly summarize the design and synthesis, biological properties, as well as their wide range of applications for cancer therapy. 相似文献
13.
Tumor penetration is important fo r effectively tumor targeting drug delivery.Recently,many researches are published to overcome the barriers that restrict tumor penetration and improve drug delivery efficiency.In the mini review,we first analyzed the barriers influence the tumor penetration,including tumor microenvironment barriers,nanoparticle properties,and interaction barriers between tumor and nanoparticles.To overcome the barrier,several strategies are developed,including modulating tumor microenvironment,changing particle size,transcytosis enabled tumor penetration,cell penetrating peptide modification and overcoming binding site barrier,which could effectively improve tumor penetration,and finally enhance tumor treatment outcome. 相似文献
14.
Stimulator of interferon genes (STING) is an endoplasmic reticulum adaptor transmembrane protein that plays a pivotal role in innate immune system. STING agonists, such as endogenous cyclic dinucleotide (CDN) cyclic GMP-AMP (cGAMP), have been used in diverse clinical research for immunogenic tumor clearance, antiviral treatments and vaccine adjuvants. CDNs containing noncanonical mixed 3′-5′ and 2′-5′ phosphodiester linkages show higher potency in the activation of the STING pathway. In this study, a series of 2′3′-CDNs were designed and synthesized through a modified one-pot strategy. We then established a surface plasmon resonance (SPR)-based binding assay to quantify the binding affinities of synthesized CDNs for human STING, which requested a minuscule amount of sample without any pretreatment. Using this assay, we identified compound 8d (KD = 0.038 μM), a novel CDN that showed higher binding affinity with hSTING than cGAMP (KD = 0.543 μM). Cellular assays confirmed that 8d could trigger the expression of type I IFNs and other proinflammatory cytokines more robust than cGAMP. 8d also exhibited more resistant than cGAMP to enzymatic cleavage in vitro, indicating the successful improvement in drug availability. These findings provide guidelines for the design and structural optimization of CDNs as STING agonists. 相似文献
15.
Kewang Luo Ning Li Wei Ye Hanchao Gao Xinle Luo Baohui Cheng 《Molecules (Basel, Switzerland)》2022,27(14)
Stimulator of interferon gene (STING), an intracellular receptor in the endoplasmic reticulum, could induce the production of cytokines such as type I interferon (IFN) by activating the cGAS-STING signal pathway. In recent years, activation of STING has shown great potential to enhance anti-tumor immunity and reshape the tumor microenvironment, which is expected to be used in tumor immunotherapy. A number of STING agonists have demonstrated promising biological activity and showed excellent synergistic anti-tumor effects in combination with other cancer therapies in preclinical studies and some clinical trials. The combination of STING agonists and ICI also showed a potent effect in improving anti-tumor immunity. In this review, we introduce the cGAS-STING signaling pathway and its effect in tumor immunity and discuss the recent strategies of activation of the STING signaling pathway and its research progress in tumor immunotherapy. 相似文献
16.
Marjan Ghorbani Farideh Mahmoodzadeh Behrooz Jannat Nazila Fathi Maroufi Behnam Hashemi Leila Roshangar 《先进技术聚合物》2019,30(7):1847-1855
Cancer is one of the health problems that lead to death in the world, and nanotechnology was shown to have a unique potential to improve the therapeutic efficacy of anticancer agents. The nanosized drug delivery systems (DDSs) have been offered for targeting tumor tissue because of enhanced drug bioavailability and long circulation time. In this context, we reported a facial approach to prepare a novel pH and glutathione‐responsive nanogel. After that, the nanocarriers coupled with highly fluorescent quantum dots were developed. Then methotrexate (MTX) was loaded into and on the surface of nanogels by ionic interaction so that the triggered MTX release ability of the synthesized nanocarriers was verified through the assessment of in vitro drug release at simulated tumor tissue condition. The improved efficiency of the developed nanogels and their targeted performance via conjugation of MTX (as target ligand of folate receptors) were investigated through the various cell cytotoxicity studies such as 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay, 4′6‐diamidino‐2‐phenylindole (DAPI) staining, and flow cytometry. The results of various cell cytotoxicity studies concluded that the developed smart nanogels have many promising abilities for the targeted MTX delivery to cancer tissues. 相似文献
17.
