A facile pathway to prepare enzymatically degradable microcapsules with tunable capsule shell properties

Dextran sulfate (DS)/poly-l-lysine (PLL) microcapsules are fabricated by an in situ coacervation method using DS-doped CaCO₃ microparticles as templates. Twinned superstructures or spherical CaCO₃ microparticles are produced depending on DS concentration in the starting solution. DS/PLL microcapsules with ellipsoidal or spherical outline are obtained after removal of templates in disodium ethylene diamine tetraacetate dehydrate (EDTA) without PLL. Their shell thickness and negative surface charges increase with the DS weight percentage in the templates. The surface potential of DS/PLL microcapsules, fabricated by core removal in an EDTA/PLL solution, can be easily tuned by altering PLL concentration in template removal solution. DS/PLL microcapsules fabricated by template removal in solution with or without PLL are both degraded by α-chymotrypsin, and different degradation profiles are observed because of shell thickness differences. DS/PLL may be used as transport vehicles for various compounds regardless of their charge sign in biomedical fields.     

Preparation and properties of chitosan chondroitin sulfate complex microcapsules

The chitosan (CHS) chondroitin sulfate (CS) complex microcapsules were prepared by emulsion-chemical crosslink method, with the chitosan and chondroitin sulfate as the wall materials and the low molecular weight heparin (LMWH) as the core materials. The microcapsules were characterized by Fourier transform infrared (IR) spectrometry, scanning electron microscope (SEM), size distribution and thermal analysis. The in vitro drug release behavior of the microcapsules was studied by spectrophotometry. The SEM and size distribution showed that the microcapsules were in the spherical form mostly in the size range of 20-80 microm. The IR spectrum indicated that there were electrostatic interactions between chitosan and chondroitin sulfate, with the sulfate group and free carboxyl group reacted with the amino groups of chitosan. The DSC result showed that the wall materials could protect the core materials of the microcapsules. The results of the release kinetics experiments of the microcapsules showed that the drug released slightly faster in acid media than in alkali ones.     

New Polyurethane/Docosane Microcapsules as Phase‐Change Materials for Thermal Energy Storage

Polyurethane microcapsules were prepared by mini‐emulsion interfacial polymerization for encapsulation of phase‐change material (n‐docosane) for energy storage. Three steps were followed with the aim to optimize synthesis conditions of the microcapsules. First, polyurethane microcapsules based on silicone oil core as an inert template with different silicone oil/poly(ethylene glycol)/4,4′‐diphenylmethane diisocyanate wt % ratio were synthesized. The surface morphology of the capsules was analyzed by scanning electronic microscopy (SEM) and the chemical nature of the shell was monitored by Fourier transform infrared spectroscopy (FT‐IR). Capsules with the silicone oil/poly(ethylene glycol)/4,4′‐diphenylmethane diisocyanate 10/20/20 wt % ratio showed the best morphological features and shell stability with average particle size about 4 μm, and were selected for the microencapsulation of the n‐docosane. In the second stage, half of the composition of silicone oil was replaced with n‐docosane and, finally, the whole silicone oil content was replaced with docosane following the same synthetic procedure used for silicone oil containing capsules. Thermal and cycling stability of the capsules were investigated by thermal gravimetric analysis (TGA) and the phase‐change behavior was evaluated by differential scanning calorimetry (DSC).     

十八烷/聚(St-MMA)相变微胶囊制备及表征

采用乳液聚合的方法,分别选取聚苯乙烯(PS)、聚甲基丙烯酸甲酯(PMMA)或苯乙烯和甲基丙烯酸甲酯的共聚物为壁材,正十八烷为芯材,十二烷基苯磺酸钠(SDBS)为乳化剂,制作相变储能微胶囊。用粒径分析仪、透射电子显微镜(TEM)、热重分析仪(TG)和示差扫描量热测试仪(DSC)对微胶囊的形貌、相变热性能和热稳定性分别进行表征。结果表明:壁材选取两者共聚物,当两种单体的比例为St∶MMA=1∶5,SDBS用量为1.5g(总质量的3%)时,微胶囊粒径大小均匀,粒子分散性好,壁材的包裹性好。微胶囊的放热峰为起始温度为27.3℃,终止温度为31.9℃,相变温度为28.9℃,相变焓为48.4J/g。TG表明长期使用温度不能超过131℃。IR分析微胶囊中含有芯材和壁材。这种十八烷/聚(St-MMA)相变微胶囊可以用于诸能材料。     

