Photocleavable microcapsules built from photoreactive nanospheres

We show how photo-cross-linking of nanoparticles within the micrometer-sized thin oil shell of water-oil-water emulsion droplets leads to a new species of optically addressable microcontainers. The inner water droplet of these emulsions may contain drugs, dyes, or other water-soluble components, leading to filled containers. The thickness, mechanical stability, and light resistance of the container walls can be controlled in a simple way by the amount and adjustable photoreactivity of the nanoparticles. Importantly, the chemical bonds between the nanoparticles constituting the microcapsule shell can be cleaved photochemically by irradiation with UV light. This optically controlled destruction of our microcontainers opens up a pathway to controlled release of the enclosed components, as will be illustrated by the example of enclosed cyclodextrin molecules.     

Acid‐Labile Acyclic Cucurbit[n]uril Molecular Containers for Controlled Release

Stimuli‐responsive molecular containers are of great importance for controlled drug delivery and other biomedical applications. A new type of acid labile acyclic cucurbit[n ]uril (CB[n ]) molecular containers is presented that can degrade and release the encapsulated cargo at accelerated rates under mildly acidic conditions (pH 5.5–6.5). These containers retain the excellent recognition properties of CB[n ]‐type hosts. A cell culture study demonstrated that the cellular uptake of cargos could be fine‐tuned by complexation with different containers. The release and cell uptake of cargo dye was promoted by acidic pH.     

Sponge-like nanostructured conducting polymers for electrically controlled drug release

An electrically controlled drug release (ECDR) system based on sponge-like nanostructured conducting polymer (CP) polypyrrole (PPy) film was developed. The nanostructured PPy film was composed of template-synthesized nanoporous PPy covered with a thin protective PPy layer. The proposed controlled release system can load drug molecules in the polymer backbones and inside the nanoholes respectively. Electrical stimulation can release drugs from both the polymer backbones and the nanoholes, which significantly improves the drug load and release efficiency. Furthermore, with one drug incorporated in the polymer backbone during electrochemical polymerization, the nanoholes inside the polymer can act as containers to store a different drug, and simultaneous electrically triggered release of different drugs can be realized with this system.     

Modification of activated carbon porosity by pyrolysis under pressure of organic compounds

Co-pyrolysis at relatively low temperature (673 K) and high pressure (10 MPa), using three organic compounds, was used to modify the porosity of the two ACs. The co-pyrolysis is effective for the modification of the porosity of an AC, and the efficiency depends on the organic compound used. The differences found are consequence of the chemical composition of the organic precursor. High pressure pyrolysis produces beneficial results when an organic compound that volatilizes during the preparation is used. Conducting pyrolysis at low temperature permits improved control of the porosity because the rate of gasification can be more tightly controlled.     

Microfluidics assisted synthesis of well-defined spherical polymeric microcapsules and their utilization as potential encapsulants

In this article, the development of a novel technique to fabricate spherical polymeric microcapsules by utilizing microfluidic technology is presented. Atom transfer radical polymerization (ATRP) was employed to synthesize well-defined amphiphilic block copolymers. An organic polymer solution was constrained to adopt the spherical droplets in a continuous water phase at a T-junction microchannel, and the generation of the droplets was studied quantitatively. The flow conditions of two immiscible solutions were adjusted for the successful generation of the polymer droplets. The morphology of the microcapsules was examined. The efficiency of these polymer microcapsules as containers for the storage and controlled release of loaded molecules was evaluated by encapsulating the microcapsules with Congo-red dye and investigating the release performance using temperature controlled UV-VIS spectroscopy.     

Biomimetic Peptide‐Gated Nanoporous Membrane for On‐Demand Molecule Transport

The controllable molecule transport is crucial to realize many highly valuable applications both in vivo and in vitro. Nanoporous membranes, with nanoscopic pores, high porosity, uniform pore dimensions, and controllable surface chemical properties, hold tremendous potential to achieve this function. Herein, we report a nano‐gating system for on‐demand molecule transport based on a peptide‐gated nanoporous membrane. Acting as gatekeeper, the peptides introduced to the nanoporous membrane provide an opportunity to realize on‐demand on–off states via reversible conformational switching of the peptides. This nano‐gating system offers sustained release and can be used as a sophisticated molecule transport platform for localized drug delivery with a feedback function.     

