The undermentioned study is a sum-up of literature reviewed for the industry of microcapsules. More specifically the chief focal point of the reappraisal is the readying of polyelectrolyte microcapsules by the Layer-by-Layer method of industry. This method involves the back-to-back coating of by oppositely charged polyelectrolyte species onto a nucleus templet, which is so dissolved to give a hollow microcapsule. This method provides microcapsules with complex architecture, which can so be used in a assortment of applications. The stuff reviewed includes templets, polyelectrolytes and nucleus disintegration methods that can be used for readying of such microcapsules.
Methods of make fulling the nucleus with certain stuffs are besides discussed, as are mechanisms for release of the encapsulated stuff. There are besides assorted sensing methods available, which have besides been reviewed – some of which necessitating alteration of the polyelectrolyte wall during synthesis to guarantee sensing and word picture can be carried out accurately. Finally the readying and application of anisotropic ( or ‘Janus ‘ ) microcapsules is discussed, with the comparative deficiency of literature associating to this subject supplying an interesting country for possible farther research.
Encapsulation is a technique that has been used to great consequence throughout history in order to protect stuffs ( solid, liquid or gasses ) from a environing environment. The bulk of illustrations relate to the macroscopic universe, including illustrations such as the storage of nutrient, drink, volatile liquids and chemicals in assorted containers to forestall reactions with the environing air happening. Nature itself provides many illustrations of encapsulation such as eggs, seeds and fruits, all of which have different belongingss such as permeableness and composing based on the intended intent of the enclosed stuff.
Another peculiarly good illustration of encapsulation in nature is demonstrated in the composing of cells. Each cell has a flexible biolipid membrane enveloping the cell stuff, which acts as a permeable barrier capable of commanding what enters and leaves the cell. [ 1 ] The world is that there are an infinite figure of illustrations of encapsulation on a macroscopic graduated table. [ 2 ]
The rule of microencapsulation links to the same rule of protecting a stuff from the environment in which it is surrounded, nevertheless it relates to atoms with diameters on a µm graduated table.
Microcapsules are used in a broad assortment of applications including pharmaceuticals, cosmetics, agricultural industry, nutrient engineerings and fabrics industry. Microcapsules have besides been used for over 50 old ages in the printing industry, with an early application being sheets incorporating ink filled microcapsules which would tear when force per unit area was applied to them and therefore moving as a replacing for C transcript paper. [ 3 ] A better known application of microcapsules can be found in the production of many pharmaceutical merchandises for targeted drug bringing. In this illustration the nucleus stuff of the microcapsule is a specific drug which can be released over a certain period of clip via diffusion, by a force per unit area alteration doing the capsule to tear or by combination of the microcapsule wall with the mark cell wall.
[ 4 ] The method of drug bringing is dependent on the design of the shell of the microcapsule which can be tailored to the needed application, with certain belongingss being easier to accomplish than others. A comparatively easy and normally used method of forestalling release of drugs into the tummy and unwritten pits is the usage of gelatine capsules that are resilient to low pH. This belongings allows them to be digested further in the GI piece of land and the drug released at a specific point/time. The trouble comes when planing a microcapsule for sustained drug release over a designated clip period, which requires slow decomposition of the shell of the capsule in order to be achieved.
A recent country of involvement is the triggered release of drugs from microcapsules, which allows the release of drugs at an exact point e.g. when in contact with a cancerous cell or tissue. This engineering is still comparatively experimental with most triggered release mechanisms necessitating a triping system such as ultrasound [ 5 ] , external magnetic Fieldss and laser irradiation ( discussed in farther item subsequently in this reappraisal ) . Other attacks use self collection cysts and liposomes that form capsules under specific conditions. Another attack to accomplishing targeted bringing is the usage of polyelectrolyte capsules which are formed by the alternate deposition of oppositely charged electrolytes around a nucleus stuff such as polystyrene ( PS ) .
The nucleus can be dissolved one time the shell has been formed leting the hollow microcapsule nucleus to be loaded with a stuff for the designated intent. This layer-by-layer ( LbL ) technique of organizing polyelectrolyte capsules was foremost published about 20 old ages ago, [ 6 ] will be the primary focal point of this literature reappraisal which will besides discourse the patterned advances made in the field of microencapsulation every bit good as different types of microcapsules, methods of industry, stableness, application and sensing of such microcapsules.
It should be mentioned that there are other methods than the LbL technique, which can be used to make microcapsules without using polyelectrolytes. An illustration of an alternate method is the heterocoagulation of ‘large ‘ cationic microbeads ( used as the nucleus stuff ) , with little anionic polymer beads. The little anionic atoms surround the nucleus stuff and after an annealing procedure is applied, organize a dielectric shell around the nucleus stuff. This can so be dissolved if required to finish the synthesis of a hollow microcapsule. [ 7 ]
Polyelectrolyte Microcapsule Manufacture
As antecedently stated, the LbL technique of making microcapsules from colloidal atoms has been published for around 20 old ages. The rule behind this method is the back-to-back deposition of oppositely charged aqueous polyelectrolytes. This means that after initial deposition onto the nucleus templet, electrostatic interaction causes a bed of polyelectrolytes to organize around the templet as the oppositely charged species bond to the corresponding polyanion/cation.
