Functional delivery vehicle of organic nanoparticles in inorganic crystals

This work has developed a functional delivery vehicle of an organic-inorganic hybrid consisted of organic nanoparticles in inorganic crystals, which greatly improves the stability of the bioactive and implements a unique pH-triggered release.     

Mesoporous silica nanoparticles for 19F magnetic resonance imaging,fluorescence imaging,and drug delivery

Multifunctional mesoporous silica nanoparticles (MSNs) are good candidates for multimodal applications in drug delivery, bioimaging, and cell targeting. In particular, controlled release of drugs from MSN pores constitutes one of the superior features of MSNs. In this study, a novel drug delivery carrier based on MSNs, which encapsulated highly sensitive ¹⁹F magnetic resonance imaging (MRI) contrast agents inside MSNs, was developed. The nanoparticles were labeled with fluorescent dyes and functionalized with small molecule-based ligands for active targeting. This drug delivery system facilitated the monitoring of the biodistribution of the drug carrier by dual modal imaging (NIR/¹⁹F MRI). Furthermore, we demonstrated targeted drug delivery and cellular imaging by the conjugation of nanoparticles with folic acid. An anticancer drug (doxorubicin, DOX) was loaded in the pores of folate-functionalized MSNs for intracellular drug delivery. The release rates of DOX from the nanoparticles increased under acidic conditions, and were favorable for controlled drug release to cancer cells. Our results suggested that MSNs may serve as promising ¹⁹F MRI-traceable drug carriers for application in cancer therapy and bio-imaging.     

Self-Assembled Plasmonic Vesicles of SERS-Encoded Amphiphilic Gold Nanoparticles for Cancer Cell Targeting and Traceable Intracellular Drug Delivery

We report the development of bioconjugated plasmonic vesicles assembled from SERS-encoded amphiphilic gold nanoparticles for cancer-targeted drug delivery. This new type of plasmonic assemblies with a hollow cavity can play multifunctional roles as delivery carriers for anticancer drugs and SERS-active plasmonic imaging probes to specifically label targeted cancer cells and monitor intracellular drug delivery. We have shown that the pH-responsive disassembly of the plasmonic vesicle, stimulated by the hydrophobic-to-hydrophilic transition of the hydrophobic brushes in acidic intracellular compartments, allows for triggered intracellular drug release. Because self-assembled plasmonic vesicles exhibit significantly different plasmonic properties and greatly enhanced SERS intensity in comparison with single gold nanoparticles due to strong interparticle plasmonic coupling, disassembly of the vesicles in endocytic compartments leads to dramatic changes in scattering properties and SERS signals, which can serve as independent feedback mechanisms to signal cargo release from the vesicles. The unique structural and optical properties of the plasmonic vesicle have made it a promising platform for targeted combination therapy and theranostic applications by taking advantage of recent advances in gold nanostructure based in vivo bioimaging and photothermal therapy and their loading capacity for both hydrophilic (nucleic acids and proteins) and hydrophobic (small molecules) therapeutic agents.     

聚乳酸纳米粒的改性研究进展

聚乳酸纳米粒具有控制药物释放速度以达到长效缓释、增加药物靶向性、降低毒副作用以及提高疗效等优点,在药物传输中有着广阔的研究和应用前景。但由于聚乳酸的疏水性和分子链基团的单一性,它在靶向制剂和长效制剂的应用方面受到很大制约。本文对可生物降解材料聚乳酸作为载药纳米粒的改性研究状况进行了综述,针对目前制约聚乳酸纳米粒临床应用存在的问题,介绍了亲水性修饰、靶向修饰的最新研究进展。     

A new class of silica cross-linked micellar core-shell nanoparticles

Micellar nanoparticles made of surfactants and polymers have attracted wide attention in the materials and biomedical community for controlled drug delivery, molecular imaging, and sensing; however, their long-term stability remains a topic of intense study. Here we report a new class of robust, ultrafine silica core-shell nanoparticles formed from silica cross-linked, individual block copolymer micelles. Compared with pure polymeric micelles, the main advantage of the new core-shell nanoparticles is that they have significantly improved stability and do not break down during dilution. We also studied the drug loading and release properties of the silica cross-linked micellar particles, and we found that the new core-shell nanoparticles have a slower release rate which allows the entrapped molecules to be slowly released over a much longer period of time under the same experimental conditions. A range of functional groups can be easily incorporated through co-condensation with the silica matrix. The potential to deliver hydrophobic agents into cancer cells has been demonstrated. Because of their unique structures and properties, these novel core-shell nanoparticles could potentially provide a new nanomedicine platform for imaging, detection, and treatment, as well as novel colloidal particles and building blocks for mutlifunctional materials.     