Magnetic-sensitive silica nanospheres for controlled drug release

Recently, magnetic silica-based nanospheres have received great attention and displayed magnificent potential for bioimaging and therapeutic purposes. This study provided a way to accelerate drug release from magnetic-sensitive silica nanospheres by controlled bursting to a therapeutically effective concentration by a high-frequency magnetic field (HFMF). The magnetic-sensitive silica nanospheres were synthesized by an in situ process, with particle sizes about 50 nm and able to release specific amounts of drug in a burst manner via short exposure to a HFMF. The HFMF accelerates the rotation of magnetic nanoparticles deposited in the silica matrix with generated heat energy and subsequently enlarges the nanostructure of the silica matrix to produce porous channels that cause the drug to be released easily. By taking these magnetic-responsive controllable drug release behaviors, the magnetic silica nanospheres can be designed for controlled burst release of therapeutic agents for especially urgent physiological needs.     

An application of transparent mesoporous bulk silica to a titanium dioxide photocatalyst with adsorption and decomposition functions

Mesoporous bulk silica with optical transparency and high porosity can be prepared using a gel-templating method. This unique material has potentially wide-ranging applications as containers of specific molecules, smart deliverers of target molecules, and photonic devices. Among the potential applications, the use of silica as a photocatalyst is explored in this paper; the photocatalyst was prepared by loading titanium dioxide (titania) from the titania precursor solution into the mesoporous structure of silica with a controlled pore size. Even after crystallization, the titania-loaded silica remained highly mesoporous with uniform pore size and optical transparency. The ability of the adsorption and decomposition of acetaldehyde gas was evaluated by measuring the concentration change of the gas with and without the irradiation of ultraviolet rays. As a result, the specific surface area, the amount of titania and the calcination temperature were essential in determining the adsorption ability as well as the decomposition ability.     

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.     

Yoctowell Cavities on Magnetic Silica Nanoparticles for pH Stimuli‐Responsive Controlled Release of Drug Molecules

Drug‐delivery systems that medically transport active molecules to diseased cells, in a controlled manner, have gained much attention in recent years. Yoctowell (1 yL=8 nm³ that is, 10^?24 L volume) cavities on magnetic silica nanoparticles were used for the encapsulation and release of the drug molecule, “mitoxantrone ( MTZ )”, and controlled using naturally occurring stimuli, that is, pH. First, MTZ was encapsulated from a bulk solution under physiological conditions, and then released from the yoctowells, in a controlled manner, by manipulating the pH (7.2–3.0). The sustained release of MTZ , the recovery of active yoctowells after the release process and magnetic properties of nanoparticles provide potential for development of a new generation of drug‐delivery system.     

External-Radiation-Induced Local Hydroxylation Enables Remote Release of Functional Molecules in Tumors

Radiation-induced cleavage for controlled release in vivo is yet to be established. We demonstrate the use of 3,5-dihydroxybenzyl carbamate (DHBC) as a masking group that is selectively and efficiently removed by external radiation in vitro and in vivo. DHBC reacts mainly with hydroxyl radicals produced by radiation to afford hydroxylation at para/ortho positions, followed by 1,4- or 1,6-elimination to rescue the functionality of the client molecule. The reaction is rapid and can liberate functional molecules under physiological conditions. This controlled-release platform is compatible with living systems, as demonstrated by the release of a rhodol fluorophore derivative in cells and tumor xenografts. The combined benefits of the robust caging group, the good release yield, and the independence of penetration depth make DHBC derivatives attractive chemical caging moieties for use in chemical biology and prodrug activation.     

Nanostructures for magnetically triggered release of drugs and biomolecules

Specific targeting and controlled release are crucial factors in the administration of drugs and therapeutic biomolecules. It has been shown that drug delivery systems can significantly benefit of the introduction of superparamagnetic nanoparticles in terms of both targeting and controlled release. Magnetic gradients can be used to target therapeutics to specific regions, while alternating magnetic fields produce frequency-dependent effects at the nanoparticle level. This review reports on the latest developments of multifunctional systems based on magnetic nanoparticles where the release of drugs and/or biomolecules is triggered by the application of an external magnetic field. The potentials of these systems are presented through examples in the fields of surface functionalized magnetic nanoparticles, magnetic polymer nanocomposites and magnetoliposomes. Recent results suggest the importance of integrating multiple functions within a single nanostructured device in order to successfully transport, localize and release drugs and biomolecules.     

