WO2017137957A1

WO2017137957A1 - Colloidally stable resveratrol nanoparticles with improved bioavailability and half-life and synthesis thereof

Info

Publication number: WO2017137957A1
Application number: PCT/IB2017/050767
Authority: WO
Inventors: Vinaykumar TRIPATHI
Original assignee: Tripathi Vinaykumar
Priority date: 2016-02-11
Filing date: 2017-02-11
Publication date: 2017-08-17

Abstract

The present disclosure relates to a resveratrol delivery system having resveratrol- nanoparticles coated with tree fat coating, wherein upto 90% nanoparticles having a particle size less than 100 nm, characterized in that the nanoparticles are capable of retaining stabilized and unconjugated form of resveratrol at a concentration in a range of 10000 nmoles/liter to up to 40000 nmoles/liter, with half-life of at least 3 hours when administered in mammalian body. The present disclosure further relates to a process for synthesizing resveratrol nanoparticle. Ordinarily the Resveratrol forms conjugates by Sulfonation and glucuronidation in the body. Such Sulfonation and glucuronidation is prevented when resveratrol is synthesized by the disclosed process(s) is administered to a human being or other subject. The administered resveratrol has, inter alia, enhanced threshold bioavailability and half-life.

Description

TITLE

COLLOIDALLY STABLE RESVERATROL NANOPARTICLES WITH IMPROVED BIOAVAILABILITY AND HALF-LIFE AND SYNTHESIS THEREOF

CROSS-REFERENCE TO RELATED APPLICATIONS AND PRIORITY

[001] The present application claims priority to U.S. Provisional Patent Application No. 62/294,050, filed on February 11, 2016, the entirety of which is hereby incorporated by reference.

TECHNICAL FIELD

[002] Invention generally relates to the field of food technology and medicine, more particularly to colloidally stable resveratrol nanoparticles with improved bioavailability and half-life and its synthesis, to alter, enhance, augment, and/or improve its in vivo bioavailability and/or half- life in its free unreacted form, thereby achieving, inter alia, improved health benefits.

BACKGROUND

[003] Resveratrol molecule is a very strong natural biological polyphenol that has antioxidant effect on cellular processes. It has a unique ability to modulate multiple cellular targets and is therefore suitable for the prevention and treatment of wide variety of diseases. One or more beneficial health effects of resveratrol attract interest of patients suffering from wide spectrum of medical and health issues.

[004] Even though resveratrol possesses great potential and is used as a part of many medicines and dietary supplements, the utilization of resveratrol molecule is currently limited due to its unfavorable pharmacokinetic properties. Resveratrol exhibits maximum activity in its free, unreacted form. Being a phenolic compound resveratrol gets rapidly metabolized and eliminated from body, exhibiting low bioavailability in the body when administered orally, which is one of the major limitations. The resveratrol that remains in the bloodstream exist in conjugated form and thus the important antioxidant effect is neutralized. Effectiveness of resveratrol in vivo has been limited by its low bioavailability in the free unreacted form. Various factors such as low concentration of free resveratrol, low stability of free resveratrol in administered formulation, low absorption of free and unreacted resveratrol, low stability of free resveratrol leading to its conversion into less active forms and sulfonation and glucuronidation of resveratrol in the free unreacted form. Synthetic resveratrol having more than 99% purity is known to be effective and bio-active, but is extremely unstable.

[005] Efforts have been made to raise the level of resveratrol in the plasma by giving extra-large doses of resveratrol or by adding various other compounds with resveratrol to suppress the effect of conjugation. But still no effective method or formulation are commercially available.

[006] Furthermore, resveratrol formulation capable of delivering resveratrol in free, unreacted form and retaining it in the bloodstream for prolong period is therefore, much desired.

[007] In the light of foregoing problems, there exists a need for such a formulation which maintains enhanced level of free unreacted resveratrol in the mammalians body so as to be absorbed to its fullest before being eliminated by body for prolong period of time.

[008] The invention described herein below attempts to address the technical problems identified in the preceding paragraphs.

