Title of Invention

A PROCESS FOR THE PREPARATION OF POLYMER COATED NANOPARTICLE

Abstract

The invention provides process for the preparation of nanoparticle-polymer complex, as sustain releasing agent for oral care product. The invention demonstrates conditions for the layer-by-layer build-up of polymer multilayers on nanoparticles of size 5-50 nm in diameter. Polymer multilayers have been built using the following components: 1) a core of inorganic compound like silica, titania and/or clay; 2) a hydrophobic shell around the core of polyanion and polycation materials; and 3) the outer layer covering the shell of polyanion having affinity to the enamel of tooth. Then loading the nanoparticles formed as above with active agents like antibacterial and/or flavour compounds. The active agents getting localised in the hydrophobic shell of the nanoparticles for sustained release of the agents, and the aqueous solutions of coated particles being transparent and colourless.

Full Text

Field of the invention The present invention relates to a process for the preparation of nanoparticle-polymer complex as sustained release agents for oral care products. More particularly, the present invention relates to a process for the layer-by-layer build-up of polymer multilayers on nanoparticles of size 5-100 nm in diameter. Background of the invention Layer-by-Layer Assembly of Polyelectrolytes on Surfaces: The layer-by-layer technique is a facile method to produce precisely controlled polymer multilayers on surfaces. This method can be used to coat either flat substrates or particle surfaces. The LbL coating protocol works as follows: first the charged surface to be coated is exposed to a solution of polyelectrolyte of opposite charge relative to the surface. For example, a negatively charged surface is exposed to a polycation solution. The polymer is driven to the surface due to electrostatic attraction and adsorbs on the surface making strong multi-point contact. The long-chain nature of the polyelectrolyte chain results in charge over-compensation on adsorption - thus, the surface in our example now acquires a positive charge after adsorption of the polycation. The excess polycation is then removed (by rinsing in the case of flat substrates; or by centrifugation and washing when particles are coated), and the surface is exposed to a solution of oppositely charged polyelectrolyte (viz. a polyanion solution in the example). This leads to adsorption of the polyanion and a charge reversal to give a negatively charged surface. The excess polyanion is removed and this process is repeated to build up multiple layers of polymer. Typically, each polymer layer is about 1 to 2 nm in thickness and has a mass of around 1 mg.m"2. The LbL process has been described in reviews by Decher (Decher, G. Science 1997, 277, 1232) and by Caruso (Caruso, F. Adv. Mater 2001, 13, 11.). Caruso (Caruso, F, Caruso, R. A., Moehwald, H. Science 1998, 282, 1111.) has also described how coated nanoparticles can be used to prepare shells by removal of the nanoparticle subsequent to LbL coating. One current limitation of this technique is the cumbersome purification step after coating each layer wherein the non-adsorbed polyelectrolyte needs to be removed. If free polyelectrolytes in solution are not removed, then they will complex with the oppositely charged polyelectrolyte added in the next step, leading to precipitation and gelation. As common purification techniques for particles (such as centrifugation) cannot readily be applied to nanoparticles (especially low density nanoparticles such as those prepared from silica), the extension of this technique to nanoparticulate colloids is difficult. Objectives of the invention The main object of the present invention is to provide a process for the preparation of nanoparticle-polymer complex, as agents for sustained release in oral care products. Yet another object of the present invention is to provide a process for the preparation of nanoparticle-polymer complex, wherein the said multi layered polymer coated nanoparticles can be used for the loading of actives such as cinnamaldehyde, cetyl-pyridinium chloride or tin fluoride for making formulations for oral rinses or toothpaste. Still another object of the present invention is to provide a process for the preparation of multi layered polymer coated nanoparticles in aqueous solution. Still another object of the present invention is to provide a transparent and colourless aqueous solution of multi layered polymer coated nanoparticles. Summary