Once the polyelectrolyte shell has been formed to the needed specification and the extra stuff removed if necessary, the nucleus can so be dissolved by utilizing an appropriate solution ( normally an acid ) depending on the initial nucleus templet. When compared to liposomes and other hollow nucleus atoms, microcapsules created by this peculiar method offer much greater permeableness, stableness and selectivity. This technique was ab initio used to make polyelectrolyte beds on planar surfaces, [ 8 ] nevertheless by utilizing a spherical templet such as a colloidal atom it is comparatively easy to use the method to this application. Figure 2 gives a conventional diagram of the LbL method.
There are two attacks which can be used to use this method, the first being where the right sums of polyelectrolyte stuff required to organize a bed are added at each measure, or the 2nd in which the polyelectrolytes are added in surplus. Both methods have advantages and disadvantages, the advantage of the first method is that the procedure is comparatively speedy since the polyelectrolytes adsorb onto the surface rapidly and no lavation or filtration is required in between rhythms. A farther advantage comes from the fact that there is no loss of polyelectrolytes during rinsing rhythms as exact sums are used for the synthesis.
The disadvantages of this method are that it can be hard to utilize precisely the right sum of polyelectrolytes necessary to organize a saturated shell and non to add the polyelectrolytes in surplus, which can take to the formation of polyelectrolyte composites and sums in solution. This issue is highly hard to get the better of and as a consequence the usage of polyelectrolytes in surplus is frequently chosen in favor of this method. A farther disadvantage is that as a effect of this method it is frequently common to lose the controlled superimposed construction.
[ 10 ] Despite the extra polyelectrolyte method being more favorable there are still several disadvantages associated with utilizing this method. One illustration being that since an surplus of stuff is used there is a demand for filtration/centrifugation and lavation after each measure in order to forestall a complex solution of polyelectrolytes organizing, which can frequently intend the procedure is really clip devouring. Removal of extra stuff by centrifugation can besides add farther complications as it can frequently take to loss of stuff, cause resuspension issues every bit good as doing it hard for little and low denseness atoms to successfully settle.
Polyelectrolytes and Templates Used
The polyelectrolytes used in the synthesis of the microcapsules will depend upon its intended application. Certain polyelectrolytes will give different belongingss to the microcapsule wall such as permeableness, stableness, pH opposition etc. compared to others.
In order for formation of a microcapsule wall, the stuff chosen must hold sufficient charged groups along the length of the unit. Polyelectrolytes should ideally be chosen where at least 50 % of the monomer units consisting them carry a functional charge. [ 11 ] Commonly used polyelectrolytes used for both microcapsules and on planar surfaces are Poly ( styrene sulfonate ) ( PSS ) , Poly ( allylamine ) ( PAH ) and Poly ( diallyldimethylammonium ) chloride ( PDA or PDADMAC ) . [ 12 ] While PAS and PAH are the most normally used and studied polyelectrolytes in this field, there have been other types of polyelectrolytes used such as polyacrylic acid ( PAA ) , Dextran sulphate, Nafion [ 13 ] and poly ( ethyleneimine ) in applications such as bringing of isobutylphenyl propionic acid and other drugs. [ 14 ] Table 1 illustrates some normally used polyelectrolytes. [ 15 ]
The pick of polyelectrolyte is evidently highly of import when planing a microcapsule, nevertheless before this choice is made it is necessary to take a nucleus stuff that will be used as a templet for the microcapsule to be built around. The nucleus templet itself must stay stable during the LbL polyelectrolyte deposition procedure and must be able to be to the full dissolved without impacting the construction or stableness of the multilayer shell. For obvious grounds it is besides discriminatory to hold a templet with spherical geometry.
The most normally used templet in LbL microcapsule synthesis is melamine-formaldehyde ( MF ) [ 16 ] . The grounds for this are that MF templates remain stable at pH values above 5, therefore leting polyelectrolyte deposition to be carried out at a favorable pH of 7, besides MF is readily dissolved in 0.1M hydrochloric acid. [ 17 ] One drawback of this nevertheless is that on disintegration of the MF nucleus, the protonated oligomers produced can non spread out every bit readily as would be desired. The size of the oligomers produced is straight linked to the molecular weight of the MF used in the synthesis, which can frequently differ rather significantly in a batch.
This causes the capsules to swell, bring forthing an increased osmotic force per unit area inside the capsule which in bend creates stress on the polyelectrolyte wall. If the capsule has many beds of polyelectrolyte ( & gt ; 12 ) so the capsule is frequently non able to shrivel back in size as the oligomers diffuse out, which can so take to tear of the capsule wall.15 Another drawback is that the MF nucleus can frequently go forth residues inside the microcapsule as a consequence of the strong interaction between MF and the interior PSS bed of polyelectrolyte. In the event of this happening, up to 50 % of the mass of the microcapsule can be attributed to these residues. MF templets are besides really expensive compared to other more readily available stuffs.
Other templets used include polystyrene, latex, silicon oxide, Ca carbonate ( CaCO3 ) [ 18 ] , manganese carbonate ( MnCO3 ) 16, metal nanoparticles every bit good as organic and inorganic crystals. No individual nucleus templet gives the exact demands, for illustration polystyrene nucleuss are dissolved with THF [ 19 ] , which can take to high mechanical emphasis on the capsule and go forth residues after disintegration, whereas silicon oxide atoms tend to aggregate when dissolved. Despite these drawbacks until new options are found so it is necessary to utilize these templets in such a manner that will give the maximal output of microcapsules possible.
