| Title of Invention | MULTI-LAYER NANOCOMPOSITE |
|---|---|
| Abstract | [0035] A multi-layer nanocomposite is provided. The nanocomposite includes a negatively charged polymer layer comprising a first drug and a positively charged polymer layer encapsulating the negatively charged polymer layer and comprising a second drug. The negatively charged polymer layer and the positively charged polymer layer are held together by electrostatic forces. |
| Full Text | BACKGROUND [0001] The invention relates generally to nanocomposites, and more specifically to multi-layer nanocomposites comprising hydrophilic and hydrophobic layers. [0002] Multifuncional nanosystems are typically used for the treatment of various diseases such as cancer, hypothermia and the like. A system that can provide chemical and radiation therapy together is an example of a multifunctional system. Nanocomposites are widely used as multifunctional systems due to the ease of preparation and stability in biological fields and during storage. [0003] Typically, a part of such nanocomposites include multiple layers of hydrophobic polymers and hydrophilic polymers. The layers are generally held together using a surfactant material. Further, the hydrophobic and hydrophilic layers may be loaded with separate drugs thus making the nanocomposite a very effective multifunctional system. [0004] Nanocomposites may also magnetic nanoparticles loaded in to the hydrophobic layer. This loading makes the system more effective. Magnetic nanoparticles can be used for various biomedical applications such as cell labeling/cell separation, magnetofection to facilitate gene delivery, contrast agents for magnetic resonance imaging (MRI), local hyperthermia in response to an external alternating magnetic field to selectively destroy cancer cells, and as magnetically targeted carrier system in drug delivery applications. [0005] However, current techniques used for synthesis of nanocomposites generally lack the ability to encapsulate both hydrophilic and hydrophobic drug in the same nanocomposite. Therefore, there is a need for a multifunctional system that delivers both a hydrophobic and a hydrophilic drug effectively. BRIEF DESCRIPTION [0006] Briefly, according to one embodiment of the present invention, a nanocomposite is provided. The nanocomposite includes a negatively charged polymer layer comprising a first drug and a positively charged polymer layer encapsulating the negatively charged polymer layer and comprising a second drug. The negatively charged polymer layer and the positively charged polymer layer are held together by electrostatic forces. [0007] In another embodiment, a method of synthesizing a nanocomposite is provided. The method includes preparing a first layer of a negatively charged polymer, emulsifying a first drug in the first layer, preparing a second layer of a positively charged polymer, emulsifying a second drug in the second layer and encapsulating the first layer with the second layer to form the nanocomposite, wherein the first layer and the second layer are held together by electrostatic forces. DRAWINGS [0008] These and other features, aspects, and advantages of the present invention will become better understood when the following detailed description is read with reference to the accompanying drawings in which like characters represent like parts throughout the drawings, wherein: [0009] FIG. 1 illustrates one embodiment of a nanocomposite implemented according to aspects of the present technique; [0010] FIG. 2 is a flow chart illustrating a method for synthesizing a nanocomposite according to aspects of the present technique; [0011] FIG. 3 is a graphical representation of particle size distribution of the nanocomposite consisting of two polymeric layers and magnetic nanoparticles, implemented according to aspects of the present invention; and [0012] FIG. 4 is a graphical representation of zeta potential of the nanocomposite consisting of two polymeric layers and magnetic nanoparticles, implemented according to aspects of the present invention. DETAILED DESCRIPTION [0013] As discussed in detail below, embodiments of the present technique function provide nanocomposites for use in applications such as drug delivery, therapy, etc. References in the specification to "one embodiment", "an embodiment", "an exemplary embodiment”, indicate that the embodiment described may