Biomimetic synthesis of raspberry-like hybrid polymer–silica core–shell nanoparticles by templating colloidal particles with hairy polyamine shell

The nanoparticles composed of polystyrene core and poly[2-(diethylamino)ethyl methacrylate] (PDEA) hairy shell were used as colloidal templates for in situ silica mineralization, allowing the well-controlled synthesis of hybrid silica core–shell nanoparticles with raspberry-like morphology and hollow silica nanoparticles by subsequent calcination. Silica deposition was performed by simply stirring a mixture of the polymeric core–shell particles in isopropanol, tetramethyl orthosilicate (TMOS) and water at 25 °C for 2.5 h. No experimental evidence was found for nontemplated silica formation, which indicated that silica deposition occurred exclusively in the PDEA shell and formed PDEA–silica hybrid shell. The resulting hybrid silica core–shell particles were characterized by transmission electron microscopy (TEM), thermogravimetry, aqueous electrophoresis, and X-ray photoelectron spectroscopy. TEM studies indicated that the hybrid particles have well-defined core–shell structure with raspberry morphology after silica deposition. We found that the surface nanostructure of hybrid nanoparticles and the composition distribution of PDEA–silica hybrid shell could be well controlled by adjusting the silicification conditions. These new hybrid core–shell nanoparticles and hollow silica nanoparticles would have potential applications for high-performance coatings, encapsulation and delivery of active organic molecules.     

Reversible polyelectrolyte capsules as carriers for protein delivery

A reversible drug delivery system based on spontaneous deposition of a model protein into preformed microcapsules has been demonstrated for protein delivery applications. Layer-by-Layer assembly of poly(allylamine hydrochloride) (PAH) and poly(methacrylic acid) (PMA) onto polystyrene sulfonate (PSS) doped CaCO₃ particles, followed by core removal yielded intact hollow microcapsules having a unique property to induce spontaneous deposition of bovine serum albumin (BSA) at pH below its isoelectric point of 4.8, where it was positively charged. These capsules showed reversible pH dependent open and closed states to fluorescence labeled dextran (FITC-Dextran) and BSA (FITC-BSA). The loading capacity of BSA increased from 9.1 × 10⁷ to 2.03 × 10⁸ molecules per capsule with decrease in pH from 4.5 to 3. The loading of BSA-FITC was observed by confocal laser scanning microscopy (CLSM), which showed homogeneous distribution of protein inside the capsule. Efficient loading of BSA was further confirmed by atomic force microscopy (AFM) and scanning electron microscopy (SEM). The interior capsule concentration was as high as 209 times the feeding concentration when the feeding concentration was increased from 1 to 10 mg/ml. The deposition was initially controlled by spontaneous loading mechanism at lower BSA concentration followed by diffusion controlled loading at higher concentration; which decreased the loading efficiency from 35% to 7%. Circular dichroism (CD) measurements and Fourier transform infrared spectroscopy (FTIR) confirmed that there was no significant change in conformation of released BSA in comparison with native BSA. The release was initially burst in the first 0.5 h and sustained up to 5 h. The hollow capsules were found to be biocompatible with mouse embryonic fibroblast (MEF) cells during in vitro cell culture studies. Thus these pH sensitive polyelectrolyte microcapsules may offer a promising delivery system for water soluble proteins and peptides.     

