A method for coating a medical device with NANO-encapsulated drug using membrane technology

Abstract

The present invention relates to a method for coating a medical device with nano- encapsulated drug using membrane technology. The said medical device is for interventional procedures. The invention discloses the design, formulation, technology features and potential clinical applications, emphasizing its role in improving outcomes in interventional procedures.

Description

[0001]“A METHOD FOR COATING A MEDICAL DEVICE WITH NANO- ENCAPSULATED DRUG USING MEMBRANE TECHNOLOGY” Field of Invention: 5 The present invention relates to a Nano encapsulated Drug coated medical device and a method of preparation thereof for interventional procedures. More particularly the invention relates to Nano encapsulated Drug coated balloon prepared by Membrane Technology. 10 Background of the invention: Peripheral Artery Disease (PAD) refers to the narrowing or blockage of arteries outside the heart, commonly occurring in the lower extremities (legs and feet) and Coronary Artery Disease (CAD) involves the narrowing or blockage of the coronary arteries, which supply oxygen-rich blood to the heart muscle. Both PAD, 15 CAD is primarily caused by atherosclerosis, where plaque build-up restricts blood flow to the heart and for the treatment of these conditions many Interventional procedures using medical devices such as drug coated stent, bare metal stent, drug coated balloon etc. have been utilised. Drug-coated stents are typically used in PAD and CAD. 20 A drug-coated stent is a small, expandable mesh tube usually made of metal (such as stainless steel or cobalt-chromium) or polymer. It is mounted on a balloon-tipped catheter and guided to the narrowed or blocked artery in a way that the medicine is released gradually via the stent to prevent cell proliferation. The stents reduce acute 25 vessel closure in coronary arteries and minimize vessel recoil in peripheral and Coronary interventions, Drug Eluting Stents (DES) has substantially improved clinical outcomes. However, these advancements have their own set of drawbacks, including late stent thrombosis (ST), delayed healing, permanent caging effect, stent fractures, and the occurrence of in-stent restenosis (ISR). Further Late stent thrombosis, a potentially serious complication, raised questions about the long-term safety of DES. Delayed healing and the permanent presence of the stent structure have been associated with persistent inflammatory responses. 5 On the other hand, drug coated balloon (DCB) is one of the notable types of interventional medical device for the treatment. DCB device pave their way on reoccurrence of the blockage where the stenting has been done, there is a need for treatment of that vessel with the DCB device. Also, 10 the narrow vessel must be treated with DCB to address the coronary artery disease (CAD). The drug eluting stent platform made of the metal alloy like cobalt chromium, platinum-chromium, stainless-steel chromium etc. which remains permanently inside the coronary blood vessel, whereas DCB device is a good choice to deliver the active therapeutics agent by means of the balloon inflation. DCB are 15 designed to address arterial blockages by combining the principles of balloon angioplasty with localized drug delivery. In drug-coated balloons (DCBs), the coating formulation typically comprises an active pharmaceutical agent (the therapeutic drug) along with auxiliary agents or 20 excipients. The active pharmaceutical agent is the therapeutic substance intended to exert the desired pharmacological effect at the target site, often aimed at preventing restenosis or treating a specific vascular condition. US5102402 relates to Releasable coatings on balloon catheters. Balloon catheters 25 are prepared to include a coating of body affecting chemicals on the exterior of the balloon. The coating releases from the balloon when the balloon is inflated into contact with the lumen to be treated. The device provides accurate placement of the dosage required at the location in need of treatment. The coating preferably includes drugs in microcapsules or microspheres. The catheters are especially useful in 30 balloon angioplasty procedures. US5370614A relates to a balloon catheter and includes a sheath surrounding the balloon, the sheath having a longitudinal line of weakness and a drug-containing viscous matrix material intermediate between the balloon and the sheath such that when the balloon is positioned and inflated in the body lumen it causes the sheath 5 to burst at the line of weakness and release viscous matrix material onto said body lumen. The device provides accurate placement of the dosage required at the location in need of treatment. The catheter is especially useful in balloon angioplasty procedures. 