include a particular feature, structure, or characteristic, but every embodiment may not necessarily include the particular feature, structure, or characteristic. Moreover, such phrases are not necessarily referring to the same 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 skilled in the art to affect such feature, structure, or characteristic in connection with other embodiments whether or not explicitly described. [0014] Turning now to drawings and referring first to FIG. 1, a nanocomposite including multiple layers implemented according to aspects of the present technique. The nanocomposite 10 includes a negatively charged layer 12 and a positively charged layer 18. In one embodiment, the negatively charged layer 12 comprises a negatively charged polymer template and the positively charged layer 18 comprises a positively charged polymer template. In one embodiment, the negatively charged polymer layer 12 is encapsulated by the positively charged polymer layer 18. The negatively charged polymer layer 12 and the positively charged polymer layer 18 are held together by electrostatic forces. [0015] In one embodiment, the negatively charged polymer layer 12 comprises a hydrophobic polymer. Examples of hydrophobic polymers include poly lactic-co-glycolic acid (PLGA), poly lactic acid (PLA), silica among others. In the illustrated embodiment, PLGA is used to form the negatively charged polymer layer. PLGA is particularly useful in drug delivery applications as it is biocompatible and its sub-products are nontoxic. Moreover, the monomeric units of PLGA, lactic and glycolic acid occur naturally in the human body and are easily eliminated through the glycolytic pathway as carbon dioxide and water. [0016] The negatively charged polymer layer template 12 further includes a first drug 16. The first drug 16 is a hydrophobic drug such as a hydrophobic anticancer drug, for example, bicalutamide, tamoxifen, taxol. In a further embodiment, the negatively charged polymer layer template 12 comprises multiple magnetic nanoparticles. The magnetic nanoparticles are particularly helpful in cell labeling/cell separation, magnetofection and for use as contrast agents for magnetic resonance imaging applications. [0017] The positively charged polymer layer 18 includes a hydrophilic polymer. Examples of hydrophilic polymers include chitosan, DEAE Dextran, protamine sulphate, poly lysine, poly arginine, gelatin, polyallylamine hydrochloride among others. In the illustrated embodiment, chitosan is used to form the positively charged polymer layer. Chitosan is used as food supplement and particularly suited for drug delivery as it is biocompatible and biodegradable. Chitosan nanoparticles increase circulation time of a drug in the blood and decrease uptake of a drug by the reticulo-endothelial system. [0018] In one embodiment, the positively charged polymer layer 18 includes a second drug 20. The second drug 20 is a hydrophilic drug such as a hydrophilic anticancer drug or a hydrophilic anti-inflammatory agent. Examples of the second drug include cisplatin, doxorubicin, 5-Fluorouracil as the anti-cancer drug and dicolfenac sodium, mefenamic acid, mesalamine etc. The manner in which the nanocomposite is synthesized is described in further detail below. [0019] FIG. 2 is a flow chart illustrating a method for synthesizing a nanocomposite according to aspects of the present technique. The technique below describes a two layer nanocomposite, however it should be understood by one skilled in the art that the technique describe below can be used to synthesize a multi-layer nanocomposite as well. Each step is described in further detail below. [0020] At step 22, a first layer of negatively charged polymer layer is prepared. In one embodiment, the first layer of negatively charged polymer comprises a hydrophobic polymer. Examples of hydrophobic polymers include poly lactic-co-glycolic acid (PLGA), silica and the like. In one specific embodiment, the hydrophobic polymer includes Polyoly (D, L-lactide-co-glycolide) (PLGA), with a lactide to glycolide ratio of 50:50. [0021] At step 24, a first drug emulsified in the first layer of negatively charged polymer template. In one specific example, 30mg magnetic nanoparticle, 3mg of bicalutamide and 30mg PLGA are dissolved in 5ml of dichloromethane to form an organic phase. The organic phase is then added to 10ml of an aqueous