Modeling of Drug Release from a Novel Temperature-Responsive Phase-Transient Drug Delivery System in Cylindrical Coordinates

In this study, a novel phase-transient multilayer drug delivery system responsive to a unique stimulus, i.e., temperature, was introduced in cylindrical coordinates. The system is composed of three individual sections, including the drug core, phase-transient intermediate layer, and protecting polymeric coverage. The phase-transient layer gives smartness to the system and creates an “On-Off” release profile with increasing or decreasing the environmental temperature around the melting point of the layer. The “On-Off” response of the system was mathematically modeled by analyzing the heat and mass transfer equations in the pseudo-steady state and the effects of various parameters on the performance of the system were investigated. The modeling results showed the intensity of the effects of different kinds of factors, including the geometrical characteristics of the system (e.g., the radius of the drug core and the thicknesses of the intermediate and polymeric layers), the physical properties of the matrix materials (e.g., the thermal conductivities and diffusion coefficients of the intermediate and polymeric layers), and the operation conditions, on the response time lag and release kinetics of the presented system. The obtained results in this study predict methods to prepare multilayer temperature-responsive drug delivery systems with desired and optimized responses (e.g., with a short lag time) for practical biomedical applications.     

Effect of the Semiconductor Quantum Dot Shell Structure on Fluorescence Quenching by Acridine Ligand

The main line of research in cancer treatment is the development of methods for early diagnosis and targeted drug delivery to cancer cells. Fluorescent semiconductor core/shell nanocrystals of quantum dots (e.g., CdSe/ZnS) conjugated with an anticancer drug, e.g., an acridine derivative, allow real-time tracking and control of the process of the drug delivery to tumors. However, linking of acridine derivatives to a quantum dot can be accompanied by quantum dot fluorescence quenching caused by electron transfer from the quantum dot to the organic molecule. In this work, it has been shown that the structure of the shell of the quantum dot plays the decisive role in the process of photoinduced charge transfer from the quantum dot to the acridine ligand, which is responsible for fluorescence quenching. It has been shown that multicomponent ZnS/CdS/ZnS shells of CdSe cores of quantum dots, which have a relatively small thickness, make it possible to significantly suppress a decrease in the quantum yield of fluorescence of quantum dots as compared to both the classical ZnS thin shell and superthick shells of the same composition. Thus, core/multicomponent shell CdSe/ZnS/CdS/ZnS quantum dots can be used as optimal fluorescent probes for the development of systems for diagnosis and treatment of cancer with the use of anticancer compounds based on acridine derivatives.     

A Functionalized Hollow Mesoporous Silica Nanoparticles‐Based Controlled Dual‐Drug Delivery System for Improved Tumor Cell Cytotoxicity

Multifunctional nanoparticles for selectively targeting tumor cells and effectively delivering multiple drugs are urgently needed in cancer therapy. Here, a dual‐drug delivery system is prepared, based on functionalized hollow mesoporous silica nanoparticles (HMSNs). Doxorubicin (DOX) hydrochloride is loaded into the hollow core, and dichloro(1,2‐diaminocyclohexane)platinum (II) (DACHPt) is stored in the pores of the shell by the coordination interaction with the carboxyl groups modified on the pore walls, which also serves as barriers to control the DOX release. Detailed studies in vitro indicate that the DACHPt release is triggered by Cl^? through the cleavage of the coordination interaction, and the DOX release depends on the release rate of DACHPt and the environmental pH value. The surface of the mechanized nanoparticles is also modified by transferrin (Tf) to achieve the tumor specificity. Compared with individual drug delivery systems, the dual‐drug delivery system shows synergistic efficacy on the cell cytotoxicity (combination index = 0.30), resulting in improved tumor cell killing. The present dual‐drug delivery system provides a promising strategy to develop controlled and targeted combination therapies for efficient cancer treatment.     