10 WO2009066330A1 relates to balloon for the treatment of stenosis and method for manufacturing the balloon. WO0045744A1 relates to surface protection method for stents and balloon catheters for drug delivery. 15 US2011160698A1 relates to Balloon Catheter for Treating Stenosis of Body Passages and for Preventing Threatening Restenosis wherein the coating method uses a coating device having a volume measuring device for releasing a measurable amount of a coating solution by means of a dispensing device specifically onto the 20 surface of the catheter balloon. US2012059316A1 provides Coating Process for Drug Delivery Balloons Using Heat-Induced Rewrap Memory. 25 WO2016183421A1 drug coated medical devices of a therapeutic coating comprising a polydopamine coated therapeutic agent disposed on a surface of the expandable medical device. In some instances, the therapeutic agent may comprise Everolimus. 30 EP2442840A2 drug coated balloon catheter and pharmacokinetic profile. A drug delivery balloon is provided comprising a balloon having a surface, and a coating disposed on at least a portion of the balloon surface, the coating including a cytostatic therapeutic agent, an excipient, and a plasticizer. In accordance with the subject matter, at least 30% of the coating transfers from the balloon surface within two minutes after inflation of the balloon. Alternatively, at least 30% of the coating 5 transfers from the balloon surface within one minute after inflation. The coating results in an effective pharmacokinetic profile of a cytostatic therapeutic agent in a vasculature or target tissue. However, there was a need for medical device technology that can rapidly, 10 efficiently, reproducibly and safely transfer a drug from the surface of a percutaneous medical device (a coating) onto / into a specific treatment site in the body. Therefore, inventors tried to develop the nanoparticles which would rapidly and easily disperse the drug. 15 For instance, EP2658527A2 provides nanoparticle and surface-modified particulate coatings, coated balloons, and methods therefore. Further, EP ‘527 uses nanoemulsion via homogenization. Further, it has been found that the homogenization technology is inefficient, primarily with respect to precise size- control of the drug nanoparticles. Furthermore, the disclosure of EP ‘527 does not 20 suggest sustained release of upto 1 day which may not be efficient in case of severe inflammation. In response to the challenges, Nano-encapsulated-Drug coated Balloon (NE-DCB) emerged as an innovative, non-stent alternative to address the drawbacks associated 25 with DES. The fundamental concept behind Everolimus / Drug coated Balloon involves delivering therapeutic agents directly to the target lesion using a balloon without the need for a permanent implant. This approach offers the potential for sustained anti-restenosis therapy while overcoming the limitations imposed by permanent stent implants. However, existing methods often rely on polymeric reservoirs or Homogenizer, limiting encapsulation efficiency, uniformity, stability, and bioavailability. Thus, there exists a need for Nanoencapsulated drug-coated balloon prepared by 5 Membrane Technology, offering precise particle size control, enhanced stability, and predictable drug release. Objects of the invention An object of the present invention is to provide a formulation of Nano encapsulation 10 of drug / API using the membrane technology and spraying of Nano-encapsulated therapeutic agent on a medical device to increase its bioavailability at target site. Another object of the present invention is to provide a robust and scalable method for the preparation of a nanoencapsulated drug coating utilizing membrane 15 technology, the method comprising sequential steps of solution preparation, membrane emulsification under controlled laminar flow (membrane technology), dialysis, pre-freezing, lyophilization, dilution, and precise spraying application; wherein the resultant coating formulation is configured to achieve controlled release, burst release, and targeted delivery of the therapeutic agent at the lesion 20 site, while obviating the need for permanent vascular implants. Yet another object of the invention is to provide a sustained release of a drug for extended period of time. 25 Summary of the Invention: The present invention provides a method for coating a medical device with a nanoencapsulated drug formulation utilizing membrane technology, wherein the formulation comprises nanoparticles of an active pharmaceutical ingredient (API) / Drug, encapsulated within amphiphilic molecules by membrane technology 30 under controlled laminar flow conditions, and subsequently applied