of the invention Accordingly the present invention provides a process for the preparation of nanoparticle-polymer complex, as agents for sustained release in oral care products and the said process comprising the steps of: a) preparing an aqueous dispersion of nanoparticles of amorphous silica, titania or synthetic organohectorite (LAPONITE) particles, under stirring, b) adding aqueous solution of polycation of optimized concentration, containing sodium chloride to the above said dispersion of nanoparticles and stirring the resultant solution mixture for a period of 1-2 hrs to obtain the polycation coated nanoparticles in the solution mixture, c) adding an aqueous solution of polyanion of optimized concentration containing sodium chloride to the above solution mixture obtained in step (b) and further stirring the resultant solution mixture for a period of 1-2 hrs to obtain the desired bilayer polymer coated nanoparticles, d) further repeating the above said steps (b) and (c) to obtain the multi layer polymer coated nanoparticles, e) stirring the above said resultant multi layer polymer coated nanoparticles with active agent to obtain the desired active agent loaded -polymer coated nanoparticles to obtain the desired formulations for oral rinses or toothpaste. In yet another embodiment the size of the nanoparticles used in step (a) is in the range of 5-100nm. In yet another embodiment the polyacation used in step (b) is selected from the group consisting of polyethyleneimine (PEI), polyallylamine hydrochloride and polydiallyldimethylammonium chloride. In yet another embodiment the polycation coated nanoparticles obtained are positively charged particles. In yet another embodiment the polyanion used in step (c) is selected from the group consisting of polystyrene sulfonate (PSS), polyacrylic acid-co-maleic acid (PAAMA), polyacrylic acid (PAA), polyglycolic acid (PGA) and copolymer of polyacrylic acid and polyglycolic acid. In yet another embodiment the bilayer and multi layered polymer coated nanoparticles obtained in steps (c) & (d) are negatively charged particles. In yet another embodiment the bilayer and multi layered polymer coated nanoparticles obtained in steps (c) & (d) have exposed carboxyl/sulfonyl groups at the surface. In yet another embodiment the active agent used in step (d) is selected from the group consisting of cinnamaldehyde, cetyl-pyridinium chloride and tin fluoride. In still another embodiment the aqueous solution of multi layer polymer coated nanoparticles obtained in step (d) is transparent and colourless. Brief description of the drawings Figure 1A: UV-Vis spectra of quartz slides after absorption of 1, 2 -7 layers of PSS. The inset shows the increase in absorbance at 230 nm with layer number. The lines joining the points are simply meant as a guide to the eye. Figure 1B: ATR-FTIR on 10 layers of PEI-PAAMA on a silicon wafer. Figure 2: UV-Vis data that shows the decrease in cinnamaldehyde loading from a 10-bilayer PEI-PAAMA coated quartz slide when it is rinsed with water. The inset shows the absorbance values at 300 nm plotted as a function of the rinsing time. The lines connecting the data points are simply meant as a guide to the eye. Figure 3A: TEM of Laponite (top left) showing a nanoparticle with a characteristic dimension of around 25-30 nm, Ludox (top right) showing particles with a typical dimension around 20-30 nm. Images of the coated Laponite (bottom left, coated with PEI-PAAMA)2) and Ludox (bottom right, coated with PEI-PAAMA)3) are unable to resolve the polyelectrolyte. Figure 3B: AFM images of bare mica (left), mica with a dried solution of Ludox (middle) and with (PEI-PAAMA)5 coated Ludox (right). The image on the extreme right shows the false color scale bar used to plot these images. Figure 4: Photographs of a solution of an aqueous dispersion of Ludox-(PEI-PAAMA)5 (right) and of the same solution agitated with cinnamaldehyde (left). The solution stays turbid for over a day. Detail description of the invention Polymer multilayers have been built using the following components: 1) a core of inorganic compound like silica, titania and/or clay; 2) a hydrophobic shell around the core of polyanion and polycation materials; and 3) the outer layer covering the shell of polyanion having affinity to the enamel of tooth. Then loading the nanoparticles formed as above with active agents like antibacterial and/or flavour compounds. The active agents getting localised in the hydrophobic shell of the nanoparticles for sustained release of the agents, and