Biodegradable thermoresponsive polymeric magnetic nanoparticles: a new drug delivery platform for doxorubicin

The use of nanoparticles as drug delivery systems for anticancer therapeutics has great potential to revolutionize the future of cancer therapy. The aim of this study is to construct a novel drug delivery platform comprising a magnetic core and biodegradable thermoresponsive shell of tri-block-copolymer. Oleic acid-coated Fe₃O₄ nanoparticles and hydrophilic anticancer drug “doxorubicin” are encapsulated with PEO–PLGA–PEO (polyethylene oxide–poly d, l lactide-co-glycolide–polyethylene oxide) tri-block-copolymer. Structural, magnetic, and physical properties of Fe₃O₄ core are determined by X-ray diffraction, vibrating sample magnetometer, and transmission electron microscopy techniques, respectively. The hydrodynamic size of composite nanoparticles is determined by dynamic light scattering and is found to be ~36.4 nm at 25 °C. The functionalization of magnetic core with various polymeric chain molecules and their weight proportions are determined by Fourier transform infrared spectroscopy and thermogravimetric analysis, respectively. Encapsulation of doxorubicin into the polymeric magnetic nanoparticles, its loading efficiency, and kinetics of drug release are investigated by UV–vis spectroscopy. The loading efficiency of drug is 89% with a rapid release for the initial 7 h followed by the sustained release over a period of 36 h. The release of drug is envisaged to occur in response to the physiological temperature by deswelling of thermoresponsive PEO–PLGA–PEO block-copolymer. This study demonstrates that temperature can be exploited successfully as an external parameter to control the release of drug.     

Synthesis and Characterization of Multi-layered Core/Shell Particles by Sequential Emulsion Polymerization

A series of core/shell particles were prepared by sequential emulsion polymerization. The core/shell particles consisting of poly(methyl methacrylate) core grafted with using rubbery layer [poly(butyl acrylate)co-(styrene)] and then glassy layer [poly(methyl methacrylate)-co-(ethyl acrylate)] were prepared. The conditions which led to controlled particle size and morphology were discussed. A highly cross-linked structure was formed in both the cores and the shells by using a cross-linking agent, which could prevent the migration of hydrophobic shells to the inside of the particles. The core/shell particles were characterized by Fourier-transform infrared spectroscopy, solid state ¹³C-NMR. Thermogravimetric analysis (TGA) and differential scanning calorimeter (DSC) were used to determine the thermal stability and glass transition temperature of the core/shell particles, respectively. Results of the particle size analysis indicate that particle sizes were decreased when there is a rubbery layer as outer layer (0.44 μm) whereas it increases when there is a glassy layer as outer layer (324 μm). Scanning electron microscopy (SEM) also confirms the multi-layers formation in the polymer.     

Magnetic Field‐Controlled Release of Paclitaxel Drug from Functionalized Magnetoelectric Nanoparticles

Using magnetoelectric nanoparticles (MENs) for targeted drug delivery and on‐demand, field‐controlled release can overcome the control challenges of the conventional delivery approaches. The magnetoelectric effect provides a new way to use an external magnetic field to remotely control the intrinsic electric fields that govern the binding forces between the functionalized surface of the MEN and the drug load. Here, a study is reported in which the composition of the intermediate functionalized layer is tailored to control not only the toxicity of the new nanoparticles but also the threshold magnetic field for the dissociation of the drug from 30‐nm CoFe₂O₄–BaTiO₃ core–shell MENs in a controllably wide field range, from below 10 to over 200 Oe, as required to facilitate superficial, intermediate, and deep‐tissue drug delivery. Paclitaxel is used as a test drug. Specific experiments are described to maintain low toxicity levels and to achieve controllable dissociation of the drug molecules from the MENs' surface at three different subranges—low (<10 Oe), moderate (100 Oe), and high (>200 Oe)—by selecting the following 2‐nm intermediate layers: i) glycerol monooleate (GMO), ii) Tween‐20, and iii) ethyl‐3‐(3‐dimethylaminopropyl)carbodiimide (EDC). Field‐dependent FTIR, absorption spectra, atomic force microscopy, magnetometry analysis, zeta‐potential measurements, and blood circulation experiments are used to study the described functionalization effects.     

Temperature and Redox Dual‐Responsive Biodegradable Nanogels for Optimizing Antitumor Drug Delivery