Once the nucleus has been dissolved it is still possible to alter certain belongingss of the microcapsule. For illustration it is possible to alter the permeableness by the add-on of farther polyelectrolyte beds if required. [ 20 ]
Due to the high pertinence of microcapsules to the pharmaceutical industry there is an ever-increasing involvement in the development of utilizing polyelectrolytes that are of course happening species. An illustration of such polyelectrolyte is chitosan which is a of course happening additive polyose. Chitosan is besides biodegradable and non-toxic, which means that it is good suited to a pharmaceutical application.
The LbL synthesis of chitosan microcapsules requires a somewhat different man-made method compared to a microcapsule made of polyelectrolytes such as PSS and PAH. Zhang et Al. have demonstrated that it is possible to utilize the LbL method with chitosan and poly- ( acrylic acid ) ( PAA ) along with a silicon oxide templet to organize a polyelectrolyte shell, which can so be converted into a individual constituent chitosan shell if required. This is achieved by selectively cross-linking the chitosan in the microcapsule wall, taking the PAA constituent before disintegration of the nucleus templet. This method is demonstrated in Figure 3. [ 21 ]
Alteration of Polyelectrolyte Wall
It is possible to change the belongingss of the polyelectrolyte wall of the microcapsule in order to present elements of functionality. One such change is the add-on of a dye or fluorescent labelled stuff during the LbL synthesis of the microcapsule. This peculiar illustration can be used as a method of sensing and will be discussed in farther item subsequently in this reappraisal.
Use of Magnetic Particles
Another utile alteration of the polyelectrolyte wall is the incorporation of magnetic atoms during synthesis of the microcapsule. This allows control of the placement of the microcapsules when placed in a magnetic field. This is a peculiarly interesting attack that could be potentially applied to many medical applications such as targeted drug bringing systems. This in pattern would affect using the magnetic atoms nowadays in the shell to concentrate the microcapsules in the coveted place, followed by the usage of optical maser irradiation to alter the permeableness of the shell wall i.e. let go ofing the drug or other stuff stored within the nucleus ( Illustrated in Figure 4 ) . In add-on to this, the usage of magnetic atoms really makes the microcapsule wall sensitive to laser radiation, therefore doing the effectivity of this combination of techniques possible. [ 26 ]
Gorin et Al. have demonstrated that it is possible to make functionalised microcapsules that are sensitive to laser radiation by the incorporation of magnetic and gilded nanoparticles into the polyelectrolyte shell. This method involves the usage of a CaCO3 nucleus templet along with poly ( L-arginine ) ( PArg ) and Dextran sulfate as polyelectrolytes in LbL deposition. Once completed, magnetic nanoparticles can so be added to the polyelectrolyte wall by submergence of the microcapsule into diluted H2O suspensions of the nanoparticles in a ratio of 1:50.
Gold nanoparticles can besides be added by submergence of the microcapsules in an undiluted solution. [ 27 ] While the consequences from these experiments show success in this application, there are besides several drawbacks associated such as the inclination for the magnetic nanoparticles to roll up and non be distributed homogenously throughout the polyelectrolyte shell. This means that farther research is required in order to do efficient usage of magnetic atoms in microcapsules.
Another attack to utilizing magnetic nanoparticles with microcapsules is the add-on of magnetic atoms to the nucleus of the microcapsule in order for it to be manipulated by a magnetic field. This can be achieved by complexation of a PAH with an inorganic salt with magnetic belongingss, i.e. ZnFe2O4, MnFe2O4 etc. before lodging the composites into the hollow nucleus of a polyelectrolyte microcapsule. By changing the pH of the system it is possible to accomplish precipitation of the magnetic atoms inside the nucleus of the microcapsule. [ 28 ] The method of encapsulating a polyelectrolyte such as PAH is discussed in farther item subsequently in this study.
A different method to integrate magnetic atoms with microcapsules is to surface the nucleus templet with magnetic atoms prior to LbL synthesis. This can be achieved incubating MF particles together with magnetite atoms ( Fe3O4 ) in order to give them a magnetic coating, which so leaves a magnetic surfacing merely on the innermost polyelectrolyte bed once the nucleus has been dissolved. Figure 5 shows a Transmission Electron Microscope ( TEM ) image of a microcapsule synthesised by this method. [ 29 ]
The usage of an alternating magnetic field can besides be applied to originate a triggered release mechanism.
Filling of Microcapsules
The filling of the hollow nucleus provides the following challenge in the industry of a utile microcapsule. The most straightforward method is to utilize a nucleus templet made of the stuff that will finally be used in the concluding microcapsule. This prevents several challenges, as antecedently mentioned the choice of the nucleus restricts the polyelectrolytes that can be used and visa versa. A common job that arises when make fulling microcapsules with low molecular weight species is a inclination for the stuff non to precipitate in the nucleus of the microcapsule, but alternatively precipitate either onto the polyelectrolyte walls or in the solution that is being used.
One method used in order to make full the nucleus is similar to a method antecedently discussed for magnetic atoms, and involves the add-on of the coveted end point nucleus stuff e.g. a polymer, onto the nucleus templet prior to synthesis. Igor et Al. have shown that it is possible to fix microcapsules in this manner by the initial complexation of a polymer with multivalent ions such as Y3+ , which are so deposited onto the nucleus templet.