the aqueous solutions of coated particles being transparent and colourless. We synthesize nanoparticle-polyelectrolyte complexes as vehicles for sustained delivery of antibacterials and/or other functional compounds such as flavor agents etc. The method of preparation and the envisaged structure and mechanism of action are described here (see Table 1). We start with aqueous dispersions of charged nanoparticles such as plate-like particles of LAPONITE (a synthetic hectorite comprising of plates that are typically 30nm in diameter and 1nm thick, and that has a negative charge on the surface that are compensated by sodium counterions) or amorphous silica particles (for example, LUDOX or BINDZIL, that are formed by condensation and are available in various sizes such as around 7nm, 15nm, 20nm, etc. These particles bear surface charge due to the presence of ionizable groups). LAPONITE is a rheology-modifier that gels when dispersed in water and is used in oral care applications such as toothpaste. The negatively charged nanoparticles are treated with a solution of a polycation, for example, polyethyleneimine (PEI). The PEI sticks to the surface of the nanoparticle forming a monomolecular coat layer. The deposition of PEI is a function of the ionic strength of the solution - at low ionic strength, the PEI is in an extended conformation while at high ionic strength, the molecules are coiled up. Thus, the ionic strength of the PEL solution controls the process of adsorption and the conformation in which PEI is adsorbed. The polymeric nature of the PEI leads to charge overcompensation at the surface and the PEI coated nanoparticle is now positively charged. The PEI coated nanoparticle is then exposed to a polycarboxylic acid, such as polyacrylic acid (PAA) or polyglycolic acid (PGA) copolymers containing PAA or PGA. The polyacids dissociate in solution and electrostatic interactions between the positively charged PEI coated nanoparticle and the dissociated carboxyl groups drives the coating of the PEI-nanoparticle with the polyacid. In a manner analogous to the PEI coating, the polyacid-PEI-nanoparticle complex now has dangling carboxyl groups and is negatively charged. Also, the deposition of the polyacid and the conformation of the adsorbed polyacid can be tuned via the ionic strength of the solution. Thus, we now have a nanoparticle coated with a two-polymer layer (PEI/polyacid) and that exposes carboxyl groups at the surface. This "layer-by-layer" process can be repeated to produce nanoparticles with as many polymer layers as required. Nanoparticle-polymer complexes are easily dispersible in water and form a clear solution. Their concentrations can be tuned to have a viscosity that is roughly water-like or they can be induced to form gels by inducing aggregation of these nanoparticle complexes, or by changing the amount of polyanion/cation added during synthesis or by changing the ionic strength. Therefore, formulations with a wide range of viscosities can be prepared. Advantages of our approach over conventional layer-by-layer assembly: A typical layer-by-layer scheme involves using excess polyanion and polycation in the coating steps, followed by separation of the excess polymer from the particle-polymer complexes. The process of separation is cumbersome, and for coating nano¬particles, the separation of the nanoparticle is very difficult (if not impossible) using conventional techniques such as centrifugation. To get around this, we use controlled quantities of the polyanions and polycations (calculated based on the surface area and surface charge of the nanoparticles and by estimating a coating thickness, and by extensive subsequent experimental optimization). The details of this procedture are as follows: It is known from previous studies that each layer of polyelectrolyte coated on a flat substrate or a colloid from a salt-containing solution has a coverage of 1 mg.m-2. The particle surface area for a given colloidal dispersion can be easily estimated based on the known average geometrical dimensions of the colloidal particle and the particle concentration in dispersion. Therefore, the amount of polyelectrolyte in the coating solution can be estimated as a product of the coverage (1 mg.m-2) times the total surface area of particles in the dispersion. However, in our work, we determined that using polyelectrolyte solutions with this exact amount of polyelectroyte led to particle aggregation and visible turbidity after one set of polyanion/polycation additions. Polyelectrolyte