The pharmaceutical industry has evolved with respect to healthcare to patients according to the needs of the respective generations. Up to a certain extent, it has fulfilled the ever-rising demands but predominantly the pace of the research and the implementations have not been up to the mark.
Probably the reason why certain high profile diseases like cancer, HIV, hormonal imbalances, neurological disorders, cognitive failures, etc, constantly require innovations at various levels.
Now, one of the major aspects in the drug to disorder relationship is the pharmacokinetics; which is a direct correlation of the dose to its pharmacological effect on the intended organ of the body. Therefore, the focus of this particular project has been on the Drug Delivery Dynamics.
The Drug Delivery related research is widely focused on nanotechnology and hence, we need to elaborate on nanoparticles and microparticles.
Nanoparticles are essentially the particles that are below 100nm in size. The wide range of applications pertaining to nanoparticles from biomedical, optical to electronic fields has in turn helped immensely in devising novel techniques as far as drug delivery is concerned.
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The stability of nanoparticles is not desirable as compared to that of a bulk material they are a part of; however, this instability is irrelevant at a nano-scale.
The instability of the nanoparticles may be attributed to 'quantum confinement in semiconductor particles', metal particles that display 'surface Plasmon resonance' and as the name would suggest, the magnetic materials imply 'superparamagnetism'. 'Superparamagnetism' is a concept in which materials such as iron, form permanent magnets. The most relevant aspect about the properties just mentioned, is that they are all size-dependent while maintaining their intrinsic nature.
The properties of the particles vary on two variables; firstly, when the size itself approaches the nano scale and secondly, when the nanoparticles assemble more towards the surface of the material.
However, for bulk materials larger than one micrometre, the percentage of atoms towards the surface is significantly negligible.
The properties of the nanoparticles and the intrinsic nature of the bulk material are interrelated. Although, the bulk material has a predominant influence on the overall behaviour of the nanoparticles, nanoparticles have their own variables that contribute to the variations in their stability with respect to the bulk materials.
To demonstrate the above theory, an example quotes that a copper rod, when bent, brings about the nanoparticles to cluster at about 50 nm scale.
On the other hand, the particles sized less than 50 nm do not comply with the bulk material in terms of the malleability.
Therefore, it is very important to judge whether the variations in properties are desirable or not.
Nanoparticles structures can be roughly classified as per following:
It is important to note that most of the nanoparticles share the following properties, which make them useful for the concerned applications:
Ease of synthesis
The area of interest here has to be Nanomedicine which relates to the use of nanoparticles for drug delivery. The research is ongoing for the extrapolation of the technique for the purpose of molecular nanotechnology (MNT) and nanovaccinology.
As far as biomedical research pertaining to nanoparticles is concerned, the classification should well be application based as follows:
Semi-hydrogel networks of poly(acrylamide) and carbohydrates: antibacterial application
Inorganic nanoparticles for Biotechnology
Platinum-palladium alloy nanoparticles for electrochemical applications
Nanoparticles for Dental Materials
Noble metal nanoparticles/carbon nanotubes nanohybrids
Plasmonic nanoparticles for biomedical applications
Preparation of semisolid drug carriers for topical application based on solid lipid nanoparticles
Lanthanide-doped upconversion nanoparticles for biomedical applications
Applications of nanoparticles by a high gravity method
Synthesis of nanoparticles by microorganisms and their application in enhancing microbiological reaction rates
Forthcoming applications of gold nanoparticles in drug and gene delivery systems
Semi-hydrogel networks of poly(acrylamide) and carbohydrates:
The nanoparticles have been used here for the preparation of semi interpenetrating hydrogel networks (SIHNs) which require a poly(acrylamide) cross-linked base. The polymerization is carried out in a redox-solution by incorporating N,N'-methylenebisacrylamide (MBA), while there is a further incorporation of carbohydrates, namely gum acacia (GA), carboxymethylcelluose (CMC) and starch (SR).