Conventional LbL synthesis is so carried out to organize the microcapsule. Due to the low stableness of the polymer/metal ion composites these readily break down after the nucleus has been dissolved. This so leaves the polymer in the nucleus of the microcapsule which is non capable of spreading out. The strategy for this synthesis is shown in Figure 6. [ 30 ]
A drawback with this technique is that due to the comparative big size of the metal ions used for complexation, they are frequently excessively big to spread out of the microcapsule, intending that they excessively become at bay within the nucleus. This can hold different deductions depending on the intended usage for the microcapsule itself.
Another method of make fulling microcapsules is known as the ‘ship in a bottle technique ‘ . [ 31 ] This involves the synthesis of copolymers inside the microcapsule from monomers deposited into the nucleus. Dahne et Als have demonstrated a practical manner to accomplish the polymerization of Na cinnamene sulfonate ( SS ) into PSS. The first measure in this procedure is to synthesize a conventional polyelectrolyte microcapsule utilizing PSS and PAH polyelectrolytes together with a MF nucleus templet, which should so be dissolved utilizing 0.1M HCl. The polyelectrolytes are so incubated in solution together with the monomer units. These monomer units ( plus a needed instigator – such as K peroxodisulfate ) diffuse through the polyelectrolyte wall and into the nucleus, which when heated Begin polymerizing.
Subsequent rinsing rhythms allows the polymer-filled microcapsules to be isolated from the matrix. There are several issues associated with utilizing this method, one of those being that due to come up charge bing on the microcapsule wall it is common for the instigator to be unevenly distributed, intending that it is common to detect polymers being synthesised onto the capsule wall or within the wall itself. This means that the overall belongingss of the microcapsule are altered which so has deductions when trying to utilize it for its intended application and can frequently take to tearing of the polyelectrolyte wall.
A farther method that can be used to encapsulate little sums of stuff is altering the conditions around the microcapsule, for illustration the pH, in order to change the permitivity of the polyelectrolyte wall. It is besides possible to encapsulate enzymes in microcapsules to make a biologically active species. This normally requires the LbL synthesis to be conducted onto the enzyme ( or sums of the enzyme ) itself, which can frequently do certain practical troubles. Zhao et Al. have successfully encapsulated horseradish peroxidase ( HRP ) into polyelectrolyte microcapsule by first fade outing the HRP enzyme along with CaCl2 into the CaCO3 nucleus templet. LbL synthesis of the polyelectrolyte bed was so carried out utilizing PAH and PSS, before fade outing the nucleus with EDTA and go forthing the enzyme contained within the microcapsule, as illustrated in the strategy shown in Figure 7.
This method of make fulling the nucleus is non sole to enzyme substrates and one time the polyelectrolyte nucleus is established this gives a sensitive selectivity to the charge of species that are able to pervade the microcapsule wall. For illustration if the polyelectrolyte used in the nucleus is negatively charged ( such as PSS ) , so this will selectively let positively charged species to go through through the capsule wall and will show repulsive force to other negatively charged species, as demonstrated in Figure 8. [ 32 ]
The Donnan equilibrium relates to the different chemical composings between the nucleus of a microcapsule and the solution in which the capsule is immersed. [ 33 ] The filling of the nucleus by this electrostatically selective method can be used to switch the equilibrium depending on the species added to solution. An issue arises when trying to make full the microcapsule with a high molecular weight species that are excessively big to traverse the permeable polyelectrolyte wall. A technique to temporarily increase the permeableness of the microcapsule wall to such molecules is to utilize an acetone/water mixture ( typically about 30 % ) which leaves the polyelectrolyte shell in an ‘open province ‘ ( Figure 9 B ) , leting big molecules to be added to the nucleus. Dilution of the solution with pure H2O ( Figure 9 C ) followed by rinsing so returns the permeableness of the capsule wall to its original province ( Figure 9 D ) . [ 34 ]
Precipitation can besides be used to selectively make full a microcapsule nucleus. This can be achieved by the add-on of a polyelectrolyte e.g. PSS to the solution incorporating the microcapsules with a low salt concentration. The polyelectrolyte can non perforate the capsule wall and so the pH inside the nucleus remains changeless, whereas the pH in the encompassing solution is altered depending on the dissociation equilibrium. The following measure involves add-on of the new nucleus stuff, such as a drug, to the solution.
The pH of the solution can so be changed so that pH of hollow nucleuss of the microcapsules have more favorable value, which besides relates to the antecedently mentioned Donnan equilibrium. Once the pH has been adjusted precipitation of the drug into the microcapsule will get down to happen. Once this procedure is started, stuff capable of perforating the microcapsule wall will efficaciously be ‘sucked ‘ into the nucleus until the volume is filled wholly. [ 35 ] The reversal of this procedure is known as disintegration and can be used as a controlled release mechanism for the microcapsules.
There have been several methods of let go ofing an encapsulated stuff discussed already in this reappraisal. This subdivision is indented to summarize those methods already mentioned and discussed. The intended release mechanism should be considered when planing the capsule itself, which evidently links straight to the indented application of the microcapsule. The two types of release mechanisms available are instant release i.e. bursting of the microcapsule, and sustained release over a designated clip period.
In the illustration of microcapsules incorporating a curative compound or drug, burst release is ideally suited when the compound will be straight absorbed into the mark call i.e. intracellular consumption. However if the drug compound is either toxic in high concentrations or required at a peculiar sustained degree ( as is the instance for many medical conditions such as schizophrenic disorder [ 36 ] ) , so a sustained release mechanism is best suited to such applications. Burst release can be achieved by utilizing an external triping mechanism such as application of a magnetic field, optical maser or light irradiation or pH change, depending on the composing of the capsule and the environment that it is in.