concentrations lower than this value also led to aggregation and turbidity. By extensive experimentation and careful optimization, we have determined that addition of polyelectrolyte solutions containing between 5 and 10 times the product of coverage and total surface area of particles, leads to clear solutions of multilayer polyelectrolyte coated particles, for up to at least 10 polyelectrolyte bi-layers (polyanion/polycation). Therefore, our optimized procedure for multilayer preparation eliminates costly and complicated separation via centrifugation and our synthesis involves only an easy sequential addition of polyanion and polycation solutions. Further, layer-by-layer assembly techniques in the literature have not reported the coating of "light" (viz. low density) nanoparticles of such small dimensions by multiple layers of polyelectrolytes (coating of gold nanoparticles has been reported, and uses centrifugation for purification). The coated nanoparticle complexes have a polycarboxylic acid as the outermost layer. Therefore, they are expected to adhere strongly to the enamel surface. The presence of multiple-point binding to the enamel by the multiplicity of carboxyl groups on the complex should lead to retention of the complex on the enamel surface for an extended period. This might be tunable using the ionic strength that controls the conformation of the polyacid on the nanoparticle complex surface. Loading of CPC and/or flavor compounds: The nanoparticle-polymer complex presents a large number of carboxyl groups on the surface. A fraction of these groups may be complexed with CPC, and thus the complex can be used to deliver CPC to the enamel surface. CPC is a surfactant-like molecule and has a hydrophobic tail. It is possible that CPC can associate with the complex, not by electrostatic interaction of the quaternary ammonium head group of the CPC with the carboxyl groups, but by hydrophobic interactions of the CPC tail with the multilayer. Similarly, other flavor compounds can also be loaded in the multilayers. For example, flavor oils such as cinnamaldehyde, eugenol or menthol derivatives can be agitated with aqueous solutions of the nanoparticle-complexes to transfer some of the flavor molecules to the hydrophobic inside of the multilayers. These are general strategies for loading the nanoparticle complexes with a variety of agents that can then be retained at the enamel surface due to the adhesion of the loaded complex via the surface carboxyl groups. Thus, in our approach, we use the polymer coating layers as reservoirs for localization of active compounds, as well as anchor the coated particles to the substrate using the charge present on the outer layer that can be varied from positive to negative. Since the particles that we coat are nanometer-sized, we have a large surface area and therefore a significant polymeric reservoir for localization of active compounds. Polyethyleneimine (PEI), Na salt of polystyrene sulfonate (PSS), Na salt of polyacrylic acid-co-maleic acid (PAAMA) and LUDOX silicate nanoparticles were obtained from Aldrich and used as received. PEI had a molecular weight of 75000 g/mol and was received as a 50% solution in water (Aldrich cat. no. 18197-8); PAAMA had a molecular weight of 70000 g/mol (Aldrich cat. no. 416088); PSS had a molecular weight of 75000 g/mol; LUDOX particles with a mean diameter of around 20 nm and sodium counterions on the surface (Aldrich cat. no. 42077-8). Cetyl pyridinium chloride was obtained from Sigma (Cat. no. C-9002) and used as received. Cinnamaldehyde was obtained from S.D. Fine Chemicals and used as received. The water used in all our experiments is distilled deionized water (resistivity = 18.2 Mohm.cm) from a Millipore MilliQ system. LAPONITE was obtained from Southern Clay. LAPONITE is a synthetic organohectorite that contains silicon and magnesium in a clay-like framework. A small degree of isomorphous substitution of the magnesium by sodium gives LAPONITE an excess negative charge of around 0.55 meq/gram of clay. These are satisfied by counterions of sodium that dissociate in aqueous media. LAPONITE are plate-like, with a thickness of around 1nm and an average plate diameter of 30nm. We estimate that there are between 1017 to 1018 plates per gram of clay and that there are roughly on the order of 1000 negative charges present per plate. The following examples are given by the way of illustration and therefore should not be construed to limit the scope of the invention In this section, we first present our results on flat