DNA-Scaffolded Disulfide Redox Network for Programming Drug-Delivery Kinetics

In response to specific stimuli, dynamic covalent materials enable the generation of new structures by reversibly forming/breaking chemical bonds, thus showing great potential for application in controlled drug release. However, using dynamic covalent chemistry to program drug-delivery kinetics remains challenging. Herein, an in situ polymerization-generated DNA-scaffolded disulfide redox network (DdiSRN) is reported in which nucleic acids are used as a scaffold for dynamic disulfide bonds. The constructed DdiSRN allows selective release of loading cargos inside cancer cells in response to redox stimuli. Moreover, the density of disulfide bonds in network can be tuned by precise control over their position and number on DNA scaffolds. As a result, drug-delivery kinetics can be programmed with a half-life, t_1/2, decreasing from 8.3 to 4.4 h, thus facilitating keeping an adequate drug concentration within the therapeutic window. Both in vitro and in vivo studies confirm that co-delivery of DOX and siRNA in combination with fast drug release inside cells using this DdiSRN enhances the therapeutic effect on multidrug-resistant cancer. This nontrivial therapeutic platform enabling kinetic control provides a good paradigm for precision cancer medicine.     

Sustained release of guaifenesin and ipriflavone from biodegradable coatings

Biodegradable plastics are an interesting class of drug carriers for controlled release, as they can decompose to nontoxic, readily bioresorbable products and are advantageous over conventional biomaterials because they do not require surgical retrieval from the body after completion of treatment. In this work, films of poly(d,l-lactic acid) (d,l-PLA) were deposited by the solvent casting technique, onto the surfaces of stainless steel plates and their biodegradation was studied after immersion in buffer solutions. The release of two model drugs, i.e. guaifenesin and ipriflavone, from the above d,l-PLA systems loaded with these compounds at various concentrations, was also studied.The experimental results showed that for low drug concentrations, the release of guaifenesin is controlled by the biodegradation rate of PLA, whereas for high concentrations the burst effect becomes the dominant release mechanism. The rate of release is faster at low pH values probably due to an acceleration of PLA biodegradation, whereas there are no chemical interactions between drug and polymer, that could essentially influence the release rate of the drug or the biodegradation of the polymer. On the other hand, high guaifenesin concentrations produce increased porosity in the PLA matrix and seem to accelerate its biodegradation and further the drug release rate. Finally, the release of ipriflavone in a mixture of 2-propanol/water is clearly a two stage process and, again, the burst effect seems to control the delivery process at high drug concentration.In conclusion, the present study shows that similar results to those obtained with d,l-PLA tablets loaded with model drugs can be obtained with thin coatings of the same systems. This might be of interest for transfer of the existing knowledge to the design of biomedical implants, treated with coatings of d,l-PLA containing reactive compounds.     

Control of prolonged drug release and compression properties of ibuprofen microspheres with acrylic polymer, eudragit RS, by changing their intraparticle porosity [corrected]

Prolonged-release spherical micro-matrices of ibuprofen with Eudragit RS were prepared using a novel emulsion-solvent diffusion method. Those particles were termed "microspheres" due to their characteristic sponge-like texture and unique dissolution and compression properties unlike conventional microcapsules or microspheres. The internal porosity of microspheres could be easily controlled by changing the concentration of the drug and the polymer in the emulsion droplet (ethanol). With lower concentration of ibuprofen in the ethanol, the resultant microspheres had a higher porosity, about 50%. The drug release rate from the microspheres was interpreted by the Higuchi model of spherical matrices, which depended only on their internal porosity of the microspheres when size distribution and drug content were the same. The tortuosities in the microspheres were found to be almost constant (3-4) irrespective of porosity, suggesting the same internal texture. Microsphere compressibility was much improved over the physical mixture of the drug and polymer owing to the plastic deformation of their sponge-like structure. The more porous microspheres produced stronger tablets [corrected].     

Tunable filtering of chemical signals in a simple nanoscale reaction-diffusion network

We study numerically the filtering capabilities of a nanoscale network of two micrometer-sized containers joined by a nanotube, one of which hosts an enzymatic chemical reaction. Spatiotemporal chemical signals of substrate molecules are injected into the network. The substrate propagates by diffusion and reacts with enzymes distributed in the network prior to the injections. The dimensions of the network are tailored in a way that the transport and enzymatic reaction rates are comparable in size, a situation in which the overall behavior is highly influenced by the geometry and topology of the network. This property is crucial for the functionality of the filter developed in here. It is demonstrated that input signals can be classified in a crude way using a simple setup (a two-container network) and that the classification can be tuned by changing the geometry of the network (the length of the tube connecting the two containers). The filter device we investigate can also be viewed as a primitive chemistry-based computational element in the sense that the information encoded in the signals is processed using chemical reactions. In particular, it is demonstrated that the two-container device may filter out signals based on the average injection frequency.     