SUMMARY

[009] This summary is provided to introduce concepts related to a resveratrol delivery system (refereed also as system) and process for synthesizing colloidally stable resveratrol nanoparticles with improved therapeutic bioavailability and half-life and the concepts are further described below in the detailed description. It is to be understood that this application is not limited to the particular process steps described in particular order, as there can be multiple possible embodiments which are not expressly illustrated in the present disclosure. The terminology used in the summary or description is for the purpose of describing the particular versions or embodiments only, is not intended to identify essential features of the claimed subject matter nor is it intended for use in determining or limiting the scope of the claimed subject matter.

[0010] In one implementation, a system for delivering resveratrol through colloidally stable resveratrol nanoparticles, is disclosed. The system may comprise resveratrol nanoparticles coated with tree fat, wherein upto 90% nanoparticles have a particle size less than 100 nm, characterized in that the nanoparticles are capable of retaining stabilized and unconjugated form of resveratrol at a concentration in a range of 10000 nmoles/liter to up to 40000 nmoles/liter, with half-life of at least 3 hours when administered in mammalian body.

[0011] In another implementation, a process for coating resveratrol molecules with tree fat to form colloidally stable resveratrol nanoparticle is disclosed. The process may use naturally obtained resveratrol molecules. The process may comprise coating resveratrol molecules with tree fat, to form colloidally stable resveratrol nanoparticle by incubating the resveratrol nanoparticle with the tree fat under constant mechanical stirring, for predefined period of time

[0012] In yet another implementation, the resveratrol nanoparticles coated with tree fat by the above disclosed process have, upto 90% nanoparticles having the particle size less than 100 nm characterized in that the nanoparticles are capable of retaining stabilized and unconjugated form of resveratrol at a concentration in a range of 10000 nmoles/liter to up to 40000 nmoles /liter, with half-life of at least 3 hours when administered in mammalian body.

[0013] In yet another implementation, a process for synthesizing colloidally stable resveratrol nanoparticle is disclosed. The process of obtaining resveratrol molecules using a natural source and coating them with tree fat, comprising steps of: - a) selecting the matured kernels that contain resveratrol;

b) germinating the matured kernels by soaking them in a nutrient medium for prescribed period of time, optimally up to 11 days by maintaining predefined temperature and a varying magnetic strength;

c) drying the sprouted kernels for at least 1 day wherein critical cycles of temperatures are maintained; d) crushing the dried kernels and obtaining purified resveratrol molecules for preparing a formulation having colloidally stable resveratrol nanoparticles;

e) coating resveratrol molecules with tree fat, to form colloidally stable resveratrol nanoparticle by incubating the resveratrol nanoparticle with the tree fat under constant mechanical stirring, for predefined period of time, optimally up to 24 hours.

[0014] In yet another implementation, resveratrol molecules synthesised by the above disclosed process have, upto 90% nanoparticles having the particle size less than 100 nm characterized in that the nanoparticles are capable of retaining stabilized and unconjugated form of resveratrol at a concentration in a range of 10000 nmoles/liter to up to 40000 nmoles /liter, with half-life of at least 3 hours when administered in mammalian body.

DETAILED DESCRIPTION

[0015] Some embodiments of this disclosure, illustrating all its features, will now be discussed in detail. The words "comprising," "having," "containing," and "including," and other forms thereof, are intended to be equivalent in meaning and be open ended in that an item or items following any one of these words is not meant to be an exhaustive listing of such item or items, or meant to be limited to only the listed item or items. It must also be noted that, the singular forms "a," "an," and "the" include plural references unless the context clearly dictates otherwise.

[0016] The exemplary embodiments described herein and claimed hereafter may be suitably practiced in the absence of any recited feature, element or step that is, or is not, specifically disclosed herein. For instance, references in this written description to "one embodiment," "an embodiment," "an example embodiment," and the like, indicate that the embodiment described can include a particular feature, structure, or characteristic, but every embodiment may not necessarily include the particular feature, structure, or characteristic. The disclosed embodiments are merely exemplary of various forms or combinations. Moreover, such phrases are not necessarily referring to some embodiment. Further, when a particular feature, structure, or characteristic is described in connection with an embodiment, it is submitted that it is within the knowledge of one of ordinary skill in the art to affect such feature, structure, or characteristic in connection with other embodiments whether or not explicitly described.