onto the surface of a balloon by a spraying process to enhance bioavailability of the drug at the target site. In an aspect the invention pertains to a method of the coating applied to drug-coated 5 medical device utilizing membrane technology that comprises the steps of: 1. Preparing an organic solution comprising one or more amphiphilic molecules and drug / API dissolved in an organic solvent; 2. Preparing an aqueous buffer solution; 3. Introducing the organic solution as a dispersed phase through a precision- 10 engineered porous stainless-steel membrane (20–1000 nm) into the aqueous buffer as a continuous phase, under controlled laminar flow; 4. Obtaining nanoparticles with an average size of 20–500 nm; 5. Subjecting the formulation to dialysis, pre-freezing, and lyophilization to yield a dry stable powder; 15 6. Reconstituting and diluting the powder with organic solvent to prepare a sprayable solution; and 7. Spraying the solution uniformly on the medical device, optionally along with polymer layers and / or protective topcoat layers. This process ensures uniform particle size, high encapsulation efficiency, enhanced 20 drug stability, and improved bioavailability at the lesion site. In yet another aspect, the invention provides a polymer layer which is adapted to release the active agent over an extended duration of approximately 30 to 90 days. Brief Description of the Figures: 25 Figure 1: Illustrates the Membrane Technology process. Figure 2: Illustrates a 2D depiction of the balloon, representing its distal and proximal sections. Figure 3: Illustrates the balloon’s surface post the application of coating formulations. 30 Figure 4: Illustrates the Dynamic light scattering Chromatogram. Figure 5: Illustrates the Drug release analysis. Figure 5.1: Illustrates the Drug release Chromatogram at 20 sec. Figure 5.2: Illustrates the Drug release Chromatogram at 40 sec. Figure 5.3: Illustrates the Drug release Chromatogram at 60 sec. Figure 5.4: Illustrates the Drug release Chromatogram recovery. 5 Detailed Description of the Drawings: Figure 1 describes a Membrane Technology process wherein the said method includes the flow of continuous and dispersed phases through the stainless-steel membrane, where precision-engineered pores (20–1000 nm) facilitate conversion 10 of larger particles into nanosized particles, supporting the encapsulation process. Controlled laminar flow and simultaneous initiation of both phases contribute to the formation of high-quality nanoencapsulated drugs at the product outlet. Figure 2 describes a 2D depiction of the balloon, representing its distal and proximal sections. 15 Detailed Description of the Invention The invention will now be described in detail with reference to certain preferred and optional embodiments, so that various aspects thereof may be more fully understood and appreciated. As used herein, the following terms and phrases shall 20 have the meanings set forth below. Prior to describing the embodiments of the present invention, it should be noted that these embodiments primarily relate to formulations involving the nanoencapsulation of drugs or active pharmaceutical ingredients (APIs) using membrane technology. Accordingly, the formulation components and methodological steps are described with emphasis on the specific 25 details necessary to understand the embodiments of the invention, without including information that would be readily apparent to those skilled in the art upon review of this description. Unless specified otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which 30 this invention pertains. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, the preferred methods and materials are described. Unless stated to the contrary, any of the words “contains,” “containing,” 5 “including,” “includes,” “comprising,” and “comprises” shall mean “including without limitation” and shall not be construed to limit any general statement that it follows to the specific or similar items or matters immediately following it. Embodiments of the invention are not mutually exclusive and may be implemented in one or more combinations. The described embodiments and disclosed examples 10 are provided for purposes of illustration rather than limitation. Further, words such as “a,” “an,” “at least,” and “the” should be construed to cover singular as well as plural quantities of the elements immediately following them. “Drug” or “API,” according to the present invention, includes both therapeutic 15 agents and diagnostic agents. The terms “drug,” “active,” “therapeutic agent,” and “diagnostic agent” may be used interchangeably throughout the specification and shall imply the same meaning. “Excipients,” according to the present invention, include amphiphilic molecules. 