substrates showing LbL build-up of polystyrene sulfonate and PEI; and PAAMA and PEI using FTIR and UV-Vis. We then show results for the retention of cinnamaldehyde in these multilayers. We then detail the procedure for coating the nanoparticles and finally show some data that indicates that these particles in aqueous solution take up cinnamaldehyde. Examplel A solution of LUDOX is prepared by adding 250mg of a 40% (by weight) stock LUDOX solution to 0.95ml of distilled deionized water. This solution is stirred for an extended time (4 hours) so as to completely disperse the LUDOX and to prepare a 0.1 mg/ml solution of LUDOX in water. To this, we add 1ml of PEI solution (at a concentration of 1 mg/ml and, containing 1mM added sodium chloride). The amount of polycation in solution (1mg) is a ten-fold excess over the estimated surface coverage of the particles (0.1 mg). We arrived at this concentration after extensive optimization so that multiple coating steps do not lead to particle aggregation and therefore turbidity of the solution. This mixture is stirred for an hour. To this is added 1ml of a PAAMA solution (at a similarly optimized concentration of 1 mg/ml and, containing 1mM added sodium chloride). This mixture is stirred for an hour. This creates a solution of (PEI-PAAMA) bilayer coated LUDOX particles. We repeat the alternate addition of PEI and PAAMA solutions nine times further to build ten bilayers on the LUDOX. The 10 bilayer-coated LUDOX particles are then stirred with 0.1 ml of an active agent like cinnamaldehyde. The cinnamaldehyde-loaded coated particle solutions can be used in formulations of oral rinses or toothpaste. Also the cetyl-pyridinium chloride-loaded coated particle solutions can be used in formulations of oral rinses or toothpaste. Also the tin fluoride-loaded coated particle solutions can be used in formulations of oral rinses or toothpaste. (Table Removed) Example 2 Results on flat substrates: We first show data for the build-up of PEI and PSS multilayers on quartz. Quartz plates were cleaned using a basic piranha etch (procedure: quartz plates were sonicated in isopropanol-water for 15 minutes followed by immersion in a water-ammonia-hydrogen peroxide etch for 10 minutes at 65°C). These quartz plates bear a negative charge on the surface and are stored under distilled deionized water until they were used. For LbL, a quartz plate was dipped in a 1 mg/ml aqueous solution of PEI containing 1mM (added) sodium chloride. After 30 minutes, the plate was removed and cleaned by rinsing it thrice using distilled deionized water. The plate was then dipped while still wet in a 1 mg/ml solution of PSS containing 1mM (added) sodium chloride. This plate was rinsed thrice after 30 minutes of adsorption and this cycle was repeated to build up addition PEI-PSS layers. Figure 1 shows the UV-Vis data on the plates after repeated build-up of polyelectrolyte layers. PEI does not show any absorbance in the UV-Vis region; however, PSS shows strong absorption at wavelengths upto around 300 nm. Our data clearly reveals the build-up of multi-layers of PSS. PEI and PAAMA are weak polyelectrolytes. Build-up of LbL multilayers using PEI and PAAMA has been demonstrated in the literature (DeLongchamp, D. M., Hammond, P. T. Chem. Mater. 2003, 15, 1165.) and it has been claimed that multilayer build-up in these systems is a sensitive function of pH, rather than the ionic strength of the depositing solutions. Contrary to this report, we find that multilayer build-up is not sensitive to pH in the region of 4 to 7. Rather, we obtain good, reproducible layer build-up by controlling the ionic strength of the polyelectrolyte solutions to 1mM (added) sodium chloride. Characterization of LbL build-up of PEI-PAAMA cannot be done using UV-Vis since neither polyelectrolyte shows significant absorption in the UV-Vis. Therefore, FTIR was used to monitor LbL build-up. We used a clean Si wafer to build-up ten bi-layers of (PEI-PAAMA) and performed FTIR in ATR-FTIR mode using 1000 scans and a LN2-cooled MCT detector. The signal obtained using FTIR was weak, but indicated multilayer formation (Figure 2). We can see the signature of carboxyl groups (indicated by the black line at 1725 cm-1) and of the amino group at 3240cm'1 (this peak appears intense probably because the signal from water adsorbed by the film might contribute to a peak in this region). The peaks are not very distinct above the noise. Figure 2 shows 2 repeat runs from independent samples. Evidence for coating of the silicon wafer by the