Multicompartmental Microcapsules with Orthogonal Programmable Two‐Way Sequencing of Hydrophobic and Hydrophilic Cargo Release

Multicompartmental responsive microstructures with the capability for the pre‐programmed sequential release of multiple target molecules of opposite solubility (hydrophobic and hydrophilic) in a controlled manner have been fabricated. Star block copolymers with dual‐responsive blocks (temperature for poly(N‐isopropylacrylamide) chains and pH for poly(acrylic acid) and poly(2‐vinylpyridine) arms) and unimolecular micellar structures serve as nanocarriers for hydrophobic molecules in the microcapsule shell. The interior of the microcapsule can be loaded with water‐soluble hydrophilic macromolecules. For these dual‐loaded microcapsules, a programmable and sequential release of hydrophobic and hydrophilic molecules from the shell and core, respectively, can be triggered independently by temperature and pH variations. These stimuli affect the hydrophobicity and chain conformation of the star block copolymers to initiate out‐of‐shell release (elevated temperature), or change the overall star conformation and interlayer interactions to trigger increased permeability of the shell and out‐of‐core release (pH). Reversing stimulus order completely alters the release process.     

Core‐shell structure microcapsules with dual pH‐responsive drug release function

We report dual pH‐responsive microcapsules manufactured by combining electrostatic droplets (ESD) and microfluidic droplets (MFD) techniques to produce monodisperse core (alginate)‐shell (chitosan) structure with dual pH‐responsive drug release function. The fabricated core‐shell microcapsules were size controllable by tuning the synthesis parameters of the ESD and MFD systems, and were responsive in both acidic and alkaline environment, We used two model drugs (ampicillin loaded in the chitosan shell and diclofenac loaded in the alginate core) for drug delivery study. The results show that core‐shell structure microcapsules have better drug release efficiency than respective core or shell particles. A biocompatibility test showed that the core‐shell structure microcapsules presented positive cell viability (above 80%) when evaluated by the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay. The results indicate that the synthesized core‐shell microcapsules were a potential candidate of dual‐drug carriers.     

Microgel-based engineered nanostructures and their applicability with template-directed layer-by-layer polyelectrolyte assembly in protein encapsulation

A novel strategy for the fabrication of microcapsules is elaborated by employing biomacromolecules and a dissolvable template. Calcium carbonate (CaCO(3)) microparticles were used as sacrificial templates for the two-step deposition of polyelectrolyte coatings by surface controlled precipitation (SCP) followed by the layer-by-layer (LbL) adsorption technique to form capsule shells. When sodium alginate was used for inner shell assembly, template decomposition with an acid resulted in simultaneous formation of microgel-like structures due to calcium ion-induced gelation. An extraction of the calcium after further LbL treatment resulted in microcapsules filled with the biopolymer. The hollow as well as the polymer-filled polyelectrolyte capsules were characterized using confocal laser scanning microscopy (CLSM), scanning electron microscopy (SEM), and scanning force microscopy (SFM). The results demonstrated multiple functionalities of the CaCO(3) core - as supporting template, porous core for increased polymer accommodation/immobilization, and as a source of shell-hardening material. The LbL treatment of the core-inner shell assembly resulted in further surface stabilization of the capsule wall and supplementation of a nanostructured diffusion barrier for encapsulated material. The polymer forming the inner shell governs the chemistry of the capsule interior and could be engineered to obtain a matrix for protein/drug encapsulation or immobilization. The outer shell could be used to precisely tune the properties of the capsule wall and exterior. [Diagram: see text] Confocal laser scanning microscopy (CLSM) image of microcapsules (insert is after treating with rhodamine 6G to stain the capsule wall).     

