Polymer nanocarriers are used as transport modules in the design of the next generation of drug delivery technology. However, the applicability of nanocarrier‐based technology depends strongly on our ability to precisely control and reproduce their synthesis on a large scale because their properties and performances are strongly dependent on their size and shape. Fundamental studies and practical applications of polymer nanocarriers are hampered by the difficulty of using the current methods to produce monodispersed nanocarriers in large quantities and with high reproducibility. Here, a versatile and scalable approach is reported for the large‐scale synthesis of polymer nanocarriers from water‐in‐oil miniemulsions. This method uses microfluidization to perform a controlled emulsification and is proven to be effective to prepare nanocarriers of different biopolymers (polysaccharides, lignin, proteins) up to 43 g min?1 with reproducible size and distribution. 相似文献
Targeted nanocarriers could reach new levels of drug delivery, bringing new tools for personalized medicine. It is known that cancer cells overexpress folate receptors on the cell surface compared to healthy cells, which could be used to create new nanocarriers with specific targeting moiety. In addition, magnetic nanoparticles can be guided under the influence of an external magnetic field in different areas of the body, allowing their precise localization. The main purpose of this paper was to decorate the surface of magnetic nanoparticles with poly(2-hydroxyethyl methacrylate) (PHEMA) by surface-initiated atomic transfer radical polymerization (SI-ATRP) followed by covalent bonding of folic acid to side groups of the polymer to create a high specificity magnetic nanocarrier with increased internalization capacity in tumor cells. The biocompatibility of the nanocarriers was demonstrated by testing them on the NHDF cell line and folate-dependent internalization capacity was tested on three tumor cell lines: MCF-7, HeLa and HepG2. It has also been shown that a higher concentration of folic acid covalently bound to the polymer leads to a higher internalization in tumor cells compared to healthy cells. Last but not least, magnetic resonance imaging was used to highlight the magnetic properties of the functionalized nanoparticles obtained. 相似文献
Nanoscale metal–organic frameworks (nMOFs) have attracted much attention as emerging porous materials as drug delivery carriers. Appropriate surface modification of them can greatly improve stability and introduce biocompatibility and cancer targeting functionality into drug delivery systems. Herein, we prepared nano-sized MIL-101(Fe)-N3 and loaded anticancer drug doxorubicin (DOX) into it. The synthetic polymer layer Alkyne-PLA-PEG was then attached to the F3 peptide (labeled as Alkyne-PLA-PEG-F3), and the surface of DOX/MIL-101(Fe)-N3 was covalently modified with it to obtain DOX/MIL-101-PLA-PEG-F3. Nano-sized MIL-101(Fe)-N3 has high drug loading capacity and the modification of MIL-101(Fe)-N3 by polymer Alkyne-PLA-PEG not only improved the dispersion, but also avoided the sudden release of the drugs and increased the biocompatibility of nanocarriers. The F3 peptide introduced into the nanocarriers also enabled it to specifically target tumor tissues and achieved active targeted drug delivery. As a nucleolin-mediated endocytosis drug delivery system, DOX/MIL-101-PLA-PEG-F3 can not only deliver anticancer drugs to tumors accurately, but also participate in Fenton-like reaction to generate hydroxyl radicals (•OH) for chemodynamic therapy (CDT), thus enabling combination therapy. It holds great promise as drug candidates to reduce systemic toxicity and improve the efficacy of cancer treatment. 相似文献
Nanoparticles with oligonucleotides bound to the outside or incorporated into the matrix can be used for gene editing or to modulate gene expression in the CNS. These nanocarriers are usually optimised for transfection of neurons or glia. They can also facilitate transcytosis across the brain endothelium to circumvent the blood-brain barrier. This review examines the different formulations of nanocarriers and their oligonucleotide cargoes, in relation to their ability to enter the brain and modulate gene expression or disease. The size of the nanocarrier is critical in determining the rate of clearance from the plasma as well as the intracellular routes of endothelial transcytosis. The surface charge is important in determining how it interacts with the endothelium and the target cell. The structure of the oligonucleotide affects its stability and rate of degradation, while the chemical formulation of the nanocarrier primarily controls the location and rate of cargo release. Due to the major anatomical differences between humans and animal models of disease, successful gene therapy with oligonucleotides in humans has required intrathecal injection. In animal models, some progress has been made with intraventricular or intravenous injection of oligonucleotides on nanocarriers. However, getting significant amounts of nanocarriers across the blood-brain barrier in humans will likely require targeting endothelial solute carriers or vesicular transport systems. 相似文献