Sustained release, as antecedently mentioned is a more ambitious mechanism to accomplish. This is possible by utilizing a microcapsule wall that either additions in permeableness or degrades over a period of clip, therefore supplying changeless release of the drug contained in the nucleus. [ 37 ] Changing of environmental conditions such as pH may be used to originate these alterations in the microcapsule wall, although this must be done with a high degree of sensitiveness in order to non trip a explosion release mechanism. Changing ionic strength allows an excess method of accomplishing sustained release of the nucleus stuff.
Stability of Microcapsules as a Consequence of Filling
There have been several possible methods discussed that can be used to make full a microcapsule with a material/species of involvement. Once the nucleus has been filled with the concluding stuff such as a drug or polymer unit, this can hold an consequence on the overall stableness of the microcapsule. When the microcapsules are filled with a high concentration of solution so swelling of the capsule will happen, and if the concentration inside the nucleus becomes excessively high so the polyelectrolyte wall will necessarily tear. The consequence that the concentration in the nucleus has on the stableness of the shell has been demonstrated where a PSS/PAH microcapsule is filled with a 0.5M PSS solution and the size of the microcapsule really reduces by about 15 % in comparing to the tantamount hollow capsule.
In contrast to this, make fulling the nucleus with a 1M PSS solution via the ‘ship in a bottle ‘ method of assembly swell by a factor of about 4 compared to their original size ( Figure 10b ) before rupturing of the microcapsule wall occurs. The puffiness is known to be a consequence of internal osmotic force per unit area induced by the Na+ counterions present inside the capsule. If conceited capsules are treated with a concentrated solution of PDA ( 2M ) , so it is possible to cut down the swelling due to the increasing of the osmotic force per unit area in the environing solution ( Figure 10c ) . 31
As antecedently mentioned, a similar state of affairs can besides originate before the microcapsule is filled, as consequence of the initial nucleus templet being dissolved. For illustration when an MF nucleus is dissolved the end point oligomers frequently become at bay and do the microcapsule to swell and in some instances rupture if the concentration is above a critical degree.
Presence of polyelectrolyte in the solution incorporating the microcapsules can besides hold an consequence on the stableness of the capsule itself. For illustration if a high concentration of PSS is present in the surrounding environment it creates an increased external osmotic force per unit area since it can non perforate the polyelectrolyte wall. At high concentrations, this mechanical emphasis on the outer beds of polyelectrolyte can take to clasping ensuing in distortion of the microcapsule ( Figure 11 ) . 35
Detection, Measurement and Characterisation of Microcapsules
A normally used method of observing microcapsules is the usage of fluorescent species that can be added to the microcapsule and so observed utilizing fluorescence microscopy. The usage of confocal optical maser scanning microscopy for the sensing of fluorescently labelled species has been investigated in the class of this reappraisal [ 38 ] . The fluorescent stuff can either be added straight to the nucleus of the microcapsule, or incorporated into the polyelectrolyte multilayer.
In order to add a fluorescent stuff to the nucleus of a microcapsule, it is necessary to bond the species to a molecule that will readily pervade the polyelectrolyte shell and be deposited in the nucleus. An illustration of this method involves the labelling of PAA with fluorescin ( giving PAAAF ) , which can be achieved by covalently adhering aminofluorescein to the PAA constituent via the formation of amide bonds. [ 39 ] Once synthesized, this labeled polyelectrolyte can be captured within CaCO3 nucleus templets, which can so be used in the synthesis of PAH/PSS microcapsules.
After fade outing the nucleus with 0.1M HCl and several rinsing rhythms the PAAAF remains encapsulated in the polyelectrolyte shell. Confocal optical maser scanning microscopy can so be used to detect and mensurate the end point microcapsules ( Figure 12 ) . [ 40 ] It is besides possible to surface the microcapsule with a nano polyelectrolyte movie if necessary to forestall leaking of the fluorescent stuff from the capsule.
In a similar method to this, it is possible to flourescently label the polyelectrolyte wall of the capsule as opposed to the nucleus. This method of fluorecent labelling gives CLSM images like those shown in Figure 10a.
Another simple method to detect microcapsules is the add-on of a dye. This is possible by adding a dye to the majority solution that the capsules are stored in that is able to pervade the polyelectrolyte wall. Observation can so be made utilizing either CLSM or optical microscopy.32 In add-on to this, dyes besides have the added grade of functionality of supplying sensitiveness of the microcapsules to laser radiation. This makes dyes a utile tool for both sensing and targeted release.
Scaning negatron microscopy ( SEM ) , transmittal negatron microscopy ( TEM ) and atomic force microscopy ( AFM ) are normally used in the survey of polyelectrolyte microcapsules. These techniques provide clear high-resolution images of the microcapsules leting measuring and farther word picture to be carried out. The pick of technique used is based on the results/images required, for illustration if high-resolution three dimensional images are required for word picture the SEM should be chosen. Figure 13 shows the assorted images obtained from each of the techniques.8
Small-angle neutron sprinkling ( SANS ) is a technique that has late been developed that allows accurate word picture of multilayer microcapsules. SANS can be used for aqueous, solid or gas stage samples, intending that no sample pre-treatment such as drying is required prior to microcapsule word picture. The rules behind this method are instead complex and will non be discussed in deepness for the intent of this reappraisal. Experimental consequences have shown that SANS it is an highly utile technique in the finding of the thickness of the polyelectrolyte shell every bit good as the diameter of the nucleus. [ 41 ] The method in itself is similar to small-angle X-ray sprinkling ( SAXS ) , which can be used as a complimentary technique if construction finding is required.
