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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.
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@#Tumor immunotherapy is a therapeutic modality that uses immunological principles and methods to activate and enhance the body''s immune system to generate immune response for the removal of tumour cells. Many new immunotherapeutic agents have demonstrated effective anti-tumour capabilities, yet their clinical use is challenging due to the complex mechanisms of tumour immune escape. Meanwhile, these drugs would accumulate in different tissues and organs in the human body and be unable to achieve precise and specific targeting therapeutic effects, resulting in serious immune-related adverse effects, which greatly hinders the clinical potential of immunotherapy.Nanodrug delivery systems can deliver immunotherapeutic drugs to target tissues or specific immune cells precisely, thereby enhancing immune effects and reducing side effects.This paper reviews the research progress of nanodrug delivery systems in tumour immunotherapy in recent years based on the regulatory mechanism of the anti-tumour immune response, with a prospect of the challenges and development in this field.
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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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This study screened excellent carriers for co-loading tanshinone Ⅱ_A(TSA) and astragaloside Ⅳ(As) to construct antitumor nano-drug delivery systems for TSA and As. TSA-As microemulsions(TSA-As-MEs) were prepared by water titration. TSA-As metal-organic framework(MOF) nano-delivery system was prepared by loading TSA and As in MOF by the hydrothermal method. Dynamic light scattering(DLS), transmission electron microscopy(TEM), and scanning electron microscopy(SEM) were used to characterize the physicochemical properties of the two preparations. Drug loading was determined by HPLC and the effects of the two preparations on the proliferation of vascular endothelial cells, T lymphocytes, and hepatocellular carcinoma cells were detected by the CCK-8 method. The results showed that the particle size, Zeta potential, and drug loading of TSA-As-MEs were(47.69±0.71) nm,(-14.70±0.49) mV, and(0.22±0.01)%, while those of TSA-As-MOF were(258.3±25.2) nm,(-42.30 ± 1.27) mV, and 15.35%±0.01%. TSA-As-MOF was superior to TSA-As-MEs in drug loading, which could inhibit the proliferation of bEnd.3 cells at a lower concentration and improve the proliferation ability of CTLL-2 cells significantly. Therefore, MOF was preferred as an excellent carrier for TSA and As co-loading.
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Mice , Animals , Endothelial Cells , Abietanes , Cell LineABSTRACT
Neurodegenerative diseases are progressive conditions that affect the neurons of the central nervous system (CNS) and result in their damage and death. Neurodevelopmental disorders include intellectual disability, autism spectrum disorder, and attention-deficit/hyperactivity disorder and stem from the disruption of essential neurodevelopmental processes. The treatment of neurodegenerative and neurodevelopmental conditions, together affecting ∼120 million people worldwide, is challenged by the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier that prevent the crossing of drugs from the systemic circulation into the CNS. The nose-to-brain pathway that bypasses the BBB and increases the brain bioavailability of intranasally administered drugs is promising to improve the treatment of CNS conditions. This pathway is more efficient for nanoparticles than for solutions, hence, the research on intranasal nano-drug delivery systems has grown exponentially over the last decade. Polymeric nanoparticles have become key players in the field owing to the high design and synthetic flexibility. This review describes the challenges faced for the treatment of neurodegenerative and neurodevelopmental conditions, the molecular and cellular features of the nasal mucosa and the contribution of intranasal nano-drug delivery to overcome them. Then, a comprehensive overview of polymeric nanocarriers investigated to increase drug bioavailability in the brain is introduced.
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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.
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Animals , Drugs, Chinese Herbal/chemistry , Plants, Medicinal , Antioxidants , Anti-Inflammatory Agents , Drug CarriersABSTRACT
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.
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Nanomedicine , Nucleosides/chemistry , Nucleotides , Nanoparticles/chemistry , Drug Delivery Systems , Drug CarriersABSTRACT
Objective To find out whether curcumin can be effective in the treatment of traumatic brain injury (TBI). Methods A comprehensive and systematic literature search in the PubMed electronic database was performed. Descriptive statistics were used to evaluate the data obtained. The results were presented as frequency and percentage (%) or amount. Results Two clinical trials investigated curcumin for the treatment of TBI. One study tested curcumin in living mammalian subjects using an amyloLipid nanovesicle. In three studies, curcumin was investigated together with the drug delivery system for the treatment of TBI. Conclusion Drug delivery systems prepared with nanomaterials may have a potential therapeutic effect in treating TBI by increasing neuroprotection because they can penetrate the central nervous system more rapidly.