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The outcome of the above incorporations leads to the formation of highly stable silver nanoparticles with the hydrogel networks as the nanoreactors. Since there is a redox reaction involved, an in situ reduction of silver nitrate (AgNO3) with the interference of sodium borohydrate (NaBH4) which is a reducing agent.
The antibacterial activity of the silver nanoparticles has been attributed to the use of the atomic scale functional materials. However, the silver nanoparticles contribute by increasing the number of resistant strains of bacteria to the most potent antibiotics. The key element in the antibacterial activity of the silver nanoparticles is the size, which should ideally be between 1-10nm.
Inorganic nanoparticles for Biotechnology:
The usefulness of the nanoparticles hinges mainly upon two factors:
Large surface area to volume ratio. This in addition to the efficient chemical functionalisation, enables the bonding of the multifunctional cargo payload (for example, a fluorescent moiety, targeting molecules, etc.)
The fact that the nanoparticles offer a larger surface area, means that they can have an access across more tissues that were otherwise not possible to be accessed.
As the name suggests, the magnetic nanoparticles have a magnetic core as an integral component namely magnetite or maghemite. Cobalt and nickel have also been used; but due to their toxic and susceptible to oxygen, the usage is restricted.
The iron oxide magnetic nanoparticles (mNPs) are adopted bearing an idea that the human body is efficient enough in processing excess of iron.
The basic role of targeted drug delivery is fulfilled as the cationic mNPs are able to efficiently enter the cells and remain localised in the endosomes for a sustained period of time.
The transfer of iron across various cellular and tissue levels is the most crucially advantageous aspect of the mNPs; because, the iron that is a component of the endosomes and lysosomes (which is a part of the post-cellular uptake) is converted into elemental iron through metabolism and into oxygen by hydrolytic enzymes, where the iron joins the normal body stores.
Thus, the homeostasis of iron can be regulated by the use of iron oxide nanoparticles, essentially by processing any excess iron present.
The superparamagnetic iron oxide (SPIO) nanoparticles are the components influenced by an external magnetic field; as a contrast, removing the external field eliminates the paramagnetism.
The purpose behind the application of an external magnetic field is that it allows lesser concentration of the particles to produce an equivalent signal feedback.
Magnetic Resonance Imaging:
The use of magnetic nanoparticles in Magnetic Resonance Imaging (MRI) has been one of the highpoints of diagnostics. The nanoparticles being able to enter into cells belonging to the most dense cluster, gives them an ability to present an image that shows distinct contrasts between different types of cells and eventually tissues (the tendency is also attributed to 'large magnetic moment'). Apart from offering a more distinguishable image quality, they offer slower clearance from the target site.
The term in itself suggests a change with respect to temperature. As it is well known, in the case of cancer, the tumour cells are more susceptible to necrosis under the influence of temperature as compared to that with normal cells. Hence, some sort of a medium through which the heat can be transferred across the tumour cells had to be devised. Therefore, a nanoscale heater concept in which the nanoparticles function as the components that reach out at the concerned cells, has been one of the most significant innovations in cancer therapy.
The process is based on the fact that the external electromagnetic field provided to the nanoparticles is converted to heat.
One of the practical implementations of the concept of hyperthermia is the study of the effect of temperature on the uptake of doxorubicin (an anticancer medicine) by human breast cancer cells.
On the basis of a similar principle of the ability of the magnetic nanoparticles being able to reach out at different strata of the cellular organization, mNPs have applications in magnetic drug targeting, magnetic transfection, etc.
Gold nanoparticles (AuNPs), also known as colloidal gold, have been very extensively in use for a century. The most advantageous aspect of these particles could be the varying colours with respect to their varying size; for example, particles below 100nm are red and the larger ones are mostly yellow in colour.
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The gold nanoparticles work on the principle of absorbing the scattering light which leads to excitation of the electrons resulting into oscillations. These oscillations are also known as surface Plasmon. This collectively helps in enhancing the biological imaging.