[0017] No or terminology in this application should be construed as indicating any non-claimed element as essential or critical. The use of any and ail examples, or example language (e.g., "such as") provided herein, is intended merely to better illuminate example embodiments and does not pose a limitation on the scope of the claims appended hereto unless otherwise claimed.

[0018] Recitation of ranges of values herein are merely intended to serve as a shorthand method of referring individually to each separate value falling within the range, unless otherwise indicated herein, and each separate value is incorporated into the specification as if it were individually recited herein. Where a specific range of values is provided, it is understood that each intervening value, to the tenth of the unit of the lower limit unless the context dearly dictates otherwise, between the upper and lower limit of that range and any other stated or intervening value in that stated range, is included therein. All smaller subranges are also included. The upper and lower limits of these smaller ranges are also included therein, subject to any specifically excluded limit in the stated range. For example, a range of "about 0.1% to about 5%" or "about 0.1% to 5%" may be interpreted to include not just about 0.1% to about 5%, but also the individual values (e.g., 1 %, 2%, 3%, and 4%) and the sub-ranges (e.g., 0.1% to 0.5%, 1.1 % to 2.2%, 3.3% to 4.4%) within the indicated range.

[0019] System(s) for delivering colloidally stable resveratroi nanoparticles and process(es) for synthetization the same is described. The system may have resveratroi naiiopaiticles -having tree fat coating that delivers the enhanced amount of resveratroi in the mammalians body. The resveratroi nanoparticles having tree fat coating, wherein upto 90% naiiopaiticles having a particle size less than 100 nm, characterized in that the nanoparticles are capable of retaining stabilized and unconjugated form of resveratroi at a concentration in a range of 10000 nmoles/liter to up to 40000 nmoles/liter, with half-life of at least 3 hours when administered in mammalian body. [0020] In order to synthesize colloidally stable resveratroi nanoparticies, wherein upto 90% nanoparticies having a particle size less than 100 nm, characterize in that the nanoparticies are capable of retaining stabilized and unconjugated form of resveratroi at a concentration in a range of 10000 nmoles/liter to up to 40000 nmoles/liter, with half-life of at least 3 hours when administered in mammalian body, the following steps are carried out: - the matured kernels that contains resveratroi, preferably peanut kernels are grown in controlled conditions that leads to;

enhanced concentration of resveratroi in the kernels and;

reduction of resveratroi molecules to smaller dimensions.

After obtaining purified resveratroi molecules, they are coated with a layer of tree fat, to form tree fat coated and stabilized the resveratroi nanoparticle and avoid its agglomeration at pH between 2-12. Ordinarily the resveratroi forms conjugates by Sulfonation and glucuronidation in the liver of human body. Such Sulfonation and glucuronidation is prevented when resveratroi nanoparticle coated with tree fat. As a result, the administered resveratroi has enhanced threshold bioavailability and half-life.

[0021] Referring now to Figure 1 (A) & (B), resveratroi nanoparticies having tree fat coating, wherein upto 90% nanoparticies having a particle size less than 100 nm are illustrated, in accordance with an embodiment of the present subject matter. Although the present subject matter is explained considering that the resveratroi is derived from natural source by the process explained in the disclosure, it may be understood that resveratroi molecules derived from natural sources by other processes than the process explained in the disclosure may also be implemented.

[0022] In one embodiment, the resveratroi nanoparticies are capable of retaining stabilized and unconjugated form of resveratroi at a concentration in a range of 10000 nmoles/liter to up to 40000 nmoles/liter, with half-life of at least 3 hours when administered in mammalian body.

[0023] In one implementation, the resveratroi is derived from natural source, preferably peanut kernels and wherein such tree fat is obtained preferably from Jackfruit [0024] Referring to figure 1, in yet another embodiment, the resveratrol nanoparticle may form a colloid post surface coating with tree fat as observed in SEM analysis. Resveratrol molecule in its colloidal and surface modified form inhibit its glucuronidation and sulfonation, thus slows down or inhibits its hepatic metabolism.

