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Since the application of biomedical nanotechnology in the field of drug delivery breathes new life into the research and development of high-end innovative agents, a substantial number of novel nano-drug delivery systems (nano-DDSs) have been successively developed and applied in the clinical practice. Among them, small molecule pure drug and prodrug-based nanoassemblies have grasped great attention, owing to the facile fabrication, ultrahigh drug loading and feasible industrial production. Herein, we provide an overview on the latest updates of small-molecule nanoassemblies. Firstly, the self-assembled prodrug-based nano-DDSs are introduced, including nanoassemblies formed by amphiphilic monomeric prodrugs, hydrophobic monomeric prodrugs and dimer monomeric prodrugs. Then, the recent advances on nanoassemblies of small molecule pure chemical drugs and biological drugs are presented. Furthermore, carrier-free small-molecule hybrid nanoassemblies of pure drugs and/or prodrugs are summarized and analyzed. Finally, the rational design, application prospects and clinical challenges of small-molecule self-assembled nano-DDSs are discussed and highlighted. This review aims to provide scientific reference for constructing the next generation of nanomedicines.
ABSTRACT
Molecular dynamics simulation technology relies on Newtonian mechanics to simulate the motion of molecular system of the real system by computer simulation. It has been used in the research of self-assembly processes illustration and macroscopic performance prediction of self-assembly nano-drug delivery systems (NDDS) in recent years, which contributes to the facilitation and accurate design of preparations. In this review, the definitions, catalogues, and the modules of molecular dynamics simulation techniques are introduced, and the current status of their applications are summarized in the acquisition and analysis of microscale information, such as particle size, morphology, the formation of microdomains, and molecule distribution of the self-assembly NDDS and the prediction of their macroscale performances, including stability, drug loading capacity, drug release kinetics and transmembrane properties. Moreover, the existing applications of the molecular dynamic simulation technology in the formulation prediction of self-assembled NDDS were also summarized. It is expected that the new strategies will promote the prediction of NDDS formulation and lay a theoretical foundation for an appropriate approach in NDDS studies and a reference for the wider application of molecular dynamics simulation technology in pharmaceutics.
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Antibacterial therapy is a global health issue. The antibiotic resistance is becoming an increasingly serious threat, which caused by misuse and overuse of antibacterial agents combined with the emergence of new resistance mechanism. The resulting infection treatment risk and incidence of the spread of disease, severe cases and deaths are increased in different degrees. With the extensive application of biomaterials and nanotechnology to biomedicine, extensive research has been conducted on antibacterial infection. With the specific physicochemical properties like optical, electric and magnetic and high penetration, inorganic nanomaterials can produce natural antibacterial effect. Nanomedicine can be designed to allow controlled drug release and targeting effect, thus demonstrated better antibacterial efficiency. In this review, the mechanism of antibacterial resistance is described, and the antibacterial infection research on inorganic nanomaterials, as well as nano-drug delivery system including liposomes, nanoparticles, dendrimers and biomimetic nanocarriers are summarized. Nanomaterials and nanotechnology offer promising strategies for the development of new agents that can improve efficacy on antibacterial infections and overcome antibiotic resistance potentially.
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Brain delivery of drugs remains challenging due to the presence of the blood-brain barrier (BBB). With advances in nanotechnology and biotechnology, new possibilities for brain-targeted drug delivery have emerged. Biomimetic nano drug delivery systems with high brain-targeting and BBB-penetrating capabilities, along with good biocompatibility and safety, can enable 'invisible' drug delivery. In this review, five different types of biomimetic strategies are presented and their research progress in central nervous system disorders is reviewed. Finally, the challenges and future prospects for biomimetic nano drug delivery systems in intracerebral drug delivery are summarized.
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Traditional surgical resection, radiotherapy, and chemotherapy still play a dominant role in the treatment of liver cancer; however, their application in liver cancer patients is often limited by the toxic and side effects, unstable efficacy, and unclear targets of chemotherapeutic drugs. Therefore, in order to improve the efficacy of drugs in the treatment of liver cancer, nanomedicine, which has been developed in the biomedical field in recent years, has attracted more and more attention. Nano-drug delivery system has been gradually applied in clinical research for its advantages of low toxicity, wide bioavailability, controllable drug release, and good stability. This article focuses on the latest research advances in nano-drug delivery system in the treatment of liver cancer.