polyelectrolyte can be qualitatively obtained by observing the wetting behavior of a drop of water on the wafer. A drop of water beads up and dewets a silicon wafer before piranha cleaning. After the piranha etching, the water slightly wets the wafer. However, the water completely wets the silicon wafer after adsorption of the polyelectrolyte. Quartz slides coated with 5 and 10 (bi)layers of PEI-PAAMA were dipped in a solution of cinnamaldehyde and briefly sonicated. The coated slides were then left in cinnamaldehyde overnight to ensure that the cinnamaldehyde is localized in the multilayers. The cinnamaldehyde loaded slides were then rinsed, and then left in water to examine the release of cinnamaldehyde as a function of time. As cinnamaldehyde has a strong UV-Vis absorbance, the release was monitored using UV-Vis. Figure 3 shows the release of the cinnamaldehyde on rinsing with water for the 10 bilayer coated slide. We see (inset) that there is an initial steep decrease in the absorbance from the cinnamaldehyde that then plateaus after about 6 minutes of rinsing. Therefore, it appears that some loosely held cinnamaldehyde is released initially, but some cinnamaldehyde is retained in the multilayers for a long time. It is likely that some of the cinnamaldehyde may have reacted with the primary amine groups in PEI and that this might account for the cinnamaldehyde retention that we are observing. The data for the cinnamaldehyde release from the 5-bilayer coated slide is qualitatively similar, showing an initial steep decrease followed by a plateau. Results on nanoparticle substrates: PEI and PAAMA were assembled on LUDOX and LAPONITE from solutions containing 1mM (added) sodium chloride, the optimized condition obtained from our experiments on flat substrates. Briefly, the procedure for preparing these nanoparticle-polyelectrolyte complexes is as follows: 0.1 mg/ml solutions of either LAPONITE or LUDOXwere prepared by adding distilled deionized water from a Millipore MilliQ system (resistivity = 18.2 Mohm.cm) to measured quantities of Laponite or commercially available Ludox solutions. To 1ml of these solutions, we added 1ml of 1 mg/ml solutions of PEI containing 1mM NaCI. The solutions are stirred, and are clear as water. To this we add 1ml of a 1 mg/ml solution of PAAMA (containing 1 mM NaCI) to build up Nanoparticle-(PEI-PAAMA)1. To obtain multiple layers, we repeat the addition of PEI and PAAMA alternately in the aforementioned manner. In all our experiments, the final solutions are always observed to be clear (water-like). In Figure 3, we see TEM images of as received LAPONITE and LUDOX, and after complexing with (PEI-PAAMA)n, where n is the number of bi-layers. We are unable to resolve the formation of such thin layers on these particles with our electron microscope - however, our TEM shows that we do not have severe aggregation in solution. This explains why our coated nanoparticle solutions are clear. AFM (Nanoscope IV, in contact mode) images were obtained by drying dilute solutions of the nanoparticles (with and without coating) on mica. Figure 6 shows a control sample (plain mica) as well as mica coated with LUDOX. The image of the LUDOX (center) shows dispersed particles, or small lumps comprised of few nanoparticles. However, the coated particles show different behavior in AFM and are much more aggregated relative to the as received LUDOX. While this does not prove that the nanoparticles are being coated, it definitely indicates that exposure to polyelectrolytes changes the nature (viz. surface properties and inter-particle interactions) and aggregation behavior of LUDOX. To examine the interaction of cinnamaldehyde with the polyelectrolyte-nanoparticle complexes, we mixed an excess of cinnamaldehyde (1% by weight of the solution volume) with a solution of the LUDOX-(PEI-PAAMA)5 complexes. In Figure 4, we see that the solution of polyelectrolyte-nanoparticle complexes is completely clear (image to right), while it turns opaque with the excess cinnamaldehyde added. This is because the complexes emulsify the cinnamaldehyde and stabilize its droplets in aqueous solution. This shows that the cinnamaldehyde has a favourable enthalpic interaction with the multilayers and that our polyelectrolyte-nanoparticle complexes can be used to localize cinnamaldehyde. We provide proof-of-concept demonstration of a method for the synthesis of nanoparticle-polyelectrolyte multilayer complexes, and show that these complexes can be used to localize active compounds. By tuning the chemistry of