Thermal stability of microencapsulated epoxy resins with poly(urea-formaldehyde)

A series of microcapsules filled with epoxy resins with poly(urea-formaldehyde) (PUF) shell were synthesized by in situ polymerization, and they were heat-treated for 2 h at 100 °C, 120 °C, 140 °C, 160 °C, 180 °C and 200 °C. The effects of surface morphology, wall shell thickness and diameter on the thermal stability of microcapsules were investigated. The chemical structure and surface morphology of microcapsules were investigated using Fourier-transform infrared spectroscope (FTIR) and scanning electron microscope (SEM), respectively. The thermal properties of microcapsules were investigated by thermogravimetric analysis (TGA and DTA) and by differential scanning calorimetry (DSC). The thermal damage mechanisms of microcapsules at lower temperature (<251 °C) are the diffusion of the core material out of the wall shell or the breakage of the wall shell owing to the mismatch of the thermal expansion of core and shell materials of microcapsules. The thermal damage mechanisms of microcapsules at higher temperature (>251 °C) are the decomposition of shell material and core materials. Increasing the wall shell thickness and surface compactness can enhance significantly the weight loss temperatures (T_d) of microcapsules. The microcapsules with mean wall shell thickness of 30 ± 5 μm and smoother surface exhibit higher thermal stability and can maintain quite intact up to approximately 180 °C.     

Advanced design of t and pH dual‐responsive PDEAEMA–PVCL core–shell nanogels for siRNA delivery

The synthesis, characterization, and potential application as gene delivery systems of biodegradable dual‐responsive core–shell nanogels based on poly(2‐diethylaminoethyl) methacrylate (PDEAEMA) and poly(N‐vinylcaprolactam) (PVCL) are reported. These core–shell nanogels, having a PDEAEMA‐based core and a PVCL‐based shell, were synthesized by batch seeded emulsion polymerization. An indepth study of their swelling behavior was carried out, which presented a dual‐dependent thermo‐ and pH sensitivity. Core–shell nanogels synthesized formed complexes spontaneously through electrostatic interactions when mixing with small interfering RNA (siRNA) molecules. Moreover, the core–shell nanogel/siRNA complexes showed higher polyanion exchange resistance compared to that of the PDEAEMA‐based nanogel/siRNA complexes, indicating that the PVCL‐based shell enhanced the stability of the complexes. In vitro siRNA release profiles showed that siRNA release was controlled by the pH of the medium as well as by the crosslinking density of the PVCL‐based shell. These results indicate that dual‐responsive core–shell nanogels synthesized could be potentially useful as gene delivery systems. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 3203–3217     

alpha-Helical polypeptide microcapsules formed by emulsion-templated self-assembly

alpha-Helical peptide microcapsules were prepared by the emulsion-templated self-assembly of amphiphilic poly(gamma-benzyl L-glutamate)s (PBLG) 1. By mixing solutions of 1 in dichloromethane (in the form of a sodium salt) with water, oil-in-water emulsions were obtained. Spontaneous stripping of the dichloromethane phase caused a decrease in the diameter of the microdroplets and finally stable microcapsules formed. The microcapsules contain an inner aqueous phase as observed by confocal laser scanning microscopy (CLSM). Binding of hydrophobic pyrene molecules to the polypeptide shell was also demonstrated. The present polypeptide microcapsules are stable even after drying in air and they would serve as supramolecular vehicles for both hydrophobic and water-soluble molecules.     

Hollow nanoparticles prepared from pH‐responsive template polymer micelles

Water‐soluble crosslinked hollow nanoparticles were prepared using pH‐responsive anionic polymer micelles as templates. The template micelles were formed from pH‐responsive diblock copolymers (PAMPS‐PAaH) composed of the poly(sodium 2‐(acrylamido)‐2‐methylpropanesulfonate) and poly(6‐(acrylamido)hexanoic acid) blocks in an aqueous acidic solution. The PAMPS and PAaH blocks form a hydrophilic anionic shell and hydrophobic core of the core‐shell polymer micelle, respectively. A cationic diblock copolymer (PEG‐P(APTAC/CEA)) with the poly(ethylene glycol) block and random copolymer block composed of poly((3‐acrylamidopropyl)trimethylammonium chloride) containing a small amount of the 2‐(cinnamoyl)ethylacrylate photo‐crosslinkable unit can be adsorbed to the anionic shell of the template micelle due to electrostatic interaction, which form a core‐shell‐corona three‐layered micelle. The shell of the core‐shell‐corona micelle is formed from a polyion complex with anionic PAMPS and cationic P(APTAC/CEA) chains. The P(APTAC/CEA) chains in the shell of the core‐shell‐corona micelle can be photo‐crosslinked with UV irradiation. The template micelle can be dissociated using NaOH, because the PAaH blocks are ionized. Furthermore, electrostatic interactions between PAMPS and PAPTAC in the shell are screened by adding excess NaCl in water. The template micelles can be completely removed by dialysis against water containing NaOH and NaCl to prepare the crosslinked hollow nanoparticles. Transmission electron microscopy observations confirmed the hollow structure. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Chemo-enzymatic synthesis of raffinose-branched polyelectrolytes and self-assembly application in microcapsules