Dr. Wansang Cho Solchan Won Dr. Yoona Choi Dr. Sihyeong Yi Jong Beom Park Dr. Jun-Gyu Park Caroline E. Kim Dr. Chintam Narayana Ju Hee Kim Dr. Junhyeong Yim Dr. Young Il Choi Prof. Dong-Sup Lee Prof. Seung Bum Park 《Angewandte Chemie (International ed. in English)》2023,62(18):e202300978
Modulating target proteins via the ubiquitin-proteasome system has recently expanded the scope of pharmacological inventions. Stimulator of interferon genes (STING) is an auspicious target for immunotherapy. Seminal studies envisioned the importance of STING as well as the utility of its agonists in immunotherapy outcomes. Herein, we suggest UPPRIS (upregulation of target proteins by protein-protein interaction strategy) to pharmacologically increase cellular STING levels for improved immunotherapy. We discovered the small molecule SB24011 that inhibits STING-TRIM29 E3 ligase interaction, thus blocking TRIM29-induced degradation of STING. SB24011 enhanced STING immunity by upregulating STING protein levels, which robustly potentiated the immunotherapy efficacy of STING agonist and anti-PD-1 antibody via systemic anticancer immunity. Overall, we demonstrated that targeted protein upregulation of STING can be a promising approach for immuno-oncology. 相似文献
18.
Eszter Csizmazia Mária Budai-Szűcs István Erős Zsolt Makai Piroska Szabó-Révész Gábor Varju Erzsébet Csányi 《Journal of Thermal Analysis and Calorimetry》2010,102(1):313-316
Our aim was to develop potential dermal drug delivery systems (DDSs) with a good and lasting moisturizing effect. Lyotropic
liquid crystals (LLCs), gel-emulsions and hydrogels were investigated by means of thermogravimetry, which can give information
about the structure of these preparations, and we could study the water binding mechanisms indirectly in them. We found that
the preparations with a complex structure and strong water bonds hydrate the skin well and lastingly by in vivo tests. Since
the thermoanalytical results correlate with the in vivo test results, this method could be suited for predicting the moisturizing
effect of the vehicles and provide the possibility to select the potential semisolid DDSs for in vivo tests cost and time
effectively. 相似文献
19.
Kui Huang Teresa A. Croce Sharon K. Hamilton Chinessa T. Adkins Billie L. Evans III Eva Harth 《Macromolecular Symposia》2007,255(1):20-23
Summary: The development of suitable delivery systems for intracellular delivery of proteins, peptides and other bioactive materials opens the possibility to establish refined strategies for small drug delivery, gene delivery and vaccination. We present the assembly of advanced drug delivery systems from tailored building blocks to scaffolds and bioactive cargos to afford targeting and transport across biological barriers. In particular, the utilization of novel molecular transporter will advance the bioavailability of small and macromolecular drugs that show targeted intracellular delivery. 相似文献
20.
Atsushi Ikeda Dr. Mai Nagano Motofusa Akiyama Dr. Masashi Matsumoto Sayuri Ito Masaru Mukai Mineo Hashizume Dr. Jun‐ichi Kikuchi Prof. Kiyofumi Katagiri Dr. Takuya Ogawa Dr. Tatsuo Takeya Prof. 《化学:亚洲杂志》2009,4(1):199-205
[70]Fullerene (C70) encapsulated into a surface‐cross‐linked liposome, a so‐called cerasome, was prepared by an exchange reaction incorporating C70?γ‐cyclodextrin complexes into lipid membranes. Fullerene exchange in a cerasome‐incorporated C70 (CIC70), as well as in a lipid‐membrane‐incorporated C70 (LMIC70), was completed within 1 min with stirring at 25 °C. CIC70 was more resistant to lysis than LMIC70 towards lysing agents such as surfactants. Furthermore, the photodynamic activity of CIC70 in HeLa cells was similar to that of LMIC70, indicating that C70 can act as a photosensitizing drug (PS) without release from cerasome membranes. Thus, in contrast with general drug‐delivery systems (DDSs), which require the drug to be released from the interior of liposomes, carriers for PSs for use in photodynamic therapy (PDT) do not necessarily need to release the drug. These results indicate that DDSs with high morphological stability can increase the residence time in blood and achieves tumor‐selective drug delivery by the enhanced permeability and retention (EPR) effect. 相似文献