On similar principles as the mNPs work, gold nanoparticles too have been used as Cell Delivery Vehicles and Biosensors.
They probably differ from the gold nanoparticles by their crystalline structures. They comprise of Cd, Zn, Se, Te, In, O, As, as some of the elements.
Their applications vary from Single Cell Imaging, In Vitro Imaging and Targeted Therapies as similar as that in the magnetic nanoparticles.
They are essentially hollow and porous nanoparticles known as nanotubes, nanoshells and hollow spheres; so that they can be loaded with cargo, and it is observed that it enhances the signal and sensitivity.
The most advantageous properties of the carbon nanotubes are the easier translocation across the cell membrance and relatively low toxicity. The carbon nanotubes can be either single-walled or multi-walled.
Their applications involve relatively high profile implications as compared to some of the other forms of nanoparticles:
Neuronal Tissue Engineering
Figure 2: a substrate patterned with carbon nanotubes is cultured with Neuronal networks (A). Aligned neurites as a result of the patterned growth over a period of 14 days (B).
Imaging and Cancer Treatment.
Imaging and Cancer Treatment
Platinum-palladium alloy nanoparticles for electrochemical applications:
The applicability of the nanoparticles in terms of detecting various other compounds is tested by preparing platinum-palladium alloy nanoparticles/large mesoporous carbon (LMC) nanocomposites (PtxPdy/LMC), where the subscripts X and Y represent the different rations of Pt and Pd.
The introduction of the various proportions of PtxPdy alloy nanoparticles upon the surface of an LMC matrix enable the interaction of the two and brings about peroxide reduction and nitrite oxidation; which otherwise is not possible with depositing Pt on LMC matrix surface. The entire set of Pt1Pd1/LMC nanoparticles modified glassy carbon electrode implies an excellent electrolytic capability, and therefore it has been deemed to be practically useful to detect other compounds.
Gold nanoparticles, as discussed before, are significant enough to be categorized separately; one of the reasons being their environment oriented applications in greener production methods, pollution control and water purification.
Gold nanoparticles are in nature more stable compared to other forms of nanoparticles and may be hence they provide applicability in forming appropriate conditions to make a number of catalysts that includes:
Catalysis of CO oxidation
Catalysis of hydrogenation of unsaturated substrates
Electrochemical Redox catalysis of CO and CH3OH oxidation and O2 reduction
Catalysis by functional thiolate-stabilized gold nanoparticles, etc.
Mercury control and sensing: the advantage of controlling and sensing mercury could well be elaborated if required. For example, mercury is generally toxic in nature and thus responsible for a number of adversities such as Alzheimer's disease and autism. To add to the advantage, gold nanoparticles have been found to act as catalysts for the oxidation of mercury.
Oxidation of CO to CO2.
In technology: applications such as in coating glasses so as to change their overall properties and multicolour optical coding for biological assays
To enhance electroluminescence and quantum efficiency in organic light emitting diodes.
Detection of trace amounts of the analytes to the extent of a few ppm.
Making of advanced dyes and pigments.
Nanoparticles for Dental materials:
As apparent, the use of nanoparticles in dental materials is for the purpose of improving their optical properties. The use of nanoparticles significantly reduces the stress on mechanical strength and the wear resistance is not sacrificed either.
Clinical experience with dental materials:
The use of the nanofill composite Filtek is at the cetre point of the nanoparticles driven restorations. Therefore, it was observed that the use of nanoparticles offers following advantages:
Long-term universal application to restore dentition
Providing excellent anaesthetics, mechanical function and wear resistance
Longevity of the treatment as high as a period of 3 years was observed, with a peculiar property of self-polishing of the treated surface.
Noble metal nanoparticles/carbon nanotubes nanohybrids:
The focus is shifted slightly on the use of novel forms of nanoparticles with the overall applicability not being too different from that elaborated earlier.
Some of the applications like:
Hybridization of cinnamaldehyde in heterogenous catalysis
Suzuki coupling, selective hydrogenation, CO oxidation, NH3 synthesis and hydrodehalogenation are some of the other examples of heterogenous catalysis.