Iranian Polymer Journal - Smart temperature- and pH-responsive nanocarriers could be considered as potent vehicle in drug delivery systems. By this means, a thermo-responsive polymeric nanocarrier... 相似文献
In the present work, chitin based derivatives carboxymethylchitin, CMC were synthesised for nanocarriers (NCs). Cu and Fu loaded NCs had also been prepared and characterized by various physiochemical & biological techniques. Here, drug release profiles and drug kinetics were also studied. In vitro cytotoxicity test (Cell Viability-A549 cells) result found most effected. CMCNC also fitted best in Higuchi model which proved that this prepared nanocarriers followed the mechanism of diffusion rather than dissolution and degradation. The overall analysis leads to the conclusion that CMCNC found to be a suitable nanocarrier for targeted drug delivery. 相似文献
The aim of study was to develop a novel drug nanocarrier via facile coating of a folate-conjugated dual-responsive copolymer with carboxylic functional groups on the surface of magnetic nanoparticles for the efficient loading and cell-specific targeting of a positively charged anticancer agent. The nanocarrier exhibited many favorable capabilities such as narrow distributed nano-ranged size (~30 nm), high drug loading capacity (~65%), and stimuli-responsive drug release. The results of various cell cytotoxicity studies such as MTT assay, DAPI staining, and flow cytometry concluded that the developed smart nanocarrier paves a way for efficient cancer therapy by the multiple targeting strategies. 相似文献
The emergence and development of nanomedicine have alleviated problems existing in traditional chemotherapy drugs, such as short lifetime, concomitant side effects, and weak tumor-targeting capability. Nevertheless, the further applications of drug-loaded nanocarriers are still limited by their premature leakage, weak targeting capability, and insufficient intracellular release. In past decades, various nanocarriers, including gold nanoparticles, porous silica nanoparticles, carbon-based nanoparticles, micelles, liposomes, and polymer–drug conjugates, have been intensively investigated for tumor therapy. Among these, polymer-based nanocarriers have attracted more attention due to their biocompatibilities and capability of being modified for stimuli-responsive drug release. In this review, three popular strategies to design and synthesize polymer-based stimuli-responsive nanocarriers are discussed. The discussion goes from stimuli-responsive polymers with responsive backbones or modified by responsive functional groups for drug encapsulation and release to polymer–drug conjugates with responsive covalent linkages. In particular, due to the facile synthetic processes and mild reaction conditions for crosslinked structures, the latest progress in responsive crosslinked structures is emphasized. Finally, future perspectives for these nanomaterials are given, which are expected to provide inspiration for researchers to design more effective and safer tumor-killing nanomedicines. 相似文献
Cancer is one of the most important health problems of our population, and one of the common anticancer treatments is chemotherapy. The disadvantages of chemotherapy are related to the drug’s toxic effects, which act on cancer cells and the healthy part of the body. The solution of the problem is drug encapsulation and drug targeting. The present study aimed to develop a novel method of preparing multifunctional 5-Fluorouracil (5-FU) nanocarriers and their in vitro characterization. 5-FU polyaminoacid-based core@shell nanocarriers were formed by encapsulation drug-loaded nanocores with polyaminoacids multilayer shell via layer-by-layer method. The size of prepared nanocarriers ranged between 80–200 nm. Biocompatibility of our nanocarriers as well as activity of the encapsulated drug were confirmed by MTT tests. Moreover, the ability to the real-time observation of developed nanocarriers and drug accumulation inside the target was confirmed by fluorine magnetic resonance imaging (19F-MRI). 相似文献