20 The terms “excipients” or “amphiphilic molecules” may be used interchangeably throughout the specification and shall imply the same meaning. The invention provides a method for coating a medical device with nanoencapsulated drug formulation utilizing membrane technology, wherein the 25 methods comprises use of a porous stainless-steel membrane which facilitates controlling the size of nano particles in range of 20–1000 nm. The judicious selection of particle size is essential for precise and efficient drug delivery to a target site, particularly within a blood vessel. The nanoencapsulated active substance and coating of the active substance using a customized spraying process, while maintaining drug stability, can address the intended use effectively for arterial stenosis. 5 In an embodiment, the present invention further provides a drug-coated medical device coating solution utilizing membrane technology. The present invention provides a drug formulation utilizing nanoencapsulation, 10 wherein drug particles or molecules are encapsulated within nano-sized carriers. The drug is enveloped within excipients, facilitated by the membrane technology. This encapsulation technique enables precise control over drug kinetics, thereby enhancing targeted delivery. 15 Further, the nanoencapsulated formulation is devoid of polymeric reservoir matrices, i.e. nanoencapsulated formulation does not contain any polymer-based structures. In an embodiment of the present invention, the drug is encapsulated by nanoencapsulation. 20 Accordingly, the present invention, in various embodiments, provides enhanced precision and efficiency of drug delivery to a target site, particularly within a blood vessel. By utilizing nanoencapsulation in combination with a tailored coating or spraying process, the system enables controlled and localized release of therapeutic 25 agents. This configuration facilitates uniform and focused drug application, for example, on the surface of a drug-delivery balloon, thereby improving therapeutic efficacy while minimizing off-target effects and systemic exposure. In one of the embodiments, the polymer layer and / or the nanoencapsulated layer is configured to facilitate a tailored release profile comprising an initial burst release 30 followed by a sustained long-term release of the active agent. Accordingly, in an embodiment, the solution preparation for nanoencapsulation of the drug involves the steps described herein. Preparation of Organic Solution 5 The method includes the preparation of an organic solution comprising one or more amphiphilic molecules along with one or more drug / API, wherein the amphiphilic molecules and drug / API are dissolved in one or more organic solvents. The one or more amphiphilic molecules and drug / API may be selected from, but are not limited to, phospholipids, sterols, PEGylated lipids, non-ionic surfactants, anti-restenotic 10 agents, anti-proliferative agents, immunosuppressants, chemotherapeutic agents, poorly water-soluble pharmaceutical compounds, drugs for the treatment of coronary artery disease (CAD), drugs for the treatment of peripheral artery disease (PAD), and anti-inflammatory agents. 15 Examples of suitable amphiphilic molecules include, but are not limited to, dipalmitoylphosphatidylcholine (DPPC), dioleoylphosphatidylethanolamine (DOPE), distearoylphosphatidylethanolamine (DSPE), dioleoylphosphatidylcholine (DOPC), distearoylphosphatidylcholine (DSPC), palmitoyloleoylphosphatidylcholine (POPC), PEGylated lipids (e.g., PEG 2000- 20 DSPE, PEG 5000-DSPE), cholesterol, β-sitosterol, polysorbate 80 (Tween 80), polysorbate 20 (Tween 20), poloxamer 407 (Pluronic F127), poloxamer 188 (Pluronic F68), sorbitan monooleate (Span 80), cationic lipids (e.g., DOTAP, DDAB), and bile salts (e.g., sodium cholate, sodium deoxycholate). Examples of suitable drug / API include, but are not limited to, everolimus, 25 rapamycin, drugs from the limus family, and paclitaxel. These one or more amphiphilic molecules along with the drug / API are dissolved together in one or more organic solvents. Examples of suitable organic solvents include, but are not limited to, acetone, methanol, ethanol, isopropyl alcohol, 1- 30 butanol, 2-butanol, 2-butanone, acetonitrile, carbon tetrachloride, chlorobenzene, diethyl ether, dimethyl ether, dimethylformamide (DMF), dimethyl sulfoxide (DMSO), ethyl acetate, chloromethane, and dichloromethane, wherein the selected solvent or mixture thereof facilitates a homogeneous coating formulation. In an embodiment, an organic solution comprising one or more amphiphilic 5 molecules and at least one drug / API is prepared by introducing a predetermined quantity of a composition containing said amphiphilic molecule(s) and said therapeutic