Figure 3: scheme of carbon nanoparticles for Heck coupling reaction
Similarly, the novel nanoparticles can be used in:
Fuel cells and electrocatalysis
Plasmonic nanoparticles for biomedical applications:
Nanoparticles is one of the emerging technologies in which the research is focused on the fabrication and optical characterization of noble metal nanoparticles varying in aspects like size, shape, structure and tunable Plasmon resonances over VIS-NIR spectral band.
Preparation of semisolid drug carriers for topical application based on solid lipid nanoparticles:
The topical drug delivery is one of the most prevalent and profitable area of pharmaceutical industry, because of the sheer scope in terms of treatment of minor ailments/cosmetic substitutions with irreplaceable remedies.
Therefore, aqueous dispersions of solid lipid nanoparticles (SLN) are a mode of focus here. The manufacturing of a topical semisolid preparation is a complicated process as it involves the incorporation of the solid-liquid-semisolid phases with use of heavy and time-consuming machinery.
However, the use of the nanoparticles potentially reduces the number of steps to ONE which is especially important because it provides more stability to the end product while offering commercial benefits. The equipment used for the production includes a high-pressure homogenizer.
Lanthanide-doped upconversion nanoparticles for biomedical applications:
Similar to the applications pointed out earlier, these nanoparticles deliver following contributions:
MRI and drug delivery
However, the mention of this type of nanoparticles comes with certain advantages:
Enhanced tissue penetration depths via near-infrared excitation
Photocleaching, photoblinking, photochemical degradation can be avoided
DNA/RNA remain intact without getting photo-damaged at lower excitation light energy
Higher detection sensitivity
Applications of nanoparticles by a high gravity method:
Process that involve a role of the nanomaterials, namely, synthesis, polymerization, special chemicals production, reactive absorption, etc are subjected to micromixing which is essentially a mass transfer.
The device used was the Rotation Packed Bed (RPB, or "HIGEE" device) and a unique and intense micromixing was achieved. This was a trigger point for the use of RPB as a fabricator of nanoparticles.
The high gravity method has been designed for the synthesisof nanoparticles such as inorganic and organic with the implementation of gas-liquid, liquid-liquid and gas-liquid-solid multiphase reactions.
Example: inorganic nanoparticles like nanosized CaCO3, TiO2, SiO2, ZnO, Al2O3, ZnS, BaTiO3, etc.
Synthesis of nanoparticles by microorganisms and their application in enhancing microbiological reaction rates:
This particular process works as a complementary procedure, in which, the nanoparticles are first synthesized with the help of micro-organisms such as bacteria, fungi, actinomycetes and yeast and then their effect on the microbial processes is taken into consideration.
The nanoparticles are most widely used for the purposes of reductants and/or catalysts in the field of chemistry because mainly of the two highpoints:
Highly specific surface areas
Although the number of studies conducted on the effect of nanoparticles on the reaction rates is limited, there are some examples which point out the significance of the technique. For example, the formation of the nanosized palladium particles formed on the cell wall or inside the periplasmic region of a bacterium named Shewanella aneidensis brought about a reduction of the dehalogenate polychlorinated biphenyl (PCB).
Forthcoming applications of gold nanoparticles in drug and gene delivery systems:
This particular section expands the applicability of the nanoparticles from drug delivery to gene delivery. The importance of reemphasizing the importance of the gold nanoparticles is because they can be modified to optimum parameters to be suitable for a more intricate level of biomedical delivery system.
As mentioned in a previous section, features such as surface Plasmon resonance, controlled interaction with the thiol groups and most importantly, the non-toxic nature contribute towards devising appropriate dynamics for the gold particles to be efficient.
The nanoparticles intervened drugs present certain improvements in their overall properties which include:
Improvement in solubility
In vivo stability
Similarly, the gold nanoparticles can also be used to carry nucleic acids; hence, the purpose of gene therapy can be focused on. The details into how the entire process is carried out, is irrelevant in this context.