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Objective: Using polydopamine (PDA) as a carrier to construct a Salviae Miltiorrhizae Radix et Rhizoma (SMRR) nano-delivery system (PDA-SMRR), which can load a large number of SMRR water-soluble components and better exert antioxidation and antistress effect. Methods: PDA-SMRR nanoparticles (PDA-SMRR) were prepared, and the prescription process was investigated and optimized by single-factor experiments. The particle size, potential, and morphology of the nanoparticles were examined by a laser particle size analyzer and a transmission electron microscope. The drug loading and cumulative release rate were analyzed by dialysis. The cardiomyocytes of neonatal rats were extracted and cultured. The CCK-8 experiment was used to investigate the biological safety of PDA-SMRR and verify the protective effect of PDA-SMRR on oxidative stress-induced cardiomyocytes. Results: The optimal drug loading process was pH value 3.5, drug loading time was 12 h, drug loading temperature was room temperature, and PDA-SMRR was successfully prepared. The morphology and size of the nanoparticles were regular and uniform. The particle size and Zeta potential were (459.2 ± 4.5) nm, (3.01 ± 0.3) mV; In vitro release experiments indicated that SMRR was released slowly by the delivery system. CCK-8 experiments showed that PDA-SMRR had good biological safety and nanoparticles can reduce damaged cardiomyocytes caused by oxidative stress. Conclusion: PDA-SMRR can be used as a multi-component medicine depot for SMRR, with high drug loading and sustained release effect, which can effectively reduce the damage of oxidative damage on myocardial cells.
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Immune escape is an important mechanism for the development of tumors. Re-activating the anti-tumor immune response is a key measure for the treatment of malignant tumors. Ginsenoside Rg3 (G-Rg3) is a sterol compound isolated from Panax ginseng. It can improve the anti-tumor immune response of human by up-regulating the autoantigenicity and immunogenicity of tumor cells, enhancing the function of immune effector cells and immune active molecules, and regulating the local immune microenvironment. However, the clinical application of G-Rg3 is limited due to its poor water solubility and low bioavailability. Improved drug delivery systems are the key to solving this problem. Therefore, this paper summarizes the research progress of G-Rg3 on tumor immunoregulation and its nano-drug delivery systems, in order to provide reference for the in-depth study and clinical application of G-Rg3.
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@#Anti-angiogenic therapy has a wide range of applications in the treatment of tumor. Nano drug delivery system can contribute to higher efficacy and lower toxicity in anti-angiogenic therapy. This article reviews the application of nano drug delivery system in anti-angiogenic therapy and introduces the strategies to improve its treatment efficiency with varieties of nanoparticles, providing reference for the development of anti-angiogenic therapy.
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Cancer is one of the major diseases that seriously endanger human health. Recurrence and metastasis may still oc-cur after traditional treatment. The basic reason is the presence of cancer stem cells(CSCs)in tumor tissues. CSCs have a high degree of proliferative ability,self-renewal,multi-directional differentiation,highly tumorigenicity and multi-drug resistance,which control the occurrence and development of tumors,chemotherapy tolerance,recurrence and metastasis. Therefore,clearing CSCs is one of effec-tive ways to improve the curative rate of cancer. Nano-carriers have many advantages such as small size,large specific surface area, good biocompatibility and degradation in vivo. They are often used for targeted delivery and sustained release of drugs,which overcome the toxic side effects of traditional chemotherapeutic drugs,avoid surgical damage and kill CSCs. This paper will review the characteris-tics of CSCs and nano drug-loading systems as well as their research progress of nano drug-loading systems in CSCs in recent years.