The strategy to efficiently deliver antitumor drugs via nanocarriers to targeted tumor sites and achieve controllable drug release is attracting great research interest in cancer therapy. In this study, a novel type of disulfide‐bonded poly(vinylcaprolactam) (PVCL)‐based nanogels with tunable volume phase transition temperature and excellent redox‐labile property are prepared. The nanogels are hydrophilic and swell at 37 °C, whereas under hyperthermia (e.g., 41 °C), the nanogels undergo sharp hydrophilic/hydrophobic transition and volume collapse, which enhances the cellular uptake and drug release. The incorporation of disulfide bond linkers endows the nanogels with an excellent disassembly property in reducing environments, which greatly facilitates drug release in tumor cells. Nanogels loaded with doxorubicin (DOX) (DOX‐NGs) (DOX‐NGs) are stable in physiological conditions with low drug leakage (15% in 48 h), while burst release of DOX (92% in 12 h) can be achieved in the presence of 10 × 10^?3 m glutathione and under hyperthermia. The DOX‐NGs possess improved cell killing efficiency under hyperthermia (IC₅₀ decreased from 1.58 μg mL^?1 under normothermia to 0.5 μg mL^?1). Further, the DOX‐NGs show a pronounced tumor inhibition rate of 46.6% compared with free DOX, demonstrating that this new dual‐responsive nanogels have great potential as drug delivery carriers for cancer therapy in vivo.     

Comparative study of core–shell iron/iron oxide gold covered magnetic nanoparticles obtained in different conditions

In this study, we report the synthesis and characterization of the core–shell Fe covered with Au shells nanoparticles with mean diameters between 5 and 8 nm. The inverse micelles method was utilized to produce the samples. X-ray diffraction studies show that both core–shell systems have the expected crystalline structure. High resolution transmission electron microscopy and atomic emission spectroscopy techniques give additional information concerning the structure and composition of nanoparticles. An intermediate shell of amorphous oxidized iron was found between the magnetic Fe core and the external gold shell. The magnetic behavior of different core–shell samples shows no hysteresis loop indicating the superparamagnetic behavior of Fe@Au systems. The superparamagnetic behavior is also evidenced from FC and ZFC dependences of the magnetization versus temperature. By using the temperature dependence of the thermoremanent magnetization combined with magnetization versus applied magnetic field, the effective anisotropy constant was determined. The Fe/Au interface contribution to the effective anisotropy constant was calculated and discussed in relation with the combined shape and stress anisotropies.     

Two-dimensional Abrikosov-vortex microclusters: Shell structure and melting

Melting of two-dimensional Abrikosov-vortex microclusters in a type-II superconductor island with thickness less than the coherence length has been studied. Equilibrium configurations corresponding to local and global minima of potential energy for clusters with N=1–50 particles are calculated. The temperature dependences of the structure and of mean-square radial and angular vortex displacements are investigated. It is shown that vortex microclusters melt in two stages: first the frozen-out phase transfers to a state corresponding to rotational reorientation of crystalline shells with respect to one another, followed by a transition to a state with no radial order at a substantially higher temperature. The reason for this is that the barrier to shell rotation is significantly lower than that to radial breakdown of shells. Fiz. Tverd. Tela (St. Petersburg) 39, 1005–1010 (June 1997)     

Understanding of Polydopamine Encapsulation of Hydrophobic Curcumin for Pleiotropic Drug Nanoformulation

Pleiotropic drug nanoformulation promises the enhanced efficacy of nanomedicines on the market. In this study, it is demonstrated that polydopamine (PDA)-based drug encapsulation is a potential strategy for such nanoformulation, yet its mechanism remains poorly investigated. This study elucidates the mechanism of PDA-encapsulated Curnanoformulations (CP NPs) using hydrophobic curcumin (Cur) as a model drug via local dopamine (DA) polymerization on self-assembled Cur NPs. The formation of PDA-based drug nanoformulations with the core–shell structure is comprehensively investigated by controlling the key synthetic parameters, deepening the understanding of DA polymerization in the context of drugs. An intriguing morphology evolution is proposed to be the key event in the formation of CP NPs, attributing to the Cur diffusion from the core to the shell of CP NPs. Moreover, the morphological data can be used to guide the optimization of the PDA-based nanoformulation. In addition, the verification of soluble DA polymers in CP NPs hints at the heterogeneous nature of the excipient (i.e., PDA) of CP NPs, providing a cautionary view on the long-term safety of PDA-formulated drugs. In sum, this study would enable the pharmaceutical development of PDA-encapsulated Cur nanomedicines and generalize the PDA-based nanoformulation approach for a wider range of hydrophobic drugs.     