The fiction of microparticles and microcapsules with varied functionality has been the topic of increasing involvement in recent old ages. [ 42 ] A manner of accomplishing these belongingss is to bring forth aniotropic microcapsules – normally referred to as ‘Janus ‘ microcapsules. The Roman God Janus is normally depicted as holding a caput comprised of non indistinguishable dorsum to endorse faces, so for this ground the term is used to depict microcapsules/particles which have hemispheres that are non chemically indistinguishable. Anisotropic facets can originate from the microcapsule ‘s form or surface belongingss.
For illustration it has been shown that microparticles with fresh anisotropic magnetic belongingss can be assembled and manipulated to great consequence by the usage of an external magnetic field. [ 43 ] This is an interesting and potentially utile rule that could potentially be applied successfully to hollow/filled polyelectrolyte microcapsules. Pero et Al. have demonstrated several methods of manufacturing spherical microstructues with anisotropic/Janus belongingss including masking/unmasking techniques ( Figure 14a ) , usage of reactive directional fields/fluxes ( Figure 14b ) , microcontact printing ( Figure 14c ) and the usage of interfaces leting partial exposure of the atoms to a reactive medium ( Figure 14d ) . [ 44 ]
The challenge faced when manufacturing anisotropic micro constructions is keeping double functionality and hardiness when insulating the microcapsules and when dehydrating/re-hydrating them.
LbL fabricated polyelectrolyte microcapsules have been successfully modified to bring forth anisotropic microcapsules, nevertheless literature associating to such ‘Janus ‘ capsules is comparatively scarce. One method used to partly modify the surface of microcapsules is the usage of atom lithography. This method involves bring forthing the LbL polyelectrolyte microcapsules which are so fixed onto a masking substrate so that merely 5 % of the capsule surface country is in contact with the substrate itself. Nanoparticles are so used to make a shell around the non-masked surface of the microcapsules, which consequences in the formation of a barrier shell. When the microcapsule is desorbed from the dissembling substrate the consequence is the production of microcapsules that have a functionalised nanoscale spot covering 5 % of their surfaces ( Figure 15 ) . [ 45 ]
The hardiness and stableness of the microcapsules is maintained by the nanoparticle shell which besides contains fluorescent stuff. This belongings besides allows for sensing and word picture of the microcapsules with fluorescence microscopy, which clearly shows the little functionalised spot on the capsule surface ( Figure 16 ) .
Another method that has been used to bring forth anisotropic microcapsules is the add-on of multi-layer coatings onto the polyelectrolyte shell, followed by subsequent polymer-on-polymer stamping ( POPS ) . This method consists of first fixing a polyelectrolyte microcapsule via the LbL method ( Figure 17a ) , which are so adsorbed onto a glass substrate ( Figure 17b ) . The following measure involves add-on of farther polyelectrolyte to the microcapsule via a POPS method, which due to the microcapsules being adsorbed onto the glass surface consequences in merely the top hemisphere deriving farther polyelectrolyte ( Figure 17c ) . This measure can so be repeated as necessary to lodge the needed sum of polyelectrolyte to be deposited, before desorbing the atoms from the glass surface and fade outing the nucleus templet ( Figure 17 ) . [ 46 ]
Extra alteration of the anisotropic microcapsules produced by this method can so be conducted by the usage of different polyelectrolytes, extra polymers or grafting of functionalised ironss with reactive terminals.
Decisions and Outlook
After this reappraisal it is clear that polyelectrolyte microcapsules are an of import and utile method of transporting stuffs of involvement to a specific mark location. The LbL method of industry is a well-developed method that allows great flexibleness in the design and synthesis of different polyelectrolyte systems. It is good demonstrated that the polyelectrolyte walls of the ensuing microcapsules can be modified further in order to command permeableness, or for external use e.g. by a magnetic field. There are legion methods that have been used to make full the hollow nucleus with the species of involvement, which finally dictates the method ( s ) that can be used.
Filling of the nucleus with in bend has an consequence on the overall stableness on the microcapsule, which is straight linked to the volume and stuff that is encapsulated. The release of the encapsulated stuff can be either sustained over a certain period of clip, or in a individual explosion to present the full contents of the microcapsule at one time. The polyelectrolyte shell can be tailored to give the coveted release mechanism, which depends on the intended application of the microcapsule. Numerous signifiers of microscopy are available for the sensing or word picture of microcapsules that have been prepared.
It is besides apparent from the deficiency of literature available that the readying and application of anisotropic/Janus microcapsules is non a good published country of research. As a consequence this leaves a important country for farther probe into such microcapsules, including industry, belongingss, functionality etc.
List of Mentions
H. Qiang, C. Yue, L. Junbai, Molecular assembly and application of biomimetic microcapsules, Chem. Soc. Rev. , 2009, 38, 2292 – 2303.
A. R. Hemsley, P. C. Griffiths, Architecture in the microcosm: biocolloids, self-assembly and pattern formation, Philos. Trans. R. Soc. London Ser. A. , 2000, 358, 547 – 564.