A novel biocompatible polyelectrolyte poly(vinyl raffinose-co-acrylic acid) (PRCA) containing a raffinose branch was prepared via redox polymerization using Fe(2+)/K(2)S(2)O(8)/H(2)O(2) starting from enzymatically-synthesized monomer: 1-O-vinyldecanedioyl raffinose. Copolymers with different monomer feed ratios were prepared and characterized with IR, NMR, and GPC. PRCA can be alternated with polycation to form microcapsules on a crystals template by electrostatic layer-by-layer technique. The multilayers of PRCA/poly(methacryloyloxyethyl dimethylbenzyl ammonium chloride) (PMBA) on quartz slides and PRCA/poly(dimethyldiallyl ammonium chloride) (PDDA) on acyclovir crystals template were fabricated and characterized with UV-Vis spectra, the microelectrophoretic measurement, and TEM. Hollow capsules can be formed after the removal of acyclovir crystals template in a buffer solution. The nano-capsule-carrying galactose residue is a potential targeting drug-controlled delivery systems.     

Preparation and characterization of poly(urethane–urea) microcapsules containing limonene. Kinetic analysis

The synthesis of poly(urethane–urea) shells (PUU) using poly(ethylene glycols) of different molecular weights and methylene-bis(4-cyclohexylisocyanate) was performed for the microencapsulation of limonene, using a step-growth polymerization process. The obtained microcapsules were structurally characterized by dynamic light scattering, optical microscopy, scanning electron microscopy, Fourier transform infrared spectroscopy, and thermogravimetric analysis. The results showed that the core–shell microcapsules had spherical shape, a mean diameter in between 10 and 20?µm, and characteristic urethane-urea bonds. Furthermore, the molecular weight of polyol influences the entrapment efficiency, which ranged from 38 to 55%. The release data were analyzed by applying the Korsmeyer–Peppas model.     

Robust polyazobenzene microcapsules with photoresponsive pore channels and tunable release profiles

Monodisperse silica particles coated with azobenzene polymer (PAzo) shell were synthesized through distillation precipitation polymerization. Robust PAzo microcapsules were obtained after selective removal of the silica templates by hydrofluoric acid (HF) etching. These PAzo microcapsules, confirmed by transmission electron microscopy (TEM) investigation, had excellent reversible photoisomerization with transformation between trans and cis isomers under ultraviolet (UV) and visible lights. Due to their compatibility with PAzo, acetonitrile would be trapped in the network of the shell during polymerization. Pore channels in the shell, confirmed by nitrogen adsorption–desorption test, would be produced after acetonitrile evaporation. Loading and release of rhodamine B (RhB) molecules in PAzo microcapsules were carried out and indicated that cis azobenzene showed larger pore diameter (named as “open switch”) under UV light which favored permeation of RhB molecules, while trans structure (named as “closed switch”) under visible light slowed down the process. In addition, both release profiles obeyed pure Fickian diffusion with a power law of t^0.42. Diffusion coefficient of RhB from PAzo microcapsules under visible light (1.47 × 10^?12 cm²/s) was lower than that under UV light (2.12 × 10^?12 cm²/s).     

pH/temperature dual stimuli-responsive microcapsules with interpenetrating polymer network structure