phase including 3% Polyvinyl alcohol (PVA) as a stabilizer. After mutual saturation of the organic phase and the aqueous phase, a mixture of the aqueous phase and the organic phase is emulsified for 10 minutes with an ultrasonicator. Subsequently, after solvent evaporation, products obtained are purified with three cycles of centrifugation at 20000 rpm. The precipitated products are redispersed in 10 mM sodium phosphate buffer (2ml, pH 7.4). Due to the presence of amphiphilic PVA, the products are well suspended in the aqueous medium. The product thus formed is Bicalutamide loaded magnetic PLGA nanocomposite. In a further embodiment, magnetic nanoparticles are added to the first layer of negatively charged polymer layer. The magnetic nanoparticles used in may be made of different elements. Typical examples are Fe3O4, MnFe3O4, and the entities containing magnetic elements such as Cobalt, Nickel and the like. These can be prepared by various means of procedures. In one embodiment, Fe3O4 is prepared by co-precipitation procedure. [0022] At step 26, a second layer of positively charged polymer layer is formed. In one embodiment, the second layer is formed of a hydrophilic polymer. Examples of hydrophilic polymers include chitosan, DEAE Dextran, protamine sulphate, poly lysine, poly arginine, gelatin, polyallylamine hydrochloride. In the illustrated embodiment, the second layer of positively charged polymer is chitosan of medium molecular weight. [0023] At step 28, a second drug, such as, for example the second drug 20 of FIG. 1 is emulsified. In one embodiment, diclofenac sodium is added to the chitosan polymers. [0024] At step 30, the first layer 12 is encapsulated with the second layer 18 to form the multi-layer nanocomposite as shown in step 32. More specifically, the first layer having negative surface charge is coated and encapsulated with the positively charged second layer. In one embodiment, the chitosan layer is coated PLGA layer by a simple mixing method. First a specific quantity of bicalutamide magnetic PLGA layer in 1ml of phosphate buffered saline is mixed with desired amount of chitosan (0-10 mg) and stirred for 2 hours and centrifuged at 15000 rpm for purification. [0025] It may be understood that the chitosan coated magnetic PLGA nanocomposite loaded with bicalutamide and diclofenac sodium as described as above is an illustrative example of dual drug delivery system for cancer therapy. It may be appreciated by one skilled in the art that the nanocomposite 10 may comprise other biocompatible negatively and positively charged polymers loaded with other hydrophobic and hydrophilic drugs respectively. [0026] Further addition of magnetic nanoparticles to the nanocomposite is described herein only as an example of additional functionality especially in applications of hyperthermia provided for cancer therapy. Other nanoparticles may be added to the nanocomposite for providing other benefits. For example, the nanoparticles may comprise gold nanostructures for photothermal therapy, monoclonal antibodies for targeted therapy or contrast agent molecules for diagnostic applications. [0027] Several techniques may be used to analyze the size of a nanocomposite synthesized using the techniques described above.. In one embodiment, the size of the nanocomposite is analyzed using laser scattering. The zeta potential of nanocomposite is measured by zeta analyzer. The size of the magnetic nanoparticles measured by differential light scattering techniques was 40±10nm with polydispersity index 0.120±0.045. The measurement indicates that the magnetic nanoparticle has narrow size distributions. [0028] . In one embodiment, the size of hydrophobic and hydrophilic drug loaded chitosan coated magnetic PLGA nanocomposite was approximately 380±20 nm. The increase in size is due to the chitosan coating on the magnetic PLGA nanocomposite. It was however noted that all nanocomposites have a polydispersity index of less than 0.200 thereby indicating a narrow size distribution. [0029] In a further embodiment, the first layer with PLGA and magnetic nanoparticles was incubated with varying amount of chitosan solutions to optimize the surface coating process. The surface coating of chitosan on the magnetic PLGA nanoparticles was assessed by monitoring size and zeta potential value by dynamic light scattering method and zeta analyzer. [0030] As shown in FIG. 3, the