L. Schleicher, B. K. Green, US Patent 2730456, 1956.
K. Bala, P. Vasudevan, Polymeric Microcapsules for Drug Delivery, Journal of Macromolecular Science-Chemistry, 1981, A16, 819 – 827.
T. Neenan, M. Marcolongo, R.F. Valentini, Ultrasound-triggered drug bringing with contrast imagination: consequence of microencapsulation method, Biomedical Materials – Drug Delivery Implants and Tissue Engineering, 1999, 550, 113 – 118.
G. Decher, J.D. Hong, Buildup of Ultrathin Multilayer Films by a Self-Assembly Process.1. Back-to-back Adsorption of Anionic and Cationic Bipolar Amphiphiles on Charged Surfaces, Makromol. Chem. , Macromol. Symp. , 1991, 46, 321 – 327.
H. Li, E. Kumacheva, Core-shell particles with conductive polymer nucleuss, Colloid Polym Sci. , 2003, 281, 1 – 9.
G. Decher, Fuzzy Nanoassemblies: Toward Layered Polymeric Multicomposites, Science, 1997, 277, 1232 – 1237.
E. Donath, G. B. Sukhorukov, F. Caruso, S. A. Davis, H. Mohwald, Novel Hollow Polymer Shells by Colloid-Templated Assembly of Polyelectrolytes, Angew. Chem. Int. Ed. 1998, 37, 2201-2205.
A. Voigt, E. Donath, H. M & A ; ouml ; hwald, Preparation of microcapsules of strong polyelectrolyte twosomes by one-step complex surface precipitation, Macromol. Mater. Eng. , 2000, 282, 13 – 16.
K. Glinel, A. Moussa, A. Jonas, A. Laschewsky, Influence of Polyelectrolyte Charge Density on the Formation of Multilayers of Strong Polyelectrolytes at Low Ionic Strength, Langmuir, 2002, 18, 1408 – 1412.
C. Y. Gao, S. Leporatti, S. Moya, E. Donath, H. M & A ; ouml ; hwald, Stability and Mechanical Properties of Polyelectrolyte Capsules Obtained by Stepwise Assembly of Poly ( styrenesulfonate Na salt ) and Poly ( diallyldimethyl ammonium ) Chloride onto Melamine Resin Particles, Langmuir, 2001, 17, 3491 – 3495.
Z. Dai, H. M & A ; ouml ; hwald, Highly Stable and Biocompatible Nafion-Based Capsules with Controlled Permeability for Low-Molecular-Weight Species, Chem. Eur. J. 2002, 8, 4751 – 4755.
X. P. Qiu, E. Donath, H. M & A ; ouml ; hwald, Permeability of Ibuprofen in Various Polyelectrolyte Multilayers, Macromol. Mater. Eng. 2001, 286, 591 – 597.
L. Dahne, C.S. Peyratout, Tailor-Made Polyelectrolyte Microcapsules: From Multilayers to Smart Containers, Angew. Chem. Int. Ed. 2004, 43, 3762 – 3783.
A. Wang, C. Tao, Y. Cui, L. Duan, Y. Yang, J. Li, Assembly of environmental sensitive microcapsules of PNIPAAm and alginate acid and their application in drug release, Journal of Colloid and Interface Science, 2009, 332, 271 – 279.
C. Gao, S. Moya, H. Lichtenfeld, A. Casoli, H. Fiedler, E. Donath, H. M & A ; ouml ; hwald, The Decomposition Process of Melamine Formaldehyde Cores: The Key Step in the Fabrication of Ultrathin Polyelectrolyte Multilayer Capsules, Macromol. Mater. Eng. , 2001, 286, 355 – 361.
W.C.Mak, K.Y.Cheung, D.Trau, Influence of Different Polyelectrolytes on Layer-by-Layer Microcapsule Properties: Encapsulation Efficiency and Colloidal and Temperature Stability, Chem. Mater. , 2008, 20, 5475 – 5484.
M.K. Park, C. Xia, R.C. Advincula, Cross-Linked, Luminescent Spherical Colloidal and Hollow-Shell Particles, Langmuir, 2001, 17, 7670 – 7674.
G. Ibarz, L. D & A ; auml ; hne, E. Donath, H. M & A ; ouml ; hwald, Resealing of Polyelectrolyte Capsules after Core Removal, Macromol. Rapid Commun. , 2002, 23, 474 – 478.
Y. Zhang, Y. Guan, S. Zhou, Single Component Chitosan Hydrogel Microcapsule from a Layer-by-Layer Approach, Biomacromolecules 2005, 6, 2365 – 2369.
S.Y. Yang, D. Lee, R.E. Cohen, M.F. Rubner, Bioinert Solution-Cross-Linked Hydrogen-Bonded Multilayers on Colloidal Particles, Langmuir 2004, 20, 5978 – 5981.
Z. Zhao, Q. Chen, J.I. Anzai, Horseradish peroxidase microcapsules based on layer-by-layer polyelectrolyte deposition, Journal of Environmental Sciences Supplement, 2009, S135 – S138.
R. Georgieva, S. Moya, M. Hin, R. Mitl & A ; ouml ; hner, E. Donath, H. Kiesewetter, H. M & A ; ouml ; hwald, H. B & A ; auml ; umler, Permeation of Macromolecules into Polyelectrolyte Microcapsules, Biomacromolecules, 2002, 3, 517 – 524.
D.B. Shenoy, A.A. Antipov, G.B. Sukhorukov, Layer-by-Layer Engineering of Biocompatible, Decomposable Core-Shell Structures, Biomacromolecules, 2003, 4, 265 – 272.