The microcapsules with interpenetrating polymer network (IPN) structure based on crosslinked poly (N-isopropylacrylamide) (PNIPAM) and crosslinked poly (acrylic acid) (PAA) were fabricated in a three-step process. Firstly, silica/PNIPAM core/shell composite particles were synthesized by thermo-initiated seed precipitation polymerization using 3-(trimethoxysilyl)propyl methacrylate modified silica colloidal particles as seeds and N-isopropylacrylamide and N,N′-methylenebisacrylamide (MBA) as monomer and crosslinker, respectively. Secondly, PAA network was incorporated into the shell of the composite particles by redox-initiated polymerization of acrylic acid and MBA entrapped in the PNIPAM network. Finally, the silica core of the composite particles was removed using hydrofluoric acid under certain condition to produce the microcapsules. The chemical compositions, their mass ratio, and particle sizes of the particles formed in each step were determined by Fourier transformation infrared spectroscopy, thermogravimetry, and dynamic laser light scattering (DLLS), respectively. The IPN structure of the microcapsules was identified by transmission electron microscopy (TEM) using uranyl acetate staining method, and their hollow structure was evidenced by TEM and scanning electron microscopy. Their temperature- or pH-dependent hydrodynamic diameters were measured by DLLS, and the results showed that the microcapules had both pH- and temperature-responsive properties, and the temperature-responsive component and the pH-responsive component inside the microcapsule shell had little interference with each other.     

Synthesis of polymer–inorganic patchy microcapsules with tunable patches

We introduce a facile and versatile approach for the formation of ball-like polymer–inorganic patchy microcapsules with a tunable shell by combining sol–gel chemistry of silica precursor and phase separation between the polymer and the precursor. Firstly, chloroform-in-water emulsion droplets containing poly(methyl methacrylate) (PMMA), silica precursor [tetraethyl orthosilicate (TEOS)] and co-surfactant sodium dioctyl sulfosuccinate (Aerosol OT or AOT) were prepared by shaking the mixture by hand. Due to the added AOT, water molecules diffuse into the chloroform droplets, and the tiny water droplets would coalesce gradually, triggering the formation of double emulsion droplets. Upon further solvent evaporation, the concentration of the polymer and the silica precursor in the oil shell of the double emulsions increases, leading to the phase separation between the polymer and the precursors (and partially formed silica through the hydrolysis and condensation of TEOS). Because of the confined geometry of the oil shell in the double emulsions, polymeric disc-like structures, stabilized by AOT, were dispersed in the silica precursors. Meanwhile, the silica precursor hydrolyzed and condensed when brought in contact with the aqueous solution, ultimately leading to the formation of a mineralized shell around the polymer domains and the hybrid patchy microcapsules. Effect of synthesis conditions, such as the amount of TEOS, AOT, and PMMA used, the pH value, and solvent evaporation rate on interfacial behavior of the solvent/water; and the morphology of the patchy microcapsules were investigated. Patchy microcapsules with tunable patch size and shape can be generated through tailoring the experimental parameters. Our study indicates that the hybrid patchy microcapsules can be formed by taking advantage of the sol–gel chemistry and the phase separation process, and the underlying generality of the synthesis procedure allows for a variety of applications, including drug storage, coatings, delivery, catalysis, and smart building blocks in self-assembling systems.     

Editorial Board: Electrophoresis 18'14

Electrophoresis 2014, 35, 2673–2680. DOI: 10.1002/elps.201400210 pH‐responsive microcapsules manufactured by combining electrostatic droplets (ESD) and microfluidic droplets (MFD) techniques to produce mono‐disperse core (alginate) ‐ shell (chitosan) structure with controlled drug release behavior. The fabricated core‐shell microcapsules have a pH‐controlled drug delivery function according to acidic and alkaline environment, and present positive biocompatibility, indicating their potential use in biological and biomedical applications, such as pH‐responsive drug‐delivery systems, scaffolding for bone tissues, and as an oral drug‐delivery vehicle.

     

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.