[0025] Referring now to Figure 2, the process 200 for synthesizing colloidally stable resveratrol nanoparticles, wherein upto 90% nanoparticles having a particle size less than 100 nm characterize in that the nanoparticles are capable of retaining stabilized and unconjugated form of resveratrol at a concentration in a range of 10000 nmoles/liter to up to 40000 nmoles/liter, with half-life of at least 3 hours when administered in mammalian body, is illustrated in accordance with an embodiment of the present subject matter.

[0026] The order in which the process 200 is described is not intended to be construed as a limitation, and any number of the described method blocks can be combined in any order to implement the process 200 or alternate process. Additionally, individual blocks may be deleted from the process 200 without departing from the spirit and scope of the subject matter described herein. Furthermore, the process can be implemented using any suitable natural source of resveratrol or combination thereof. However, for ease of explanation, in the embodiments described below, the process 200 may be considered to be implemented in the above described resveratrol delivery system.

[0027] At block 201, matured kernels that contain resveratrol preferably, peanuts are selected.

[0028] At block 202, matured kernels are subjected to germination process by soaking the kernels in a mineral nutrient medium for optimally up to 11 days by maintaining the temperature at 220°C. During the sprouting phase, while kernels are placed in the mineral nutrient medium, a magnetic field is applied to the medium by placing them in a magnetic zone with a varying magnetic strength of 2,000 to 10,000 gauss.

[0029] At block 203, the sprouted kernels are harvested and dried for at least 1 day, in a mechanized auto-control dryer by maintaining the critical cycles of temperatures. [0030] At block 204, dried sprouted kernels are crushed and purified resveratrol molecules are obtained for preparing a formulation having colloidally stable resveratrol nanopariicle. In one embodiment, the resveratrol nanoparticles are purified from crushed kernels by adding the crushed kernels in Phosphate buffered saline solution and the mixture is centrifuged at 10,000- .12,000 rpm for 5-10 minutes, resulting in the pellet formation which contains resveratrol nanoparticles.

[0031] At block 205, resveratrol nanoparticles are coated with tree fat by incubating the resveratrol nanoparticles with the tree fat, under constant mechanical stirring at 400-800 rpm, for up optimally to 24 hours. In one embodiment, the ratio of the tree fat to resveratrol is 3: 1 to 5: 1 in the colloidally stable resveratrol nanoparticles. In one implementation, such tree fat is obtained preferably from Jackfruit

[0032] in yet another embodiment, the process 200 as disclosed in figure 2, enhances the resveratrol content in the kernels. As the kernels are germinated in the mineral nutrient medium at 220°C for optimally up to 11 days, it enhances the resveratrol content in the kernels significantly, within the period of germination. Resveratrol is an antioxidant, synthesized by kernels in response to biotic or abiotic stress or pathogen attack; hence when the kernels are subjected to extreme temperature (abiotic stress) and humidity in presence of mineral rich medium, the kernels up-regulate resveratrol production.

[0033] In one embodiment, during the sprouting phase while kernels are placed in the mineral nutrient medium, a magnetic field is applied to the medium by placing them in a magnetic zone with a varying magnetic strength of 2,000 to 10,000 gauss which leads to rearrangement of mineral ions inside the kernels.

[0034] In yet another embodiment, magnetic field acts as catalyst and the minerals act as reducing agent which leads dot the formation of resveratrol nanoparticle. This resveratrol nanoparticle can enter the nucleus and can control the on/off cycle of genes. [0035] In one preferred embodiment, the kernels are peanut kernels. Out of all natural sources, Peanut kernel is one of the widely available, potent and more consistent source of resveratrol, which contains ample amount of resveratrol with potent antioxidant properties.

[0036] Referring now to Figure 3, each resveratrol nanoparticle coated with tree fat is illustrated. In one implementation, the resveratrol is derived from natural source, preferably peanut kernels and wherein such tree fat is obtained preferably from Jackfruit

[0037] In one embodiment, 4% - 90% particles of the colloidally stable resveratrol nanoparticles have a particle size less than 100 nm.