Heterostructured magnetic nanotubes

Heterostructured magnetic tubes with submicrometer dimensions were assembled by the layer-by-layer deposition of polyelectrolytes and nanoparticles in the pores of track-etched polycarbonate membranes. Multilayers composed of poly(allylamine hydrochloride) and poly(styrene sulfonate) assembled at high pH (pH > 9.0) were first assembled into the pores of track-etched polycarbonate membranes, and then multilayers of magnetite (Fe3O4) nanoparticles and PAH were deposited. Transmission electron microscopy (TEM) confirmed the formation of multilayer nanotubes with an inner shell of magnetite nanoparticles. These tubes exhibited superparamagnetic characteristics at room temperature (300 K) as determined by a SQUID magnetometer. The surface of the magnetic nanotubes could be further functionalized by adsorbing poly(ethylene oxide)-b-poly(methacrylic acid) block copolymers. The separation and release behavior of low molecular weight anionic molecules (i.e., ibuprofen, rose bengal, and acid red 8) by/from the multilayer nanotubes were studied because these tubes could potentially be used as separation or targeted delivery vehicles. The magnetic tubes could be successfully used to separate (or remove) a high concentration of dye molecules (i.e., rose bengal) from solution by activating the nanotubes in acidic solution. The release of the anionic molecules in physiologically relevant buffer solution showed that whereas bulky molecules (e.g., rose bengal) release slowly, small molecules (i.e., ibuprofen) release rapidly from the multilayers. The combination of the template method and layer-by-layer deposition of polyelectrolytes and nanoparticles provides a versatile means to create functional nanotubes with heterostructures that can be used for separation as well as targeted delivery.     

Single‐Vehicular Delivery of Antagomir and Small Molecules to Inhibit miR‐122 Function in Hepatocellular Carcinoma Cells by using “Smart” Mesoporous Silica Nanoparticles

MicroRNAs (miRNAs) regulate a variety of biological processes. The liver‐specific, highly abundant miR‐122 is implicated in many human diseases including cancer. Its inhibition has been found to result in a dramatic loss in the ability of Hepatitis C virus (HCV) to infect host cells. Both antisense technology and small molecules have been used to independently inhibit endogenous miR‐122 function, but not in combination. Intracellular stability, efficient delivery, hydrophobicity, and controlled release are some of the current challenges associated with these novel therapeutic methods. Reported herein is the first single‐vehicular system, based on mesoporous silica nanoparticles (MSNs), for simultaneous cellular delivery of miR‐122 antagomir and small molecule inhibitors. The controlled release of both types of inhibitors depends on the expression levels of endogenous miR‐122, thus enabling these drug‐loaded MSNs to achieve combination inhibition of its targeted mRNAs in Huh7 cells.     

Hollow spherical mesoporous phosphosilicate nanoparticles as a delivery vehicle for an antibiotic drug

Mesoporous phosphosilicate nanoparticles of hollow sphere architecture have been prepared hydrothermally for the first time under acidic pH conditions and this material is found to be efficient in encapsulating an antibiotic drug and its controlled release at physiological pH for possible cargo delivery applications.     

Taking Advantage of Hydrophobic Fluorine Interactions for Self‐Assembled Quantum Dots as a Delivery Platform for Enzymes

Self‐assembly of nanoparticles provides unique opportunities as nanoplatforms for controlled delivery. By exploiting the important role of noncovalent hydrophobic interactions in the engineering of stable assemblies, nanoassemblies were formed by the self‐assembly of fluorinated quantum dots in aqueous medium through fluorine–fluorine interactions. These nanoassemblies encapsulated different enzymes (laccase and α‐galactosidase) with encapsulation efficiencies of ≥74 %. Importantly, the encapsulated enzymes maintained their catalytic activity, following Michaelis–Menten kinetics. Under an acidic environment the nanoassemblies were slowly disassembled, thus allowing the release of encapsulated enzymes. The effective release of the assayed enzymes demonstrated the feasibility of this nanoplatform to be used in pH‐mediated enzyme delivery. In addition, the as‐synthesized nanoassemblies, having a diameter of about 50 nm, presented high colloidal stability and fluorescence emission, which make them a promising multifunctional nanoplatform.     