Synthesis and Characterization of the Magnetic Molecularly Imprinted Polymer Nanoparticles Using N,N-bis Methacryloyl Ethylenediamine as a New Cross-linking Agent for Controlled Release of Meloxicam

The novel magnetic molecularly imprinted polymers (MMIPs) had been synthesized using N,N-bis methacryloyl ethylenediamine as a cross-linker for the controlled release of meloxicam at a pH of 1.0 (simulated gastric fluid), at a pH of 6.8 (simulated intestinal fluid) and at a pH of 7.4 (simulated biological fluids). The MMIPs were prepared via precipitation polymerization, using Fe₃O₄ as a magnetic component, meloxicam as a template molecule, methacrylic acid (MAA) as a functional monomer and N,N-bis methacryloyl ethylenediamine as a new cross-linker in acetonitrile/dimethyl sulfoxide porogen. Magnetic non-molecularly imprinted polymers (MNIPs) were also prepared with the same synthesis procedure as with MMIPs only without the presence of the template. The obtained MMIPs were characterized using transmission electron microscopy (TEM) and Fourier transform infrared (FT-IR), dynamic light scattering (DLS), X-ray diffraction (XRD), energy-dispersive X-ray spectroscopy (EDX) and vibrating sample magnetometer (VSM). The performance of the MMIPs for the controlled release of meloxicam was assessed, and the results indicated that the magnetic MIPs also had potential applications in drug controlled release.     

Luciferase and luciferin co-immobilized mesoporous silica nanoparticle materials for intracellular biocatalysis

We report a gold nanoparticle (AuNP)-capped mesoporous silica nanoparticle (Au-MSN) platform for intracellular codelivery of an enzyme and a substrate with retention of bioactivity. As a proof-of-concept demonstration, Au-MSNs are shown to release luciferin from the interior pores of MSN upon AuNP uncapping in response to disulfide-reducing antioxidants and codeliver bioactive luciferase from the PEGylated exterior surface of Au-MSN to Hela cells. The effectiveness of luciferase-catalyzed luciferin oxidation and luminescence emission in the presence of intracellular ATP was measured by a luminometer. Overall, the chemical tailorability of the Au-MSN platform to retain enzyme bioactivity, the ability to codeliver enzyme and substrate, and the potential for imaging tumor growth and metastasis afforded by intracellular ATP- and glutathione-dependent bioluminescence make this platform appealing for intracellular controlled catalysis and tumor imaging.     

Self-Organization of Magnetic Nanoparticles and Inclusion of Hydrogen by Borohydride Reduction

 Different structures of the interglobular space or voids between self-organized nanoparticles lead to differences in the measurable magnetic properties of single-domain particle chains of similar composition, grain size, and amorphous structure of the single globules. The volumes and radii of nanoparticles obtained by application of a magnetic field (3 to 15 nm) are larger than those determined without application of a magnetic field during the borohydride reduction process. Two types of hydrogen containing nanotubes with diameters of up to 2 (small-size containers) and 5 nm (large-size containers) are produced using as a driving force the domain wall formation energy between ferromagnetic nanoparticles with quantum size effected dimensions prepared by this reduction method at room temperature and ambient atmosphere. Nanoscale hydrogen containers can be used instead of MeH nanoparticle electrodes as perfect energy charge transfer media of high efficiency (close to 100%) using Li ion electrolytes. No influence on the electrode temperature and no participation of OH⁻ and H₂O in the main charge/discharge transfer reactions were observed.     

Controlled microfluidic reconstitution of functional protein from an anhydrous storage depot

A novel method has been developed for preserving molecules in microfluidic devices that also enables the control of the spatial and temporal concentrations of the reconstituted molecules within the devices. In this method, a storage cavity, embedded in a microchannel, is filled with a carbohydrate matrix containing, for example, a reagent. When the matrix is exposed to flowing liquid, it dissolves, resulting in the controlled reconstitution and release of the reagent from the cavity. The technique was demonstrated using two different model systems; the successful preservation and controlled release of beta-galactosidase was achieved. This method has possible applications for simple point-of-care drug delivery and immunoassays, and could be used to pattern the surfaces of microchannels. More broadly, this preservation and controlled release technique can be applied where the preservation and/or spatial and temporal control of chemical concentrations are desired.