Microparticles essentially differ from nanoparticles in terms of the particle size, however, the difference reflects on to their overall applications when compared to that of the nanoparticles. But the most prevalent attributes between the two classes do not change beyond a certain level.
The size range of the microparticles is between 0.1 to 100 micrometres.
The most commonly found microparticles are sourced from ceramics, glass, polymers and metals.
More natural forms of microparticles include pollen, sand, dust, flour and powdered sugar.
Similar to the principle on which the nanoparticles have been proven to be advantageous, microparticles also have a large surface-to-volume ratio at the macroscale. However, this level of dynamics can be challenging to handle at the industrial level, for example, metal microparticles can be explosive in air.
Application of sulphur microparticles for solid-phase extraction of polycyclic aromatic hydrocarbons from sea water and wastewater samples
Boc-L-tryptophan imprinted polymeric microparticles for bioanalytical applications
Characterization and application to entrapment into biodegradable microspheres
Composite polymer-Fe3O4 microparticles for biomedical applications, produced by Supercritical Assisted Atomization
Design and characterization of bi-soft segmented polyurethane microparticles for biomedical application
Microparticles with GOx for biosensor applications
Preparation and characterization of starch-poly-Ô‘-caprolactone microparticles incorporating bioactive agents for drug delivery and tissue engineering applications
Production and characterization of chitosan microparticles
Tissue engineering applications
Topical applications related to acyclovir-loaded microparticles
Application of sulphur microparticles for solid-phase extraction of polycyclic aromatic hydrocarbons from sea water and wastewater samples:
As compared to the nanoparticles, the microparticles possess a larger size and hence a lesser size to surface ration. Therefore, microparticles can be practically useful as adsorbents.
In this case, the sulphur microparticles function as efficient adsorbents and bring about solid-phase extraction (SPE) and as a consequence determine the trace amounts of 10 polycyclic aromatic hydrocarbons (PAHs). The magnitude of this application is enormous when it is considered that the extraction is carried out from the sea water and wastewater using various separation techniques that mainly include the HPLC (High Profile Liquid Chromatography) coupled with UV detector (ultraviolet detector).
Cell/Tissue Engineering Applications:
In this case, an engineered breed of alginate-based microparticles is produced in order to be applicable for their use in turn as cell/tissue engineering media.
The alginate-based microparticles are formed of an extracellular matrix and neonatal porcine Sertoli cells (SCs). This technique is unique in a way that the source of the matrix was a powder form of isolated and purified urinary bladder matrix (UBM).
The use of the UBM implied that it did not alter the core morphological integrity and the overall dimensional characteristics of the microparticles.
The crux of the above procedure is their applicability in the cell/tissue engineering process. The alginate microparticles were used for the SC encapsulation as an immunoprotective barrier for transplant purposes; on the other hand, the co-entrapped UBM functioned to promote the cell viability and function.
As mentioned before, this technique is very novel in its own way, because it works in a complementary way by increasing the functional life-span of the entrapped cells for cell/tissue engineering applications.
Deign and characteristics of bi-soft segmented polyurethane microparticles:
The modifications at various levels are concentrated towards developing biomedical applications. In this case, the Bi-soft segmented poly(ester urethane urea) microparticles have been prepared and then have been characterized.
Although the biomedical applications offered don't vary radically, it is worth noting the method of preparation of the microparticles so as to correlate with the properties of the same if required.
Two parallel formulations were prepared:
Using poly(propylene oxide)-based tri-isocyanated terminated pre-polymer (TI).
Soft segmented added for the purpose of incorporating poly(Ô‘-caprolactone)diol (PCL).
The method of analysis used to study the polymeric structure was infrared spectroscopy. The analysis determined the degree of phase separation between the two formulations, in which it was found that the TDI-microparticles show a higher extent of phase separation, and TI-microparticles on the other hand show higher rate of hydrolytic degradation, and therefore, consequently lower toxic effect against the macrophages.