Theranostic hyaluronic acid prodrug micelles with aggregation-induced emission characteristics for targeted drug delivery

Theranostic hyaluronic acid (HA) prodrug micelles with pH-responsive drug release and aggregation-induced emission (AIE) properties were prepared by chemical graft of biomimetic phosphorylcholine (PC), anticancer drug doxorubicin (DOX) and AIE fluorogen tetraphenylene (TPE) to the HA backbone. DOX was conjugated to the HA backbone by a hydrazone bond which can be hydrolyzed under acidic environment and result in pH-triggered smart release of DOX. The TPE units with typical AIE characteristics were applied for real time drug tracking in cancer cells. The HA-based prodrugs could self-assemble into micelles in aqueous solution as confirmed by the dynamic light scattering (DLS) and transmission electron microscopy (TEM). The intracellular distribution of HA prodrug micelles could be clearly observed by fluorescence microscopy based on the strong fluorescence of TPE. Moreover, after treated with the micelles, stronger fluorescence of TPE in CD44 overexpressed MDA-MB-231 cancer cells was observed, compared to the CD44 negative cell line, NIH3T3 cells, suggesting efficient cell uptake of HA prodrug micelles by receptor-mediated endocytosis. The cell viability results indicated that the prodrug micelles could inhibit the proliferation of the cancer cells effectively. Such pH-triggered theranostic drug delivery system with AIE features can provide a new platform for targeted and image-guided cancer therapy.     

Electrosprayed core-shell nanoparticles of PVP and shellac for furnishing biphasic controlled release of ferulic acid

Coaxial electrospraying was explored to organize polymer excipients in a core-shell manner for providing biphasic controlled release of active ingredient. With ferulic acid (FA) as a model drug, and shellac and polyvinylpyrrolidone (PVP) as the core and shell polymeric matrices, core-shell nanoparticles were successfully fabricated. A series of tests were carried out to characterize the prepared core-shell nanoparticles and also the nanoparticles prepared using a single fluid electrospraying of the shell or core fluids alone. The core-shell nanoparticles had an average diameter of 530?±?80 nm with clear core-shell structure. The contained FA was converted to an amorphous state both in the core and the shell parts due to the favorable hydrogen bonding between the components. In vitro dissolution tests demonstrated that the core-shell nanoparticles were able to provide the desired biphasic drug-controlled release profiles. Coaxial electrospraying is a useful tool for the development of novel nanodrug delivery systems from polymers.     

Incorporation of nanogels within calcite single crystals for the storage,protection and controlled release of active compounds

Nanocarriers have tremendous potential for the encapsulation, storage and delivery of active compounds. However, current formulations often employ open structures that achieve efficient loading of active agents, but that suffer undesired leakage and instability of the payloads over time. Here, a straightforward strategy that overcomes these issues is presented, in which protein nanogels are encapsulated within single crystals of calcite (CaCO₃). Demonstrating our approach with bovine serum albumin (BSA) nanogels loaded with (bio)active compounds, including doxorubicin (a chemotherapeutic drug) and lysozyme (an antibacterial enzyme), we show that these nanogels can be occluded within calcite host crystals at levels of up to 45 vol%. Encapsulated within the dense mineral, the active compounds are stable against harsh conditions such as high temperature and pH, and controlled release can be triggered by a simple reduction of the pH. Comparisons with analogous systems – amorphous calcium carbonate, mesoporous vaterite (CaCO₃) polycrystals, and calcite crystals containing polymer vesicles – demonstrate the superior encapsulation performance of the nanogel/calcite system. This opens the door to encapsulating a broad range of existing nanocarrier systems within single crystal hosts for the efficient storage, transport and controlled release of various active guest species.

Nanocarriers have tremendous potential for the encapsulation, storage and delivery of active compounds.     