Multifunctional antitumor magnetite/chitosan-<Emphasis Type="SmallCaps">l</Emphasis>-glutamic acid (core/shell) nanocomposites

The development of anticancer drug delivery systems based on biodegradable nanoparticles has been intended to maximize the localization of chemotherapy agents within tumor interstitium, along with negligible drug distribution into healthy tissues. Interestingly, passive and active drug targeting strategies to cancer have led to improved nanomedicines with great tumor specificity and efficient chemotherapy effect. One of the most promising areas in the formulation of such nanoplatforms is the engineering of magnetically responsive nanoparticles. In this way, we have followed a chemical modification method for the synthesis of magnetite/chitosan-l-glutamic acid (core/shell) nanostructures. These magnetic nanocomposites (average size ≈340 nm) exhibited multifunctional properties based on its capability to load the antitumor drug doxorubicin (along with an adequate sustained release) and its potential for hyperthermia applications. Compared to drug surface adsorption, doxorubicin entrapment into the nanocomposites matrix yielded a higher drug loading and a slower drug release profile. Heating characteristics of the magnetic nanocomposites were investigated in a high-frequency alternating magnetic gradient: a stable maximum temperature of 46 °C was successfully achieved within 40 min. To our knowledge, this is the first time that such kind of stimuli-sensitive nanoformulation with very important properties (i.e., magnetic targeting capabilities, hyperthermia, high drug loading, and little burst drug release) has been formulated for combined antitumor therapy against cancer.     

Intermediate range order in supercooled water

ABSTRACT

The temperature dependence of the heights of the first and second x-ray diffraction peaks in supercooled water measured down to 244?K are found to display very different behaviours. While the first peak intensity remains essentially constant, the second peak increases strongly with decreasing temperature. In real space this is concomitant with the reduction of the number of non-bonded interstitial molecules between the first and second shells. It is found that although the first O-O shell in supercooled water is unchanged upon supercooling, the variations in intermediate range order are mainly associated with the growth of a predominantly tetrahedral network that is distinctly different from ice-Ih. Moreover, in this temperature regime we find a direct correlation between the height of the second diffraction peak and the intensity changes in the 2nd, 3rd, 4th and 5th peaks in the oxygen-oxygen pair distribution function.     

Surface modification of magnetite nanoparticle with azobenzene-containing water dispersible polymer

We here report the synthesis of magnetite nanoparticle (MNP) grafted with poly (ethylene glycol) methyl ether methacrylate (PEGMA)-azobenzene acrylate (ABA) statistical copolymer via atom transfer radical polymerization (ATRP) for drug entrapment and photocontrolled release. MNP was synthesized via thermal decomposition of iron (III) acetylacetonate in benzyl alcohol and surface functionalized to obtain ATRP initiating sites. Molar compositions of the copolymer on MNP surface were systematically varied (100:0, 90:10, 70:30, and 50:50 of PEGMA:ABA, respectively) to obtain water dispersible particles with various amounts of azobenzene. The presence of polymeric shell on MNP core was evidenced by transmission electron microscopy (TEM). Drug loading and entrapment efficiencies as well as drug release behavior of the copolymer–MNP complexes were investigated. It was found that when percent of ABA in the copolymers was increased, entrapment and loading efficiencies of prednisolone model drug were enhanced. Releasing rate and percent of the released prednisolone of the complex exposed in UV light were slightly enhanced as compared to the system without UV irradiation. This copolymer–MNP complex with photocontrollable drug release and magnetic field-directed properties is warranted for further studies for potential uses as a novel drug delivery vehicle.     

Optical properties of core/multishell CdSe/Zn(S,Se) nanocrystals

CdSe nanocrystals are now known as highly efficient fluorescent light sources. Their efficiency is however strongly dependent on the quality of the passivation layers. We show here that using a ZnSe/ZnS bi-layer shell leads to a larger photoluminescence yield than both ZnSe and ZnS simple shells. The intermediate ZnSe layer acts as a lattice parameter adaptation layer to improve on the core/shell interface quality, while the ZnS outer shell maximizes the exciton confinement.     

ON THE FREE VIBRATION OF STIFFENED SHALLOW SHELLS

A finite element analysis for free vibration behaviour of doubly curved stiffened shallow shells is presented. The stiffened shell element is obtained by the appropriate combinations of the eight-/nine-node doubly curved isoparametric thin shallow shell element with the three-node curved isoparametric beam element. The shell types examined are the elliptic and hyperbolic paraboloids, the hypar and the conoidal shells. The accuracy of the formulation is established by comparing some of the authors' results of specific problems with those available in the literature. Numerical results of additional stiffened shells are also presented to study the effects of various parameters of shells and stiffeners such as orientation (i.e., along x -/y -/both x and y directions), type (concentric, eccentric at top and eccentric at bottom) and number of stiffeners, stiffener depth to shell thickness ratio, and aspect ratio, shallowness and boundary conditions of shells on free vibration characteristics.     