Considering the recent discoveries on the potential of Clays for turning into an agent of nanotechnology and drug delivery systems, we focused on their different properties as practical nanocarriers for loading/bonding of various drugs. This study introduced a different type of clay as a nanocarrier and attempted to explain its high drug loading capacity, as well as provided data on the superior remedy efficacy of the experimented system. Furthermore, nano-clays displayed a miraculous potential in Nano-Vaccine technology that could be applied for preventing tumor growth and various infectious diseases such as COVID-19, Influenza, pathogenic Escherichia coli (E. coli), and Leptospira. 相似文献
Nanotechnology has brought a variety of new possibilities into biological discovery and clinical practice. In particular, nano-scaled carriers have revolutionalized drug delivery, allowing for therapeutic agents to be selectively targeted on an organ, tissue and cell specific level, also minimizing exposure of healthy tissue to drugs. In this review we discuss and analyze three issues, which are considered to be at the core of nano-scaled drug delivery systems, namely functionalization of nanocarriers, delivery to target organs and in vivo imaging. The latest developments on highly specific conjugation strategies that are used to attach biomolecules to the surface of nanoparticles (NP) are first reviewed. Besides drug carrying capabilities, the functionalization of nanocarriers also facilitate their transport to primary target organs. We highlight the leading advantage of nanocarriers, i.e. their ability to cross the blood-brain barrier (BBB), a tightly packed layer of endothelial cells surrounding the brain that prevents high-molecular weight molecules from entering the brain. The BBB has several transport molecules such as growth factors, insulin and transferrin that can potentially increase the efficiency and kinetics of brain-targeting nanocarriers. Potential treatments for common neurological disorders, such as stroke, tumours and Alzheimer's, are therefore a much sought-after application of nanomedicine. Likewise any other drug delivery system, a number of parameters need to be registered once functionalized NPs are administered, for instance their efficiency in organ-selective targeting, bioaccumulation and excretion. Finally, direct in vivo imaging of nanomaterials is an exciting recent field that can provide real-time tracking of those nanocarriers. We review a range of systems suitable for in vivo imaging and monitoring of drug delivery, with an emphasis on most recently introduced molecular imaging modalities based on optical and hybrid contrast, such as fluorescent protein tomography and multispectral optoacoustic tomography. Overall, great potential is foreseen for nanocarriers in medical diagnostics, therapeutics and molecular targeting. A proposed roadmap for ongoing and future research directions is therefore discussed in detail with emphasis on the development of novel approaches for functionalization, targeting and imaging of nano-based drug delivery systems, a cutting-edge technology poised to change the ways medicine is administered. 相似文献
Amphiphilic block copolymers (ABCs) assemble into a spherical nanoscopic supramolecular core/shell nanostructure termed a polymeric micelle that has been widely researched as an injectable nanocarrier for poorly water-soluble anticancer agents. The aim of this review article is to update progress in the field of drug delivery towards clinical trials, highlighting advances in polymeric micelles used for drug solubilization, reduced off-target toxicity and tumor targeting by the enhanced permeability and retention (EPR) effect. Polymeric micelles vary in stability in blood and drug release rate, and accordingly play different but key roles in drug delivery. For intravenous (IV) infusion, polymeric micelles that disassemble in blood and rapidly release poorly water-soluble anticancer agent such as paclitaxel have been used for drug solubilization, safety and the distinct possibility of toxicity reduction relative to existing solubilizing agents, e.g., Cremophor EL. Stable polymeric micelles are long-circulating in blood and reduce distribution to non-target tissue, lowering off-target toxicity. Further, they participate in the EPR effect in murine tumor models. In summary, polymeric micelles act as injectable nanocarriers for poorly water-soluble anticancer agents, achieving reduced toxicity and targeting tumors by the EPR effect.