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@#Tumor occurrence is usually recognized as the interplay between genetic variations within the tumor and the environment. During a long time, great effort has been made in killing cancer cells. However, the role of tumor microenvironment has been largely ignored, which plays an important role in tumor generation, growth, invasion and metastasis. Meanwhile, tumor microenvironment not only facilitates the tumor infiltration, but also promotes the exchange of enzymes and cytokines to aid tumor proliferation, differentiation and self-renewal. Thus, better understanding of tumor microenvironment shows great importance. Recent developments in nanotechnology have brought new approaches to cancer diagnosis and therapy. Nanoparticles were suggested to show enhanced efficacy, while simultaneously reducing side effects and promoting bioavailability, owing to properties such as tumor localization and active cellular uptake. Additionally, nanoparticle surface chemistry has evolved from conventional synthetic polymers to more biologically inspired strategies, including cell membrane and self-recognition peptides, to minimize nonspecific uptake of nanoparticles. In the current review, we highlight the targets in tumor microenvironment and the strategies of nano drug delivery system to target tumor microenvironment for the treatment of cancer. We also highlight design considerations to improve nano drug delivery.
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Multidrug resistance (MDR) seriously affects the clinical efficacy of chemotherapeutic drugs. One of the main mechanisms of MDR is the overexpression of P-glycoprotein (P-gp) in tumor cells that reduces the intracellular drug concentrations and limits the effective use of chemotherapeutic drugs. Accordingly, application of P-gp inhibitors that can reverse tumor MDR is an effective strategy to enhance the anti-tumor effect of chemotherapeutic drugs. In recent years, D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) has been widely applied as the potential P-gp inhibitor for its excellent P-gp inhibition effect as well as good safety. In this paper, we reviewed the P-gp inhibitors, the mechanisms of TPGS in reversing P-gp-mediated MDR and the application of TPGS-based nano-drug delivery system.
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Nano-drug delivery systems (nano-DDS) are the hotspots of new drug delivery systems, which have many advantages, such as sustained and controlled release, targeting delivery. Traditional pharmacokinetics are difficult to predict the efficacy of drugs in vivo sometimes. It is urgently needed to extend the traditional pharmacokinetics studies to the cell/subcellular level and perform cell pharmacokinetic studies. The study on the pharmacokinetics of nano-DDS helps us to elucidate the mechanism of the actions of them in cells and guides us to design and develop nano-DDS more reasonably. This article summarizes the research content and methods on the cellular pharmacokinetics of nano-DDS, in order to provide an important reference for the early stage design of nano-DDS.
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Quercetin has a variety of biological activities and pharmacological effects, but its clinical application is limited due to its low water solubility, low bioavailability and poor chemical stability. In order to overcome the above shortcomings of quercetin and achieve better clinical efficacy, many new drug delivery systems have been studied and developed in recent years, of which nano drug delivery system has become a research hotspot. Nano drug delivery system includes nanoparticles, nanocapsules, nanoliposomes, nanomicelles, nanosuspensions and nanoemulsions, with the advantages of reducing particle size, enlarging surface area, increasing drug permeability, improving intracorporeal circulation and distribution of the drug, enhancing drug targeting and so on. This article reviewed the latest progress at home and abroad about the studies and application of quercetin in nano drug delivery system, such as increasing solubility and dissolution, elevating bioavailability, raising drug stability, delaying drug release, enhancing skin permeability, promoting antioxidant capacity and improving therapeutic effect, in the hope of providing references for further research of quercetin preparations.
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Exosomes are natural nano vesicles secreted by living cells, which play an important role in cellular communication and substance transportation. As a kind of carrier of human endogenous for drug transportation, many advantages of exosomes are in sight, for example, low toxicity, non immunogenicity, good permeability and high-targeting. In recent years, small molecular chemical drugs, nucleic acids and proteins have been successfully delivered by exosomes. This novel carrier is expected to provide strong support for the clinical treatment of myocardial ischemia. The research progress of exosomes as a kind of carrier in the treatment of myocardial ischemia was briefly summarized in this article.