These new formulations can be categorized as the non-biodegradable biomedical systems.
Powder technology: Supercritical Assisted Atomization:
The applications remain generalized to biomedical applications here as well. However, the efficiency improvement is what has been the aim in devising the novel methods of preparation of microparticles and their relevant advantages over their counterparts.
In this case, the Supercritical Assisted Atomization (SAA) is used as an efficient supercritical fluid (SCF) micronization technique.
The most distinct feature of this technique is that it adopts the production of the composite microparticles, which literally mean a composition of more than one component. Therefore, multiple components can be processed.
SAA can be used in the formation of magnetite nanoparticles, derived from the suspensions of nanoparticles in polymer-solvent solutions.
Dextran and chetosan; both glucose derivatives, dextran is a branched glucan (polysaccharide formed by the chain of glucose) and chitosan can be termed as a linear polysaccharide composed of random glucosamine (deacylated unit) and N-acetyl-D-glucosamine (acetylated); have been used as dispersing matrix.
The biocompatibility can be gained by encapsulating the polymer coating, also the particles are physically more stable because they are protected by a steric barrier so as to prevent agglomeration and also avoid opsonisation.
The efficiency of the dispersion was analysed by using
Surface Electron Microscopy (SEM)
Energy Dispersion X-ray (EDX)
Now these techniques actually are able to determine the overall morphology, particle size distribution, nanostructure and the concentration of the loaded nanoparticles/microparticles in the polymeric matrix.
Targeted transfollicular delivery of artocarpin extract with the help of an organism Artocarpus incises by the use of microparticles:
A heartwood named Artocarpus incises is the source of Artocarpus (Ar), which is a plant bearing edible fruits, is pharmacologically important that reduces the 5 alpha inhibitory effect. The biggest problem for the potential therapy by Ar was the lack of appropriate drug delivery mechanism.
Therefore, the employment of alginate/chitosan (ACS) microparticles for targeted transfollicular delivery with a suitable particle size between 2 and 6 micrometres was an area of research. Ionotropic gelation technique, which is a coacervation-phase separation technique that involves:
Formation of 3 immiscible chemical phases
Deposition of coating
Rigidization of coating
This brief explanation focuses back on the drug delivery related applicability of the microparticles, which can be explored further in case of a requirement.
Bioanalytical applications: Boc-L-tryptophan imprinted polymeric microparticles:
There is a concept named molecularly imprinted polymers, which is essentially, as the name suggests, employs molecular imprinting technique that is useful in forming cavities in a polymer matrix with affinity to a desired template molecule in microparticles.
Now these microparticles with efficient separation that is chromatographic characteristics were synthesized with the use of the suspension polymerization process in one single preparation step. There are a lot of potential variables during the processing that affect the end product, those are, porogen concentration, polymerization temperature, functional monomer types and their concentrations and the cross-linker used. Now these variables mainly affect the particle size distribution and the particle morphology.
The fact that this technique uses templates in some way, it implies that its applications can be targeted to the bioanalytical separation of peptides and proteins which are the components of a chain formation as far as amino acids in general are concerned, and hence they are the building units of a chain forming larger biomolecules.
Biosensor Applications: polypyrrole/polyacrylamide microparticles:
The sulfonate dopant anion, which is a doping agent which is essentially a trace impurity element that alters the electrical and optical properties when inserted into a substance.
This dopant anion is used in the synthesis of polypyrrole. To make a controlled release drug form, polypyrrole was incorporated into the water phase of the water in oil (W/O) concentrated emulsion. This combined with the varying amounts of the acrylamide monomer and the crosslinker bisacrylamide.
Now the water-dispersed portion is capable of forming the microparticles that size with an average value of 4.5 micrometres, as mentioned above, polypyrrole is entrapped.
Now the conductivity varies against the proportions of polypyrrole vs polyacrylamide in the water phase. The aim is to maintain it within the range of semiconductor materials' conductivity.