A.G. Skirtach, A.A. Antipov, D.G. Shchukin and G.B. Sukhorukov, Remote Activation of Capsules Containing Ag Nanoparticles and IR Dye by Laser Light, Langmuir, 2004, 20, 6988-6992.
D.A. Gorin, S.A. Portnov, O.A. Inozemtseva, Z. Luklinska, A.M. Yashchenok, A.M. Pavlov, A.G. Skirtach, H. M & A ; ouml ; hwald, G.B. Sukhorukov, Magnetic/gold nanoparticle functionalized biocompatible microcapsules with sensitiveness to laser irradiation, Phys. Chem. Chem. Phys. , 2008, 10, 6899 – 6905.
D.G. Shchukin, I.L. Radtchenko, G.B. Sukhorukov, Synthesis of Nanosized Magnetic Ferrite Particles Inside Hollow Polyelectrolyte Capsules, J. Phys. Chem. B, 2003, 107, 86 – 90.
A. Voigt, N. Buske, G.B. Sukhorukov, A.A. Antipov, S. Leporatti, H. Lichtenfeld, H. Baumler, E. Donath, H. M & A ; ouml ; hwald, Novel polyelectrolyte multilayer micro- and nanocapsules as magnetic bearers, Journal of Magnetism and Magnetic Materials, 2001, 225, 59 – 66.
I.L. Radtchenko, G.B. Sukhorukov, H. M & A ; ouml ; hwald, Incorporation of supermolecules into polyelectrolyte micro and nanocapsules via surface controlled precipitation on colloidal atoms, Colloids Surf. A, 2002, 202, 127 – 133.
L. Dahne, S. Leporatti, E. Donath, H. M & A ; ouml ; hwald, Fabrication of Micro Reaction Cages with Tailored Properties, J. Am. Chem. Soc. , 2001, 123, 5431 – 5436.
W.Tong, H. Song, C. Gao, H. M & A ; ouml ; hwald, Equilibrium Distribution of Permeants in Polyelectrolyte Microcapsules Filled with Negatively Charged Polyelectrolyte: The Influence of Ionic Strength and Solvent Polarity, J. Phys. Chem. B, 2006, 110, 12905 – 12909.
G.B. Sukhorukov, M. Brumen, E. Donath, H. M & A ; ouml ; hwald, Hollow Polyelectrolyte Shells: Exclusion of Polymers and Donnan Equilibrium, J. Phys. Chem. B, 1999, 103, 6434 – 6440.
V.V. Lulevich, I.L. Radtchenko, G.B. Sukhorukov, O.I. Vinogradova, Mechanical Properties of Polyelectrolyte Microcapsules Filled with a Impersonal Polymer, Macromolecules, 2003, 36, 2832 – 2837
G. Sukhorukova, A. Feryb, H. M & A ; ouml ; hwald, Intelligent micro- and nanocapsules, Prog. Polym. Sci. , 2005, 30, 885 – 897.
T.S. Harrison, K.L. Goa, Long-Acting Risperidone: A Review of Its Use in Schizophrenia, CNS Drugs, 2004, 18, 113 – 132.
A.P.R. Johnston, C. Cortez, A.S. Angelatos, F. Caruso, Layer-by-layer engineered capsules and their applications, Current Opinion in Colloid & A ; Interface Science, 2006, 11, 203 – 209.
Z. Foldes-Papp, U. Demel, G.P. Tilz, Laser scanning confocal fluorescence microscopy – an overview, International Immunopharmacology, 2003, 3, 1715 – 1729.
C. Dejugnat, D. Halozan, G.B. Sukhorukov, Defined Picogram Dose Inclusion and Release of Macromolecules utilizing Polyelectrolyte Microcapsules, Macromol. Rapid Comm. , 2005, 26, 961-967.
D. Halozan, U. Riebentanz, M. Brumen, E. Donath, Polyelectrolyte microcapsules and coated CaCO3 atoms as fluorescence activated detectors in flowmetry, Colloids Surf. A: Physicochem. Eng. Aspects, 2009, 342,115 – 121.
I. Estrela-Lopis, S. Leporatti, D. Clemens, E. Donath, Polyelectrolyte multilayer hollow capsules studied by small-angle neutron sprinkling ( SANS ) , Soft Matter, 2009, 5, 214 – 219.
V.N. Paunov, O.J. Cayre, Supraparticles and “ Janus ” Particles Fabricated by Replication of Particle Monolayers at Liquid Surfaces Using a Gel Trapping Technique, Adv. Mater. , 2004, 16, 788 – 791.
A.K.F Dyab, M. Ozmen, M. Ersoz, V.N. Paunov, Fabrication of fresh anisotropic magnetic microparticles, J. Mater. Chem. , 2009, 19, 3475 – 3481.
A. Perro, S. Reculusa, S. Ravaine, E. Bourgeat-Lami, E. Duguet, Design and synthesis of Janus micro- and nanoparticles, J. Mater. Chem. , 2005, 15, 3745 – 3760.
H.A. Jerri, R.A. Dutter, D. Velegol, Fabrication of stable anisotropic microcapsules, Soft Matter, 2009, 5, 827 – 834.
Z. Li, D. Lee, M.F. Rubner, R.E. Cohen, Layer-by-Layer Assembled Janus Microcapsules, Macromolecules 2005, 38, 7876 – 7879.