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Lipid nanoemulsions are promising nanodrug delivery carriers that can improve the efficacy and safety of paclitaxel(PTX).However,no intravenous lipid emulsion of PTX has been approved for clinical treatment,and systemic safety profiles have not yet been reported.Here we outline the development of a PTX-loaded tumor-targeting intravenous lipid emulsion(PTX Emul)and describe its characteristics,colloidal stability,and systemic safety profiles in terms of acute toxicity,long-term toxicity,and tox-icokinetics.We also compare PTX Emul with conventional PTX injection.Results showed that PTX Emul exhibited an ideal average particle size(approximately 160 nm)with narrow size distribution and robust colloidal stability under different conditions.Hypersensitivity reaction and hemolysis tests revealed that PTX Emul did not induce hypersensitivity reactions and had no hemolytic potential.In addition,where the alleviated systemic toxicity of PTX Emul may be attributed to the altered toxicokinetic characteristics in beagle dogs,including the decreased AUC and increased plasma clearance and volume of distribution,PTX Emul alleviated acute and long-term toxicity as evidenced by the enhanced the median lethal dose and approximate lethal dose,moderate body weight change,decreased bone marrow suppression and organ toxicity compared with those under PTX injection at the same dose.A fundamental understanding of the systemic safety profiles,high tumor-targeting efficiency,and superior antitumor activity in vivo of PTX Emul can provide powerful evidence of its therapeutic potential as a future treatment for breast cancer.
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Due to the special physiological and pathological characteristics of gliomas, most therapeutic drugs are prevented from entering the brain. To improve the poor prognosis of existing therapies, researchers have been continuously developing non-invasive methods to overcome barriers to gliomas therapy. Although these strategies can be used clinically to overcome the blood‒brain barrier (BBB), the accurate delivery of drugs to the glioma lesions cannot be ensured. Nano-drug delivery systems (NDDS) have been widely used for precise drug delivery. In recent years, researchers have gathered their wisdom to overcome barriers, so many well-designed NDDS have performed prominently in preclinical studies. These meticulous designs mainly include cascade passing through BBB and targeting to glioma lesions, drug release in response to the glioma microenvironment, biomimetic delivery systems based on endogenous cells/extracellular vesicles/protein, and carriers created according to the active ingredients of traditional Chinese medicines. We reviewed these well-designed NDDS in detail. Furthermore, we discussed the current ongoing and completed clinical trials of NDDS for gliomas therapy, and analyzed the challenges and trends faced by clinical translation of these well-designed NDDS.
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Objective:To investigate the therapeutic efficacy of the combination therapy with CD47-based nanoparticles and anti-PD-L1 monoclonal antibody (αPD-L1) for preventing tumor recurrence and metastasis in vivo.Methods:BALB/c mice were used to construct 4T1 tumor-bearing mouse models. The mouse model was treated with the combination therapy to analyze the effects on local tumor recurrence, tumor growth volume, survival time and lung metastasis in the 4T1 mammary tumor-bearing mouse model.Results:The combination therapy could effectively inhibit local tumor recurrence and prolong the survival time of tumor-bearing mice ( P<0.001). Compared with the αPD-L1 group, the combination therapy can increase the expression of cytokines tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) in mouse serum (all P<0.05) and effector memory T cells in mouse spleen ( P<0.001). In addition, the results on the 4T1-Luc mammary tumor-bearing mouse lung metastasis model showed that the combination therapy could effectively inhibit tumor lung metastasis. Conclusions:The results strongly suggested that combination therapy with CD47-based nanoparticles and αPD-L1 can effectively elicit the memory immune response, and prevent tumor recurrence and lung metastasis.
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A commercial albumin-bound paclitaxel nano-formulation has been considered a gold standard against breast cancer. However, its application still restricted unfavorable pharmacokinetics and the immunogenicity of exogenous albumin carrier. Herein, we report an albumin-bound tumor redox-responsive paclitaxel prodrugs nano-delivery strategy. Using diverse linkages (thioether bond and disulfide bond), paclitaxel (PTX) was conjugated with an albumin-binding maleimide (MAL) functional group. These pure PTX prodrugs could self-assemble to form uniform and spherical nanoparticles (NPs) in aqueous solution without any excipients. By immediately binding to blood circulating albumin after intravenous administration, NPs are rapidly disintegrated into small prodrug/albumin nanoaggregates
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As an extremely important organelle in eukaryotic cells, endoplasmic reticulum (ER) plays a key role in the synthesis and processing of biomacromolecules, material transport, ion homeostasis maintenance, signal transduction, exchange of materials and signals between organelles. Many important human diseases, such as cancers, autoimmune diseases, pathogenic infections, neurodegenerative diseases and diabetes, are closely related to ER dysfunction. With the development of nanotechnology, the exploration and application of ER-targeted nanodrugs gradually become a research hotspot in the field of nanomedicine, bioengineering, material chemistry and other fields. In this paper, the relationship between ER dysfunction and disease occurrence, the principle of designing ER-targeted nanodrugs and their biomedical application are reviewed. ER-targeted nanodrugs are designed based on nanodrug carriers or self-assembly of bioactive molecules. These nanodrugs could target the ER in an active or passive manner and function by disrupting or maintaining the ER functions. The ER-targeting nanodrugs have a wide application prospect in cancer therapy, immune regulation, nervous system repairment, and so on.