Biodegradable and antibacterial poly(azomethine‐urethane)‐chitosan hydrogels for potential drug delivery application

In this study, biodegradable and antibacterial poly(azomethine‐urethane) (PAMU)‐ and chitosan (CS)‐based hydrogels have been prepared for controlled drug delivery applications. Structural and morphological characterizations of the hydrogels were performed via Fourier transform‐infrared and scanning electron microscopy analyses. Thermal stability, hydrophilicity, swelling, mechanical, biodegradation, protein absorption properties, and drug delivery application of PAMU‐ and CS‐based hydrogels were also investigated. The swelling performance of the hydrogels was studied in acidic, neutral, and alkaline media. Swelling results showed that the hydrogels have higher swelling capacity in acidic and alkaline media than neutral medium. Biodegradation experiments of the hydrogels were also studied via hydrolytic and enzymatic experiments. The drug release property of the hydrogel was carried out using 5‐fluoro uracil (5‐FU), and 5‐FU release capacity of the hydrogels was found in the range from 40.10% to 58.40% after 3 days.     

Interactions of salicylic acid derivatives with calcite crystals

Investigation of basic interactions between the active pharmaceutical compounds and calcium carbonates is of great importance because of the possibility to use the carbonates as a mineral carrier in drug delivery systems. In this study the mode and extent of interactions of salicylic acid and its amino acid derivates, chosen as pharmaceutically relevant model compounds, with calcite crystals are described. Therefore, the crystal growth kinetics of well defined rhombohedral calcite seed crystals in the systems containing salicylic acid (SA), 5-amino salicylic acid (5-ASA), N-salicyloil-l-aspartic acid (N-Sal-Asp) or N-salicyloil-l-glutamic acid (N-Sal-Glu), were investigated. The precipitation systems were of relatively low initial supersaturation and of apparently neutral pH. The data on the crystal growth rate reductions in the presence of the applied salicylate molecules were analyzed by means of Cabrera & Vermileya's, and Kubota & Mullin's models of interactions of the dissolved additives and crystal surfaces. The crystal growth kinetic experiments were additionally supported with the appropriate electrokinetic, spectroscopic and adsorption measurements. The Langmuir adsorption constants were determined and they were found to be in a good correlation with values obtained from crystal growth kinetic analyses. The results indicated that salicylate molecules preferentially adsorb along the steps on the growing calcite surfaces. The values of average spacing between the adjacent salicylate adsorption active sites and the average distance between the neighboring adsorbed salicylate molecules were also estimated.     

Controlled Release of a Sparingly Water‐Soluble Anticancer Drug through pH‐Responsive Functionalized Gold‐Nanoparticle‐Decorated Liposomes

The binding and detachment of carboxyl‐modified gold nanoparticles from liposomes is used for controlled drug delivery. This study reveals that the binding and detachment of nanoparticles from liposomes depends on the degree of hydration of the liposomes. Liposomes with a lower hydration level undergo stronger electrostatic interactions with negatively charged gold nanoparticles, thus leading to a slower detachment of the carboxyl‐modified gold nanoparticles under gastric conditions. Therefore, under gastric conditions, gold‐nanoparticle‐decorated dipalmitoylphosphatidylcholine (DPPC) liposomes exhibit an at least ten‐times‐slower drug release compared to gold‐nanoparticle‐decorated 1,2‐dimyristoyl‐sn‐glycero‐3‐phosphocholine (DMPC) liposomes, although both liposomes in the bare state fail to pursue controlled release. Our study also reveals that one can modulate the drug‐release rate by simply varying the concentration of nanoparticles. This study highlights a novel strategy for the controlled release of drug molecules from liposomes.     

羟基喜树碱-类水滑石纳米杂化的共组装制备及表征

采用共组装法在水溶液中制备羟基喜树碱(HCPT)-层状双金属氢氧化物(LDH)纳米杂化物.先利用微通道反应器通过共沉淀法制备了Zn₂Al-NO₃ LDH纳米片,然后与羧酸盐型HCPT在水介质中共组装,制备了HCPT插层LDH的纳米杂化物.利用酸处理,可将层间HCPT由非生物活性的羧酸盐型转化为生物活性的内酯型,这对高生物活性HCPT-LDH纳米杂化物的绿色制备具有重要意义.共组装法制备HCPT-LDH纳米杂化物,耗时短、载药量高、分散性好,且利用原料配比可方便地调控载药量. HCPT分子在LDH层间以其长轴倾斜于层板呈双层排列.所制备的HCPT-LDH纳米杂化物具有良好的药物缓释性能,颗粒内部扩散是药物释放过程的控速步骤.药物释放过程可用准二级动力学模型描述.可以用于构筑LDH基药物输送-控释体系.     