GOx (glucose oxide) was the next focus, it was immobilized in the microparticles so as to maintain its stability and efficacy by incorporating the enzyme into the water phase (same phase as mentioned above) and then the next major step was the polymerisation.
The entire incorporated phase was used as a biological component of an amperometric glucose sensor that is sensitive to glucose under the aerobic and anaerobic conditions.
Now, apart from all the revolving techniques used, the above protocol emphasizes more on the importance of the immobilization technique and the relevant possible applicability of the semi-conducting microparticles.
Characterization and entrapment into biodegradable microspheres:
Gelatin microparticles are the main components to be entrapped into the biodegradable microspheres in this case.
Microspheres are essentially spherical microparticles with details that are not totally relevant in the context.
Now the gelatin microparticles were prepared by carrying out something known as co-lypophilization with the poly(ethylene glycol) (PEG), which works as a protein micronization adjuvant.
Lyophilisation is a process in which the substance is subject to dehydration so as to preserve it.
The intricate details of the entire process can be studied as per the requirements; however, all that is important to note is that this technique is useful in studying as well as developing various drug delivery systems.
The following diagram illustrates in brief, how the formation of gelatin microparticles is carried out:
Figure 4: Formation of Gelatin microparticles.
Courtesy: Takahiro Morita, et al.
Topical application of acyclovir-loaded microparticles:
Acyclovir is basically a guanosine analogue antiviral drug.
Therefore, the drug designing in this context revolves around acyclovir; and hence the aim was set to be the increase in the level of acyclovir (ACV) in the basal epidermis, which is the target site for the virus causing the Herpes simplex infections.
Now, by using the microparticles as carriers, a co-solubilisation of the ACV with Poly(D,L-lactic-co-glycolic acid) was done with the use of a solvent evaporation technique.
Now, to determine the concentration of the ACV into the skin was determined by slicing out the porcine skin and the layer of the skin tested was the basal epidermis.
As an arbitrary conclusion, it was found that the drug retention was significantly increased by the use of microparticles when the transdermal drug delivery was taken into consideration.
Use of chitosan microparticles containing papain:
On similar lines to ACV as discussed above, the chiotosan microparticles were tested for their capability as the controlled drug delivery carriers by using crosslinking agents and papain.
Papain is (a cysteine protease enzyme) sorption; along with chitosan was crosslinked with sodium tripolyphosphate (TPP) 10% (w/v) solution or glutaraldehyde (GLU) 0.75% (w/w).
The characterization of the microparticles was carried out with the help of the FTIR (Fourier transformed infrared spectroscopy) for detecting chemical modifications, the morphology was tested by using the SEM (scanning electron microscopy) and DSC (Differential scanning calorimetry).
The papain and TPP were found to lower the stability of the chitosan matrix, and probably as a result, the drug delivery was possible through the matrix.
Therefore, it was concluded that this technique was potentially useful for the controlled drug delivery of papain with potential biomedical applications.
THE CLAY MINERALS:
The clay minerals are a class of layered silicates that are present in abundance as the fine-grained fraction of soils and sediments. The layered structures give them a nomenclature as PHYLLOSILICATES.
The clays share advantages as well as disadvantages for being majorly crystalline in nature.
The particle size of the clay minerals is most frequently below 2 micrometres. Being crystalline in nature, they possess an equivalent spherical diameter (e.s.d.).
Therefore, clays can be correlated to the properties of the microparticles in general, yet there needs to be a detailed analysis in deciding in which aspects do they have similar attributes as those of the microparticles in general.
The reason behind the analysis is required is because, not all clay minerals are below 2 micrometres and not all possess a crystalline structure.
It is necessary to clarify the difference between the term 'clay mineral' and 'clay'. 'clay' pertains to naturally occurring material of fine-grained texture that has the tendency to become plastic when subject to a liquid and consequently has the tendency to harden when dried or fired.
On the other hand, the 'clay minerals' are essentially hydrated phyllosilicates and minerals impart plasticity to clay and then undergo hardening upon drying.
