ntroduction to polymeric nanoparticles, PLGA coreshell particles and micelles

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Introduction to polymeric nanoparticles, PLGA coreshell particles and micelles

Nanopolymers

Polymer nanocomposites (PNC) is a polymer or copolymer having dispersed in its nanoparticles. These may be of different shape (e.g., platelets, fibers, spheroids), but at least one dimension must be in the range of 1 to 50 nm. These PNC's belong to the category of multi-phase systems (MPS, viz. blends, composites, and foams) that consume nearly 95% of plastics production. These systems require controlled mixing/compounding, stabilization of the achieved dispersion, orientation of the dispersed phase, and the compounding strategies for all MPS, including PNC, are similar. Because of the higher surface area of the nano-particles, the interaction with the other particles within the mixture is more and this increases the strength, heat resistance, etc and many factors do change for the mixture.

An example of a nanopolymer is silicon nanospheres which show quite different characteristics; their size is 40 – 100 nm and they are much harder than silicon, their hardness being between that of sapphire and diamond.

Bio-hybrid polymer nanofibers

Many technical applications of biological objects like proteins, viruses or bacteria such as chromatography, optical information technology, sensorics, catalysis and drug delivery require their immobilization. Carbon nanotubes, gold particles and synthetic polymers are used for this purpose. This immobilization has been achieved predominantly by adsorption or by chemical binding and to a lesser extent by incorporating these objects as guests in host matrices.

Applications

The nanofibres, hollow nanofibres, core-shell nanofibres, and nanorods or nanotubes produced have a great potential for a broad range of applications including homogeneous and heterogeneous catalysis, sensorics, filter applications, and optoelectronics.

Tissue engineering

This is mainly concerned with the replacement of tissues which have been destroyed by sickness or accidents or other artificial means. The examples are skin, bone, cartilage, blood vessels and may be even organs. This technique involves providing a scaffold on which cells are added and the scaffold should provide favorable conditions for the growth of the same. Nanofibres have been found to provide very good conditions for the growth of such cells, one of the reasons being that fibrillar structures can be found on many tissues which allow the cells to attach strongly to the fibers and grow along them as shown.

Delivery from compartmented nanotubes

Nano tubes are also used for carrying drugs in general therapy and in tumor therapy in particular. The role of them is to protect the drugs from destruction in blood stream, to control the delivery with a well-defined release kinetics, and in ideal cases, to provide vector-targeting properties or release mechanism by external or internal stimuli.

Rod or tube-like, rather than nearly spherical, nanocarriers may offer additional advantages in terms of drug delivery systems. Such drug carrier particles possess additional choice of the axial ratio, the curvature, and the “all-sweeping” hydrodynamic-related rotation, and they can be modified chemically at the inner surface, the outer surface, and at the end planes in a very selective way. Nanotubes prepared with a responsive polymer attached to the tube opening allow the control of access to and release from the tube. Furthermore, nanotubes can also be prepared showing a gradient in its chemical composition along the length of the tube.

Compartmented drug release systems were prepared based on nanotubes or nanofibres. Nanotubes and nanofibres, for instance, which contained fluorescent albumin with dog-fluorescein isothiocyanate were prepared as a model drug, as well as super paramagnetic nanoparticles composed of iron oxide or nickel ferrite. The presence of the magnetic nanoparticles allowed, first of all, the guiding of the nanotubes to specific locations in the body by external magnetic fields. Super paramagnetic particles are known to display strong interactions with external magnetic fields leading to large saturation magnetizations. In addition, by using periodically varying magnetic fields, the nanoparticles were heated up to provide, thus, a trigger for drug release. The presence of the model drug was established by fluorescence spectroscopy and the same holds for the analysis of the model drug released from the nanotubes.

Immobilization of proteins

Core shell fibers of nano particles with fluid cores and solid shells can be used to entrap biological objects such as proteins, viruses or bacteria in conditions which do not affect their functions. This effect can be used among others for biosensor applications. For example Green Fluorescent Protein is immobilized in nanostructured fibres providing large surface areas and short distances for the analyte to approach the sensor protein.

With respect to using such fibers for sensor applications, the fluorescence of the core shell fibers was found to decay rapidly as the fibers were immersed into a solution containing urea: urea permeates through the wall into the core where it causes denaturation of the GFP. This simple experiment reveals that core-shell fibers are promising objects for preparing biosensors based on biological objects.