P(VPBA-DMAEA) as a pH-sensitive nanovalve for mesoporous silica nanoparticles based controlled release

A pH-sensitive controlled release system was proposed in this work, which consists of mesoporous silica nanoparticles(MSNs) functionalized on the pore outlets with poly(4-vinylphenybronic acid-co-2-(dimethylamino)ethyl acrylate) [P(VPBA-DMAEA)]. Four kinds of P(VPBA-DMAEA)-gated MSNs were synthesized and applied for the p H-sensitive controlled release. The results showed that P(VPBADMAEA) can work as a p H-sensitive nanovalve. The release behavior of the hybrid nanoparticles could be adjusted by changing the mole ratio of VPBA and DMAEA. With the increasing of the mole ratio of VPBA,the leakage of the entrapped molecules in the pores of MSNs could be decreased at neutral and alkaline conditions. By altering the p H of buffer from 4.0 to 8.0, the valve could be switched ‘‘on' and ‘‘off'reversibly. In addition, cells viability results indicated that these P(VPBA-DMAEA)-gated MSNs had good biocompatibility. We believe that these MSNs based p H-sensitive controlled release system will provide a promising nanodevice for sited release of drug delivery.     

Cucurbit[<Emphasis Type="Italic">n</Emphasis>]uril-based host–guest-metal ion chemistry: an emerging branch in cucurbit[<Emphasis Type="Italic">n</Emphasis>]uril chemistry

The unique pumpkin-shape macrocyclic structure with inherent cavities renders cucurbituril (CB) a type of versatile supramolecular container. On account of their good biocompatibility and low toxicity, the applications of CB to encapsulate drug molecules provide promising candidates and the pharmacological activities have been investigated currently. How to control over the uptake and release of the guest at will is significant for practical applications of drug delivery. The noncovalent nature of supramolecular interactions offers variety of options to control the release of guest molecules from CB under external stimuli, including pH, temperature, metal cations, competing guests, light, redox and so on. Moreover, CB containers are capable of assembling into higher ordered supramolecular structures such as polymers, nanoparticles, hydrogels, and colloids, which greatly enrich the scope of CB-type inclusion materials. Those results provide useful principles and guidelines for controlled release from supramolecular containers.     

Integration of Mesoporous Bioactive Glass Nanoparticles and Curcumin into PHBV Microspheres as Biocompatible Composite for Drug Delivery Applications

Bioactive glasses (BGs) are being increasingly considered for biomedical applications. One convenient approach to utilize BGs in tissue engineering and drug delivery involves their combination with organic biomaterials in order to form composites with enhanced biocompatibility and biodegradability. In this work, mesoporous bioactive glass nanoparticles (MBGN) have been merged with polyhydroxyalkanoate microspheres with the purpose to develop drug carriers. The composite carriers (microspheres) were loaded with curcumin as a model drug. The toxicity and delivery rate of composite microspheres were tested in vitro, reaching a curcumin loading efficiency of over 90% and an improving of biocompatibility of different concentrations of MBGN due to its administrations through the composite. The composite microspheres were tested in terms of controlled release, biocompatibility and bioactivity. Our results demonstrate that the composite microspheres can be potentially used in biomedicine due to their dual effects: bioactivity (due to the presence of MBGN) and curcumin release capability.     

A general strategy for one-step fabrication of biocompatible microcapsules with controlled active release

Fabrication of biocompatible core-shell microcapsules in a controllable and scalable manner remains an important but challenging task.Here,we develop a one-step microfluidic approach for the highthroughput production of biocompatible microcapsules,which utilizes single emulsions as templates and controls the precipitation of biocompatible polymer at the water/oil interface.The facile method enables the loading of various oils in the core and the enhancement of polymer shell strength by polyelectrolyte coating.The resulting microcapsules have the advantages of controllability,scalability,biocompatibility,high encapsulation efficiency and high loading capacity.The core-shell microcapsules are ideal delivery vehicles for programmable active release and various controlled release mechanisms are demonstrated,including burst release by vigorous shaking,pH-triggered release for targeted intestinal release and sustained release of perfume over a long period of time.The utility of our technique paves the way for practical applications of core-shell microcapsules.