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Humans , Endoplasmic Reticulum , Endoplasmic Reticulum Stress , Homeostasis , Neoplasms/drug therapy , Signal TransductionABSTRACT
Objective:To evaluate the radiosensitivity enhancement effect of FePd@CNTs nanocomposites on human breast cancer MCF-7 cells.Methods:FePd@CNTs nanocomposites were synthesized by chemical reduction method. Transmission electron microscope and energy dispersive spectrometer were utilized to characterize the surface morphology and chemical composition of FePd@CNTs nanocomposites. The compatibility of FePd@CNTs nanocomposites with human normal breast epithelial MCF-10A cells was determined by CCK-8 assay. The radiosensitivity enhancement effect of FePd@CNTs nanocomposites on MCF-7 cells was assessed by CCK-8 assay, flow cytometry and clony formation assay.Results:FePd nanospheres were successfully modified on the surface of CNTs by chemical reduction method. FePd@CNTs nanocomposites showed a low toxicity to MCF-10A cells (IC 50=738.3 μg/m), and effectively enhanced the effect of X-ray radiation on MCF-7 cells (sensibilization ratio=1.22). Conclusion:FePd@CNTs nanocomposites exhibit a promising potential for treating breast cancer and enhancing radiosensitivity effect.
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Low temperature plasma(LTP)technology has shown an outstanding application value in the pharma-ceutical filed in recent ten years.This paper reviews the research advances in LTP,including its effects on enhancing or inhibiting drug activity,its combined use with drugs to treat cancers,its effects on the improvement of drug delivery system,its use in preparation of new inactivated virus vaccines,its use with mass spectrometry for rapid detection of drug quality,and the anti-tumor and sterilization effects of plasma-activated liquids.The paper also analyzes the challenges of LTP in the pharmaceutical filed,hoping to promote related research.
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Nanotechnology has emerged as an ideal approach for achieving the efficient chemo agent delivery. However, the potential toxicity and unclear internal metabolism of most nano-carriers was still a major obstacle for the clinical application. Herein, a novel "core‒shell" co-assembly carrier-free nanosystem was constructed based on natural sources of ursolic acid (UA) and polyphenol (EGCG) with the EpCAM-aptamer modification for hepatocellular carcinoma (HCC) synergistic treatment. As the nature products derived from food-plant, UA and EGCG had good anticancer activities and low toxicity. With the simple and "green" method, the nanodrugs had the advantages of good stability, pH-responsive and strong penetration of tumor tissues, which was expected to increase tumor cellular uptake, long circulation and effectively avoid the potential defects of traditional carriers. The nanocomplex exhibited the low cytotoxicity in the normal cells
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Background: Anu Tailam, an Ayurvedic medicated oil where ‘anu’ meant for atom and ‘tailam’ meant foroil and virtually meant for ‘oil of subtle or atomic size particles’. Since the major active ingredients in thisformulation are incorporated from the polyherbal decoction, it is expected to contain predominantlywater soluble ingredients.Objectives: It is hypothesized that these polar active botanical ingredients are present in the formulationshould be either suspended in the form of submicron particles or entrapped in the submicron vesicularstructures since the formulation did not show any precipitation or phase separation instead showed amonophasic oily liquid with very little moisture.Materials and Methods: In the present investigation, the micro architecture of the anu tailam is studiedvia column chromatography and high performance thin layer chromatography to prove the contents arepolar hydrophilic compounds followed by optical microscopy, photon correlation Spectroscopy (PCS) andenvironmental scanning electron microscope (ESEM) to study the particle/vesicle size of the formulation.Results: In this study, it was proved that the formulation contained only polar ingredients and can beextracted in polar solvents like methanol and ethanol. It was also found that the formulation taken forstudy contained nano particles of the active botanical ingredients embedded in a network of vesicularstructures of the lipid base.Conclusion: The selected Ayurvedic formulation ‘anutailam’ found to contain novel nano drug deliverysystem to deliver water soluble ingredients across barriers.
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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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The epithelial-to-mesenchymal transition (EMT), a process during which cells undergo transition from a polarized epithelial phenotype to a non-polarized mesenchymal phenotype, executed by transcription factors of Twist, Snail and Zeb families. EMT plays an important role in multiple stages of cancer progression such as initiation, tumor growth, and metastasis. Some active ingredients from Chinese materia medica can inhibit EMT by regulating transcription factors and signaling pathways by multiple targets. However, their therapeutic effect was hindered due to various limitation such as solubility, stability, tissue specificity and safety. Therefore, in order to improve the druggability of active ingredients from Chinese materia medica, enhance the therapeutic effect in inhibiting tumor metastasis mediated by EMT and reduce the toxic and side effects, a variety of nano-drug delivery systems have been developed in recent years. Here, we made a review about these drug delivery systems modulating EMT and their research progress in inhibiting tumor metastasis.