Kinetics of the destruction of type I superconductivity by a current

The dynamics of the destruction of type I superconductivity in a wire by an overcritical current are studied. In a first time interval a normal region grows from the surface surrounding a superconducting cylindrical core which contracts until its radius reaches the radius of the intermediate state core according to London's picture of the static state. In a second step the intermediate state is built up between the normal shell and the superconducting core, which finally disappears. The onset of the intermediate state is a consequence of an instability of the interphase boundary.     

Acoustic breathing mode frequencies in cylinders,cylindrical shells and composite cylinders of general anisotropic crystals: Application to nanowires

We present here a study of the acoustic breathing modes for infinitely long cylinders, cylindrical shells and composite cylinders of general anisotropic crystals. We assume cylindrical anisotropy for the systems studied. We obtain expressions in closed form for their frequencies in the case of cylinders and cylindrical shells, valid for any anisotropic material, thus including up to 21 independent elastic constants. In the case of the lowest breathing mode of a thin cylindrical shell we obtain a simple analytical formula. This can be used to obtain a first estimate of the breathing mode frequency in nanotubes for any material. In the case of core–shell and composite cylinders we obtain the expressions for the secular determinant. We calculate the frequencies of the lowest acoustic breathing mode of Au, CdSe, InAs, GaAs, Ag and Bi nanowires obtained recently by different experimental groups. We also present results for the acoustic breathing modes of Au/Ag and ZnS/SiO₂ core–shell nanowires produced recently.     

Unconventional dynamics of vortex shells in mesoscopic superconducting corbino disks

The dynamics of vortex matter in mesoscopic superconducting Corbino disk is strongly influenced by the discrete vortex structure arranged in shells. While in previous works the vortex dynamics has been studied in large (macroscopic) and in very small mesoscopic disks (containing only few shells), in the intermediate-size regime it is much more complex and unusual, due to: (i) the competition between the vortex–vortex interaction and confinement and (ii) (in)commensurability among the vortex shells. We found that the interplay between these effects can result in a very unusual vortex dynamical behavior: (i) unconventional angular melting (i.e., propagating from the boundary, where the shear stress is minimum, towards the center) and (ii) unconventional dynamics of shells (i.e., the inversion of shell velocities with respect to the gradient driving force). This unusual behavior is found for different number of shells.     

Two-dimensional mesoscopic vortex clusters in a superconducting ring: Shell structure and melting

The structure and phase transitions in the mesoscopic system of vortices in a quasi-two-dimensional superconducting ring are investigated. The shell structure of the mesoscopic system of vortices is studied, and its variation with the number of vortices and the parameters of the superconducting ring is analyzed. Two mechanisms of formation of new shells in vortex clusters with an increasing number of vortices in an increasing magnetic field are discovered: the generation of a new shell in a cluster and the splitting of the internal shell into two shells. The melting of vortex clusters and their thermodynamic parameters are analyzed using the Monte Carlo method. It is found that the melting of shell-type clusters occurs in two stages, orientation melting taking place at the lower temperature (during which nearly crystalline adjacent shells start rotating relative to each other) and blurring of the vortex structure occurring at the higher temperature. The shells obtained by splitting upon an increase in the number of vortices do not participate in orientational melting. The two-stage form of melting is associated with the smaller height of potential barriers being surmounted during the rotation of shells relative to one another as compared to the barrier for vortices jumping from one shell to another.     

Temperature Controlled Sequential Gelation in Composite Microgel Suspensions

Depending on the volume fraction and interparticle interactions, colloidal suspensions can exhibit a variety of physical states, ranging from fluids, crystals, and glasses to gels. For microgel particles made of thermoresponsive polymers, both parameters can be tuned using environmental parameters such as temperature and ionic strength, making them excellent systems to experimentally study state transitions in colloidal suspensions. Using a simple two‐step synthesis it is shown that the properties of composite microgels, with a fluorescent latex core and a responsive microgel shell, can be finely tuned. With this system the transitions between glass, liquid, and gel states for suspensions composed of a single species are explored. Finally, a suspension of two species of microgels is demonstrated, with different transition temperatures, gels in a sequential manner. Upon increasing temperature a distinct core–sheath structure is formed with a primary gel composed of the species with lowest transition temperature, which acts as a scaffold for the aggregation of the second species.