[0038] In one embodiment, all resveratrol nanoparticles are uniform in size.

[0039] In another embodiment, the ratio of tree fat to resveratrol is 3: 1 to 5: 1 in the colloidally stable resveratrol nanoparticles.

[0040] In another embodiment, each resveratrol nanoparticle comprises up to 1000 molecules of resveratrol.

[0041] An electrostatic repulsion is a measure colloidal stability of tree fat coated nanoparticle and is measured in terms of Zeta Potential which is a measure of surface charge of such coated nanoparticle. An absolute zeta potential value in the range of > -20 to -30 mv represents stable colloidal nanoparticles that will repel and thereby may not agglomerate. Referring to Figure 4, the zeta potential of the coated nanoparticles of the current invention is negatively charged. The trend showed that the nanoparticles are charge stabilized at both lower and higher pH. The range of pH is in between 2 to 12. In one embodiment, the resveratrol nanoparticles having tree fat coating are electrostatically stable since an absolute zeta potential value of the resveratrol nanoparticles having tree fat is in the range of > -20 to -30 mv between pH 2 to 12.

[0042] Referring now to Figure 5 (A) & (B), in yet one embodiment, resveratrol molecule is delivered in the free, unconjugated form at a concentration in the range of 10000 nmoles/liter to up to 40000 nmoles/liter in the blood plasma. Figure 5 (A) and (B) describes the mean and maximum pharmacokinetic parameters, for resveratrol and its metabolites (glucuronides, sulphates) based on the plasma levels of healthy individuals following oral administration of colloidally stable resveratrol nanoparticles. The maximum bioavailability and mean bioavailability of unconjugated resveratrol is upto 40,000 nmol/L and 11,234 nmol/L respectively, with a significant half life of at least 3 hours. The concentration of resveratrol conjugates is very low, only 1.3 % of the orally administered resveratrol underwent metabolism and resulted in formation of resveratrol conjugates whereas 98.7 % of resveratrol is retained in its unconjugated/free form. In one embodiment the coating of tree fat around the resveratrol nanoparticle, stabilizes the resveratrol nanoparticle and avoid its agglomeration at pH between 2-12. Ordinarily the Resveratrol forms conjugates by Sulfonation and glucuronidation in the liver of human body. Such Sulfonaiion and glucuronidation is prevented when Resveratrol nanoparticle coated with tree fat. As a result, the administered resveratrol has enhanced threshold bioavailability and half-life.

[0043] Generally, in the bloodstream, resveratrol molecule can be found essentially in three different forms: glucuronide form, sulfate form, or free form. Resveratrol molecule has high metabolic rate which causes production of conjugated sulfates and glucuronides. Once absorbed, resveratrol molecule is rapidly metabolized by conjugation to glucuronic acid and/or sulfate, forming resveratrol molecule glucuronides, sulfates. Glucuronidation eliminate the therapeutic efficacy of resveratrol molecule thereby resulting in the therapeutically low threshold bioavailability of resveratrol molecule. In one embodiment, the resveratrol nanoparticle surface coated with tree fat enables the resveratrol to retain its free/unconjugated form. In one embodiment, the colloidally stable resveratrol nanoparticle due to its nanoparticle form does not undergoes metabolism and remains free in the blood which further gets absorbed at a cellular level. The tree fat coating of resveratrol nanoparticle provides stability to the nano- formulation at pH value between 2-12 in the mammalian body.

[0044] The oral bioavailability of resveratrol molecule is negligible due to unwanted and quick metabolism and the consequent formation of various metabolites such as glucuronides sulfates. The glucuronide and sulfate conjugates decrease circulating levels of free resveratrol molecule. Thus, metabolism of resveratrol molecule results in relatively small amounts of free resveratrol molecule in the plasma to be delivered to other tissues. In one embodiment, therapeutically low threshold bioavailability of the resveratrol molecule is increased by administering the resveratrol molecule in its colloidally stable nanoparticle form in mammalian body.

[0045] In one embodiment, the half-life of resveratrol molecule is increased. The nano sized resveratrol molecule results in reduced sulfate conjugation and glucuronidation of resveratrol nanoparticle leading to resveratrol molecule's flux across cellular membranes and nucleus and prevents the excretion of the resveratrol molecule hence increases half- life of resveratrol molecule.