Taxanes have been recognized as a family of very efficient anticancer drugs, but the formulation in use for the two main taxanes-Taxol for paclitaxel and Taxotere for docetaxel-have shown dramatic side effects. Whereas several new formulations for paclitaxel have recently appeared, such as Abraxane and others currently in various phases of clinical trials, there is no new formulation in clinical trials for the other main taxane, docetaxel, except BIND-014, a polymeric nanoparticle, which recently entered phase I clinical testing. Therefore, we review herein the state of the art and recent abundance in published results of academic approaches toward nanotechnology-based drug-delivery systems containing nanocarriers and targeting agents for docetaxel formulations. These efforts will certainly enrich the spectrum of docetaxel treatments in the near future. Taxotere's systemic toxicity, low water solubility, and other side effects are significant problems that must be overcome. To avoid the limitations of docetaxel in clinical use, researchers have developed efficient drug-delivery assemblies that consist of a nanocarrier, a targeting agent, and the drug. A wide variety of such engineered nanosystems have been shown to transport and eventually vectorize docetaxel more efficiently than Taxotere in vitro, in vivo, and in pre-clinical administration. Recent progress in drug vectorization has involved a combined therapy and diagnostic ("theranostic") approach in a single drug-delivery vector and could significantly improve the efficiency of such an anticancer drug as well as other drug types. 相似文献
Multifunctional nanocarriers are gaining increasing research interest as polymeric platforms for targeted drug delivery in cancer therapy and diagnosis. In this work, preparation and characterization of surfactant-free polyester nanoparticles (NPs) from a bio-based poly(butylene sebacate-co-butylene dilinoleate)s, poly(butylene sebacate) (PBSE)/poly(butylene dilinoleate) (PBDL), using nanoprecipitation, is reported. The polymeric nanoparticles (sizes narrowly distributed in a range less than 100?nm) were loaded with curcumin (CURC) with an encapsulation efficiency of 98% and drug loading (DL) content of 5–10% wtdrug/wtpolymer. The CURC-loaded nanoparticles were efficiently coated with a novel poly(sulfobetaine)-type zwitterionic polymer synthesized by nitroxide-mediated polymerization and postpolymerization functionalization step. Free and CURC formulated into noncoated and poly(sulfobetaine)-type zwitterionic polymer-coated nanoparticles were further investigated for cytotoxicity and antioxidant activity in a panel of human cell lines and rat liver microsomes, respectively. Formulated into coated NPs, CURC has superior cytotoxic and antioxidant activity versus the free drug and CURC incorporated in noncoated NPs. In addition, cell viability experiments of nonloaded nanoparticles, both coated and noncoated, demonstrated that developed nanoparticles are nontoxic, making them potentially suitable candidates for systemic passive targeting in cancer therapy, namely for treatment of solid tumors exhibiting high tumor accumulation of NPs due to enhanced permeability and retention effect. Polyzwitterion-coated nanoparticles exhibited slower drug release compared with the noncoated ones (half as much after 24?h) presumably due to the presence of the polymer shell around nanoparticles associated with a wider diffusion layer around the particles. 相似文献
A smart mesoporous silica nanocarrier with intracellular controlled release is fabricated, with folic acid as dual-functional targeting and capping agent. The folate not only improves the efficiency of the nanocarrier internalized by the cancer cells, but also blocks the pores of the mesoporous silica to eliminate premature leakage of the drug. With disulfide bonds as linkers to attach the dual-functional folate within the surface of mesoporous silica, the controlled release can be triggered in the presence of reductant dithiothreitol (DTT) or glutathione (GSH). The cellular internalization via folate-receptor-mediated endocytosis and the intracellular controlled release of highly toxic anticancer drug DOX were demonstrated with an in vitro HeLa cell culture, indicating an efficient cancer-targeted drug delivery. 相似文献