zeta potential value of magnetic PLGA nanoparticles increased from -30± 2.07 to 30±1.2 mV with increase weight ratio of chitosan to PLGA . The surface charge of chitosan coated magnetic PLGA nanoparticles were 22mV at a weight ratio of 0.2. [0031] As shown in FIG. 4, the size of magnetic PLGA nanocomposite coated with chitosan polymer increased from 160±15 nm to 400±20 nm. Particle size of 313±20 nm was the lowest particles size after chitosan coating. In one embodiment, the weight ratio of chitosan /PLGA layer is 0.2 during coating conditions. [0032] The various aspects of the nanocomposite described hereinabove may be used for drug delivery and other therapeutic applications. As described above, the nanocomposite provides a multifunctional system for cancer therapy by providing hydrophilic and hydrophobic anticancer drug and magnetic nanoparticles for hyperthermia. As will be appreciated by those skilled in the art, the use of such a nanocomposite facilitates multimodal therapy required for diseases like cancer. [0033] While only certain features of the invention have been illustrated and described herein, many modifications and changes will occur to those skilled in the art. It is, therefore, to be understood that the appended claims are intended to cover all such modifications and changes as fall within the true spirit of the invention. [0034] CLAIMS: 1. A nanocomposite comprising: a negatively charged polymer layer comprising a first drug; and a positively charged polymer layer encapsulating the negatively charged polymer layer and comprising a second drug, wherein the negatively charged polymer layer and the positively charged polymer layer are held together by electrostatic forces. 2. The nanocomposite of claim 1, wherein the negatively charged polymer layer comprises a hydrophobic polymer. 3. The nanocomposite of claim 1, wherein the positively charged polymer layer comprises a hydrophilic polymer. 4. The nanocomposite of claim 1, wherein the negatively charged polymer layer further comprises a plurality of magnetic nanoparticles. 5. The nanocomposite of claim 1, wherein the negatively charged polymer layer and the positively charged polymer layer are biocompatible. 6. A method of synthesizing a nanocomposite comprising: preparing a first layer of a negatively charged polymer, emulsifying a first drug in the first layer, preparing a second layer of a positively charged polymer, emulsifying a second drug in the second layer, and encapsulating the first layer with the second layer to form the nanocomposite, wherein the first layer and the second layer are held together by electrostatic forces. 7. The method of claim 5, wherein the first layer further comprises a plurality of magnetic nanoparticles. 8. The method of claim 5, wherein the first layer comprises a hydrophobic polymer and the second layer comprises a hydrophilic polymer. 9. The method of claim 5, wherein the first layer further comprises a plurality of magnetic nanoparticles. 10. The method of claim 5, wherein the first layer and the second layer are biocompatible layers. Dated this the 21st day of March, 2011 S Afsar Attorney for the Applicant Registration No. IN/PA-1073 MULTI-LAYER NANOCOMPOSITE ABSTRACT [0035] A multi-layer nanocomposite is provided. The nanocomposite includes a negatively charged polymer layer comprising a first drug and a positively charged polymer layer encapsulating the negatively charged polymer layer and comprising a second drug. The negatively charged polymer layer and the positively charged polymer layer are held together by electrostatic forces. |
|---|
| Patent Number | 271416 | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Indian Patent Application Number | 811/MUM/2011 | ||||||||||||||||||
| PG Journal Number | 09/2016 | ||||||||||||||||||
| Publication Date | 26-Feb-2016 | ||||||||||||||||||
| Grant Date | 19-Feb-2016 | ||||||||||||||||||
| Date of Filing | 21-Mar-2011 | ||||||||||||||||||
| Name of Patentee | INDIAN INSTITUTE OF TECHNOLOGY BOMBAY | ||||||||||||||||||
| Applicant Address | Powai Mumbai Maharashtra 400076 INDIA | ||||||||||||||||||
Inventors:
|
|||||||||||||||||||
| PCT International Classification Number | A61K 47/48, A61K9/14, A61K 9/50 | ||||||||||||||||||
| PCT International Application Number | N/A | ||||||||||||||||||
| PCT International Filing date | |||||||||||||||||||
PCT Conventions:
|
|||||||||||||||||||