[0046] In yet another embodiment, the colloidally stable resveratrol nanoparticle avoids conjugation of resveratrol molecule due its smaller size (size less than 100 nm). Nanoparticle with less than 100 nm does not undergoes metabolism.Thus the half-life of resveratrol molecule is increased.

[0047] In yet another embodiment, the colloidally stable resveratrol nanoparticles are capable of retaining free unconjugated resveratrol molecule in the blood stream for up to 6 hours. In preferred embodiment, the half-life of colloidally stable resveratrol nanoparticles is at least 3 hours in a human clinical study.

[0048] In one embodiment, the tree fat coated resveratrol nanoparticle in the colloidal form is obtained by using the process described in this written description wherein such tree fat is obtained preferably from Jackfruit.

[0049] In a preferred embodiment, the mineral nutrient medium used for soaking the kernels is a mixture of minerals, water and growth media which effects a change in dimension of the resveratrol molecule resulting to its reduction in size, in the presence of magnetic field and formation of a complex with mineral ions. In one embodiment, there are about 92 trace minerals which are present in the nutrient media Although various embodiments for synthesizing colloidally stable resveratrol nanoparticles are described in brief the preceding paragraphs, it is to be understood that this written description is not necessarily limited to the above disclosure of features or methods.

Examples

Below, using examples to illustrate the present invention more specifically. However, the invention is not at all limited to the following examples. The following examples are provided by way of illustration:

Example 1 - bioavailability of orally administered resveratrol

This example shows the bioavailability of orally administered resveratrol with four different systems, out of which a half-life of at least 3 hours with 1.3% of conjugated Resveratrol in plasma (Resveratrol metabolites) is achieved using a resveratrol delivery system disclosed in the disclosure.

Table 1 summarizes the comparative table of bioavailability of orally administered resveratrol by all four systems. The table shows that, when colloidally stable resveratrol nanoparticles are administered as an ingredient in a formulation, the resveratrol molecule is delivered in the free, unconjugated form at a concentration in the range of 10000 nmoles/liter to up to 40000 nmoles/liter in the blood plasma. Furthermore, the system is capable of retaining free unconjugated resveratrol molecule in the blood stream for up to 6 hours. This system has resulted in half-life of at least 3 hours in a human clinical study.

Example 2: Characterization of coated Resveratrol nanoparticles by Dynamic Light Scattering (DLS)

Dynamic light scattering also called as photon correlation spectroscopy determines the hydrodynamic diameter of the nanoparticles and gives information on their colloidal stability. The average hydrodynamic size recorded for the synthesized tree fat coated resveratrol nanoparticles isl()3.8 nm. as shown in table 2. The polydispersity index recorded for the nanoparticles solution is 0.164. Since the polydispersity index of the tree fat coated resveratrol nanoparticle is less than 0.2; it can be inferred that the nanoparticles are monodispersed in nature i.e. all the nanoparticles are uniform in size.

Example 3: Characterization of coated Resveratrol nanoparticies by Zeta potential

The surface charge of the colloidally stable synthesized resveratrol nanoparticies was studied by recording the zeta potential measurements in the pH range of 2 to 12. The zeta potential was negatively charged at lower (i.e below 2 or 2) and higher (i.e 12 or above 12) pH as seen in figure 4. The trend showed that the nanoparticies were charge stabilized at both lower and higher pH. Since nanoparticies showing an absolute zeta potential value in the range of > -20 to -30 mV can be accepted as electrostatically stable.

Example 4 : Characterization of coated Resveratrol nanoparticies by High Resolution Transmission Electron Microscopy (HR-TEM) and Scanning Electron microscopy (SEM)

The most prominent method to analyze the size and shape of nanoparticies is electron microscopy. Thus transmission electron microscopy and scanning electron microscopy was employed to determine the size and shape of resveratrol nanoparticies coated with tree fat. The SEM image (figure 1) revealed spherically shaped resveratrol nanoparticies. In HR-TEM the tree fat coating on resveratrol nanoparticies was clearly evident with the size ranging from 65 nm-95 nm (figure 3). The mean diameter of the synthesized tree fat coated resveratrol nanoparticies was estimated to be 80.6 nm.