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OBJECTIVE:To establish the mesoporous carbon nano-drug delivery system (MCNs) with chemotherapy drugs loaded and holding photothermal and photodynamic combined effect,and study its anti-multidrug-resistant tumor effect in vitro. METHODS:MCNs was prepared by low-concentration hydrothermal route,and the MCNs surface was carboxylated by the mixed acid ultrasound method to made MCNs-COOH (MCNC). The morphology and surface properties were evaluated. Adriamycinc (ADR)was loaded into MCNC to fabricate ADR/MCNC via adsorption method. Drug loading capacity was calculated by UV,and drug release profile was investigated by dialysis method. ADR-resistant human breast cancer MCF-7/ADR cells were chosen,and cell uptake and positioning of ADR/MCNC were observed by confocal laser microscopy;cytotoxicity of ADR/MCNC was detected by MTT method;and intracellular reactive oxygen species(ROS)level under NIR irradiation was measured by flow cytometry. RE-SULTS:The particle size of prepared MCNs was about 90 nm,with carboxyl in surface. The specific surface area was 541.62 m2/g,pore volume was 0.34 cm3/g,and pore size distribution was 2.5 nm,with significant photothermal effect. The drug loading ca-pacity of ADR/MCNC was 47.4%,showing pH/NIR responsiveness release characteristics. It can promote ADR in cell uptake and nuclear accumulation and induce MCF-7/ADR cell to generate ROS under NIR irradiation,with significant inhibitory effect. CON-CLUSIONS:MCNs is prepared successfully,and ADR/MCNC has an effect on anti-multidrug-resistant tumors.
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Artemisinin and its derivatives have shown the potential application value in anti-tumor fields.But their applications are limited due to poor solubility, short half-life and so on;therefore, many scholars devoted themselves to developing and studying relative pharmaceutical preparations.Nano drug delivery system is a new drug delivery tool.Compared with the traditional dosage forms, such as tablets, suppositories and injections, nano drug delivery system has such advantages as good stability, targeted drug release and combined drug delivery.In this review, nano drug delivery carriers for artemisinin were summarized, including nanoparticles, liposomes, micelles, nanomicroemulsions and so on.The research results and characteristics of artemisinin-containing nano formulas in tumor therapy, as well as the co-delivery system of artemisinin and transferrin, were discussed.
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Stimuli-responsive nano drug delivery systems based on specific structures and physicochemical properties of tumor have been drawing wide attention from researchers, one of which is charge-reversal nano drug delivery system(CRN-DDS). CRN-DDS can effectively combine the merits of positive and negative charges in the drug delivery process in vivo, and it also has the good property of tumor-targeting. Although studies of CRN-DDS application in cancer therapy have already been reported, there is very little relevant Chinese literature, especially review articles. To fill in the blank, the foreign literatures about CRN-DDS were looked up in the last six years, classified CRN-DDSs by their different approaches of surface charge reversal, and summarized the studies on their applications in the cancer therapy. Last but not least, the prospect of CRN-DDS's development and application was preliminarily looked into in this article.
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Central nervous system (CNS) diseases are serious threats to human health. Blood-brain barrier (BBB) plays an important role in protecting the CNS. However, it also impedes the delivery of drugs to CNS and affects the treatment of CNS diseases. Brain targeted nano-drug delivery systems provide the possibility to brain-targeting drug delivery. In this article, we introduce the physiological structure and functions of BBB, and the brain targeting mechanism and the applications of brain-targeting nano-vectors to give a brief overview of the research status of brain targeting nano-drug delivery system.
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Central nervous system(CNS)diseases are serious threats to human health. Blood-brain barrier(BBB)plays an im?portant role in protecting the CNS. However,it also impedes the delivery of drugs to CNS and affects the treatment of CNS diseases. Brain targeted nano-drug delivery systems provide the possibility to brain-targeting drug delivery. In this article,we introduce the phys?iological structure and functions of BBB,and the brain targeting mechanism and the applications of brain-targeting nano-vectors to give a brief overview of the research status of brain targeting nano-drug delivery system.
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RESULTS: The drug carrier was modified with bifunctional-ligands, which could help the drug delivery system penetrate the blood-brain barrier and concentrate on lesions, thus improving the drug efficacy and reducing the side effects.