Polymer nanostructured fibers, core-shell fibers, hollow fibers, and nanorods and nanotubes provide a platform for a broad range of applications both in material science as well as in life science. Biological objects of different complexity and synthetic objects carrying specific functions can be incorporated into such nanostructured polymer systems while keeping their specific functions vital. Biosensors, tissue engineering, drug delivery, or enzymatic catalysis is just a few of the possible examples. The incorporation of viruses and bacteria all the way up to microorganism should not really pose a problem and the applications coming from such biohybrid systems should be tremendous.

 PLGA coreshell particles

PLGA or poly(lactic-co-glycolic acid) is a copolymer which is used in a host of Food and Drug Administration (FDA) approved therapeutic devices, owing to its biodegradability and biocompatibility. PLGA is synthesized by means of random ring-opening co-polymerization of two different monomers, the cyclic dimers (1,4-dioxane-2,5-diones) of glycolic acid and lactic acid. Common catalysts used in the preparation of this polymer include tin(II) 2-ethylhexanoate, tin(II) alkoxides, or aluminum isopropoxide. During polymerization, successive monomeric units (of glycolic or lactic acid) are linked together in PLGA by ester linkages, thus yielding a linear, aliphatic polyester as a product.

Depending on the ratio of lactide to glycolide used for the polymerization, different forms of PLGA can be obtained: these are usually identified in regard to the monomers' ratio used (e.g. PLGA 75:25 identifies a copolymer whose composition is 75% lactic acid and 25% glycolic acid). All PLGAs are amorphous rather than crystalline and show a glass transition temperature in the range of 40-60 °C. Unlike the homopolymers of lactic acid (polylactide) and glycolic acid (polyglycolide) which show poor solubilities, PLGA can be dissolved by a wide range of common solvents, including chlorinated solvents, tetrahydrofuran, acetone or ethyl acetate.

PLGA degrades by hydrolysis of its ester linkages in the presence of water. It has been shown that the time required for degradation of PLGA is related to the monomers' ratio used in production: the higher the content of glycolide units, the lower the time required for degradation. An exception to this rule is the copolymer with 50:50 monomers' ratio which exhibits the faster degradation (about two months). In addition, polymers that are end-capped with esters (as opposed to the free carboxylic acid) demonstrate longer degradation half-lives.

PLGA has been successful as a biodegradable polymer because it undergoes hydrolysis in the body to produce the original monomers, lactic acid and glycolic acid. These two monomers under normal physiological conditions, are by-products of various metabolic pathways in the body. Since the body effectively deals with the two monomers, there is very minimal systemic toxicity associated with using PLGA for drug delivery or biomaterial applications. Also, the possibility to tailor the polymer degradation time by altering the ratio of the monomers used during synthesis has made PLGA a common choice in the production of a variety of biomedical devices such as: grafts, sutures, implants, prosthetic devices, micro and nanoparticles. It has also been used successfully in delivery Amoxicillin in treating listeriosis (treatment of Listeria monocytogenes infection) As an example, a commercially available drug delivery device using PLGA is Lupron Depot^Ⓡ for the treatment of advanced prostate cancer.

A micelle is an aggregate of surfactant molecules dispersed in a liquid colloid. A typical micelle in aqueous solution forms an aggregate with the hydrophilic "head" regions in contact with surrounding solvent, sequestering the hydrophobic single tail regions in the micelle centre. This phase is caused by the insufficient packing issues of single tailed lipids in a bilayer. The difficulty filling all the volume of the interior of a bilayer, while accommodating the area per head group forced on the molecule by the hydration of the lipid head group leads to the formation of the micelle. This type of micelle is known as a normal phase micelle (oil-in-water micelle). Inverse micelles have the headgroups at the centre with the tails extending out (water-in-oil micelle). Micelles are approximately spherical in shape. Other phases, including shapes such as ellipsoids, cylinders, and bilayers are also possible. The shape and size of a micelle is a function of the molecular geometry of its surfactant molecules and solution conditions such as surfactant concentration, temperature, pH, and ionic strength. The process of forming micellae is known as micellization and forms part of the phase behavior of many lipids according to their polymorphism. This is usually takes place in soaps when hydrophylic occupies the water and hydrophobic catch hold of the dirt in clothes we wash