Claims

I CLAIM:

1. A resveratrol delivery system having colloidally stable resveratrol nanoparticles having tree fat coating, wherein upto 90% nanoparticles have a particle size less than 100 nm, characterized in that the nanoparticles are capable of retaining stabilized and unconjugated form of resveratrol at a concentration in a range of 10000 nmoles/liter to up to 40000 nmoles/liter, with half-life of at least 3 hours when administered in mammalian body.

2. The resveratrol delivery system as claimed in claim 1, wherein the colloidally stable resveratrol nanoparticles have a zeta potential below -20 mv between a pH range of 2 to 12.

3. The resveratrol delivery system as claimed in claim 1 , wherein ratio of tree fat to resveratrol is in between 3: 1 to 5: 1 in the colloidally stable resveratrol nanoparticles.

4. The resveratrol delivery system, as claimed in claim 1, wherein the coating of tree fat stabilizes the resveratrol nanoparticle and inhibits its agglomeration at pH ranging between 2 to 12 inside the mammalian body.

5. The resveratrol delivery system as claimed in claim 1, wherein the resveratrol is released in mammalian body only at pH above 12.

6. The resveratrol delivery system, as claimed in claim 1, wherein each colloidally stable resveratrol nanoparticle comprises upto 1000 molecules of resveratrol.

7. The resveratrol delivery system, as claimed in claim 1, wherein the colloidally stable resveratrol- nanoparticles are delivered in the form of oral formulation.

8. The resveratrol delivery system, as claimed in claim 1, wherein resveratrol molecule is obtained from natural source, preferably peanut kernels.

9. A process for coating a resveratrol nanoparticles having tree fat coating, comprises the steps of:

a) obtaining resveratrol molecules;

b) coating resveratrol molecules with tree fat, to form colloidally stable resveratrol nanoparticle by incubating the resveratrol nanoparticle with the tree fat under constant mechanical stirring, for predefined period of time;

wherein upto 90% nanoparticles having a particle size less than 100 nm characterized in that the nanoparticles are capable of retaining stabilized and unconjugated form of resveratrol at a concentration in a range of 10000 nmoles/liter to up to 40000 nmoles /liter, with half-life of at least 3 hours when administered in mammalian body.

10. The process, as claimed in claim 9, wherein a ratio of tree fat to resveratrol is in between 3: 1 to 5: 1 in the colloidally stable resveratrol nanoparticles.

11. A process for synthesizing colloidally stable resveratrol nanoparticle comprising the steps of:

a) selecting the matured kernels that contain resveratrol;

c) drying the sprouted kernels for at least 1 day, wherein critical cycles of temperatures are maintained;

d) crushing the dried kernels and obtaining purified resveratrol molecules for preparing a formulation having colloidally stable resveratrol nanoparticles;

e) coating resveratrol molecules with tree fat, to form colloidally stableresveratrol nanoparticle by incubating the resveratrol nanoparticle with the tree fat under constant mechanical stirring, for predefined period of time, optimally up to 24 hours;

wherein upto 90% coated nanoparticles having a particle size less than 100 nm, characterize in that the nanoparticles are capable of retaining stabilized and unconjugated form of resveratrol at a concentration in a range of 10000 nmoles/liter to up to 40000 nmoles/liter, with half-life of at least 3 hours when administered in mammalian body.

12. The process as claimed in claim 11, wherein the germination of kernels at controlled environment enhances the resveratrol content in the kernels.

13. The process as claimed in claim 11, wherein the colloidally stable resveratrol nanoparticles have a zeta potential below -20 mv between a pH range of 2 to 12

14. The process, as claimed in claim 11, wherein a ratio of resveratrol to the tree fat is in between 3: 1 to 5: 1, in the colloidally stable resveratrol nanoparticles.

15. The process, as claimed in claim 11, wherein the resveratrol is derived from natural source, preferably peanut kernels.