the outer layer of the polyelectrolye multilayers, we can design systems that can anchor on the surface of enamel. Thus, these systems are novel materials for the sustained delivery of actives to the tooth surface. • We have demonstrated the controlled layer-by-layer (LbL) build-up of polymer multilayers on flat subtrates. Polymer multilayers have been built using the following combinations: polystyrene sulfonate and polyethyelene imine; and polyacrylic acid-co-maleic acid (PAAMA) and polyethylene imine (PEI). Layer build-up is characterized using UV-vis and FTIR. • We have demonstrated the loading of polyelectrolyte multilayers with cinnamaldehyde. The cinnamaldehyde is leached out when the loaded multilayers are rinsed with water - however, some cinnamaldehyde is retained in the multilayers even after extensive rinsing. • We have optimized conditions to complex (a) LUDOX and (b) LAPONITE particles using the PAAMA-PEI combination of polyelectrolytes based on our experiments on flat substrates. Aqueous solutions of coated particles are clear. We show that polyelectrolyte treatment of the nanoparticles changes their intra-particle interactions; • We demonstrate that LbL-assemblies on nanoparticles are able to localize cinnamaldehyde in aqueous solution. • The concept of using nanoparticle-polyelectrolyte complexes to anchor on the surface of enamel and to deliver actives in a sustained delivery is demonstrated. We claim 1. An optimized process for the preparation of nanoparticle-polymer complex, as agents for sustained release in oral care product and the said process comprising the steps of: a) preparing an aqueous dispersion of nanoparticles of amorphous silica, titania or synthetic organohectorite (LAPONITE) particles, under stirring, b) adding aqueous solution of carefully optimized concentration of polycation between 5 and 10 mg per m2 of surface area of the colloidal particles, containing sodium chloride to the above said dispersion of nanoparticles and stirring the resultant solution mixture for a period of 1-2 hrs to obtain the polycation coated nanoparticles in the solution mixture, c) adding an aqueous solution of carefully optimized concentration of polyanion between 5 and 10 mg per m2 of surface area of the colloidal particles, containing sodium chloride to the above solution mixture obtained in step (b) and further stirring the resultant solution mixture for a period of 1-2 hrs to obtain the desired bilayer polymer coated nanoparticles, d) further repeating the above said steps (b) and (c) to obtain the multi layer polymer coated nanoparticles, e) stirring the above said resultant multi layer polymer coated nanoparticles with active agent to obtain the desired active agent loaded -polymer coated nanoparticles to obtain the desired formulations for oral rinses or toothpaste. 2. A process as claimed in claim 1, wherein the size of the nanoparticles used in step (a) is in the range of 5-100nm. 3. A process as claimed in claims 1&2, wherein the polyacation used in step (b) is selected from the group consisting of polyethyleneimine (PEI), polyallylamine hydrochloride and polydiallyldimethylammonium chloride. 4. A process as claimed in claims 1-3, wherein the polycation coated nanoparticles obtained are positively charged particles. 5. A process as claimed in claims 1-4, wherein the polyanion used in step ( c) is selected from the group consisting of polystyrene sulfonate (PSS), polyacrylic acid-co-maleic acid (PAAMA), polyacrylic acid (PAA), polyglycolic acid (PGA) anda copolymer of polyacrylic acid and polyglycolic acid. 6. A process as claimed in claims 1-5, wherein the bilayer and multi layered polymer coated nanoparticles obtained in steps (c) & (d) are negatively charged particles. 7. A process as claimed in claims 1-6, wherein the bilayer and multi layered polymer coated nanoparticles obtained in steps (c) & (d) have exposed carboxyl/sulfonyl groups at the their surface. 8. A process as claimed in claims 1-7, wherein the active agent used in step (d) is selected from the group consisting of cinnamaldehyde, cetyl-pyridinium chloride and tin fluoride. 9. A process as claimed in claims 1-7, wherein the aqueous solution of multi layer polymer coated nanoparticles obtained in step (d) is transparent and colourless. 10. A process for the preparation of nanoparticle-polymer complex, as sustain releasing agent for oral care product, as herein described with reference to the examples and drawing accompanying this specification.

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