'Clay minerals' can be synthetic unlike the clays which are strictly natural.
The fine-grained nature of clay minerals demands various methods of analysis that include:
Chemical and thermal analyses together with electron microscopy
Now for more detailed and elaborate analyses, the above mentioned techniques have to be complemented with the following techniques:
Fourier transform infrared (FTIR)
Mossbauer, numclear magnetic resonance (NMR)
X-ray photoelectron spectroscopies
However, these techniques can prove to be insufficient when there are certain 'impurities' present that essentially change the basic structural dynamics of clay minerals. These impurities include carbonates, quartz and iron/aluminium hydr(oxides). These impurities are either very discrete in nature or they are surface adsorbed. Therefore, techniques such as X-ray diffractometry (XRD) are not sufficient.
THE SALIENT DYNAMICS OF THE STRUCTURE OF CLAY MINERALS BASED ON SUB-CLASSES:
The phyllosilicates are formed by multilayered components which comprise an alumina-silicate layer comprising a silica tetrahedral sheet and alumina octahedral sheet.
These components are joined together in varying proportions and these proportions actually decide the class of the clay mineral.
The tetrahedron component places the Si4+ cation at the central region of the sheet which is coordinated to four oxygens.
The octahedron has Al3+ at the centre or a Mg2+ at the centre and either of the two coordinated to six hydroxyls.
The structures are geometrically specific, as in, the tetrahedral sheet is formed when the individual tetrahedral are interlinked at three corners each.
This alignment makes the oxygen arrange in a coplanar manner, which forms an overall visually hexagonal structure and a ditriangular structure in reality, while the apical (denoting an apex) oxygens point in the same direction.
On the other hand, the octahedral in the octahedral sheet are linked through sharing edges. When Al3+ acts as a cation, the electrical neutrality is maintained by aligning only two of every three octahedral sites being occupied. The resultant structure as found for example in mineral gibbsite is known as dioctahedral.
On parallel parameters, the Mg2+ induces all three octahedral positions to close in together in order to form bonds which results in the formation of 'trioctahedral'.
The following diagram should give a pictorial presentation of the structures:
Figure 4: "Bottom: (A) a silica tetrahedron in which the central silicon is coordinated to four oxygens (B) a tetrahedral sheet formed by linking silica tetrahedral through corner-sharing. Top (A): an alumina octahedron in which the central aluminium ion is coordinated to six hydroxyls; (B) an aluminium octahedral sheet formed by linking octahedral through edge-sharing" the bigger circles represent Oxygens and the smaller ones represent Silicons. COURTESY: Grim et al, 1968.
The tetrahedral (T) sheet and the octahedral (O) sheet when condensed together, form a 1:1 (T-O) layer structure.
Figure 5: "schematic representation of a silica tetrahedral sheet condensing with an alumina octahedral sheet to form a 1:1-type layer structure. The mode of condensation between the two sheets is indicated by the solid rectangles" COURTESY: B.K.G Theng, et al.
In this case further, the projection of the tips of the tetrahedral sheet occurs into a hydroxyl plane of the octahedral sheet, which replaces two-thirds of the hydroxyl ions as what happens in kaolinite.
Figure 6: (the editing of the text within the diagram was restricted, henceforth the legends are detailed as follows:
Bi-layered structure in which the top portion is the upper surface and the bottom portion is the lower surface.
The circles presented on the left hand side represent:
Aluminium, silicon, oxygen, hydroxyl and water from top to bottom.
The diagram represents "the structure of kaolinite, viewed along the a-axis , showing the superposition of adjacent 1:1-type layers within a particle. The outer hydroxyls are denoted by A and B (both situated along the upper surface). The inner-surface hydroxyls by C and the inner hydroxyl by D (both situated along the lower surface). The basal or d(001) spacing of approx 7 Armstrong units is equal to the layer thickness. The unit cell dimension is indicated by the broken rectangle. CREDITS: modified after Dixon, et al, 1989.