agent(s) into an organic solvent. The resulting mixture is subjected to agitation and heating using a magnetic stirrer under controlled conditions, including a predetermined temperature and for a predetermined duration, sufficient to achieve 10 complete dissolution. Preparation of Aqueous Buffer Solution Subsequently, an aqueous buffer solution is prepared by dissolving one or more buffering agents in a predetermined volume of water to achieve a buffer solution of a specified molarity. The buffering agents may be selected from, but are not limited 15 to, acidic buffers, basic buffers, biological buffers, universal buffers, volatile buffers, and pharmaceutically acceptable buffers. Examples include phosphate- buffered saline (PBS), HEPES, Tris, MOPS, MES, PIPES, citrate buffer, acetate buffer, and carbonate buffer. Formation of Nanoencapsulation of Drug or API via Membrane Technology 20 In one embodiment, the nanoencapsulation of a drug or API is achieved by employing membrane technology under controlled laminar flow conditions. The dispersed phase and continuous phase are introduced into a membrane emulsification system, wherein the dispersed phase is directed through a precision- engineered porous stainless-steel membrane having pore diameters in the range of 25 about 20 nanometers to about 1000 nanometers. Under such controlled passage, the dispersed phase is seamlessly introduced into the continuous phase, facilitating the formation of nanoencapsulated drug / API entities. The process, as shown in Figure 1, illustrates the flow of continuous and dispersed phases through the stainless-steel membrane, where precision-engineered pores 30 (20–1000 nm) facilitate conversion of larger particles into nanosized particles, supporting the encapsulation process. Controlled laminar flow and simultaneous initiation, whereby, both, the continuous phase and the dispersed phase, start flowing into the membrane system at the same time during the encapsulation process. Both the phases contribute to the formation of high-quality nanoencapsulated drugs at the product outlet. 5 In another embodiment, the flow rates of the dispersed and continuous phases are controlled and may be varied depending on the desired particle size and distribution. Typical flow rate ratios include, but are not limited to, 1:2, 1:3, 2:1, 2:3, 3:1, and 3:2 of continuous phase to dispersed phase. By adjusting these flow ratios, the size of the resultant nanoparticles can be precisely tuned within the range of about 20 10 nanometers to about 500 nanometers as show in Figure 4: Dynamic Light Scattering (DLS) Chromatogram illustrates the high degree of control offered by the membrane-based technology in generating nanoparticles with uniform size distribution, precisely within the desired range. 15 In a further embodiment, the membrane-based emulsification step ensures high encapsulation efficiency, uniform particle size distribution, and enhanced stability of the nanoformulation. The process advantageously allows preparation of the nanoformulation within a short processing time, suitable for scalable industrial applications. 20 In yet another embodiment, the pore size of the membrane, flow rates, and ratio of continuous phase to dispersed phase may be selected in combination to achieve specific particle characteristics tailored to the intended pharmaceutical application, including, but not limited to, controlled release, targeted delivery, and improved 25 bioavailability. In still another embodiment, optional stabilizers, surfactants, or excipients may be incorporated into either the dispersed or continuous phase to enhance particle stability, prevent aggregation, and maintain integrity of the nanoencapsulated API 30 during storage and subsequent formulation. In a further embodiment, the process may be repeated iteratively or combined with additional post-processing steps to obtain the desired final form, concentration, and stability of the nanoformulation, without compromising encapsulation efficiency or particle uniformity. Such post-processing steps preferably include dialysis, 5 lyophilization, freezing, or sonication, alone or in combination. Post-Encapsulation Purification via Dialysis In one embodiment, the nanoencapsulated formulation obtained from the membrane system is subjected to dialysis to remove unencapsulated drug, free amphiphilic molecules, organic solvents, or other low-molecular-weight impurities. 10 Dialysis may be performed using conventional techniques including dialysis tubing, membranes, or cassettes with appropriate molecular weight cut-off (MWCO). The selection of dialysis media, membrane material, and dialysis duration may vary depending on the physicochemical properties of the encapsulated and non- encapsulated components. In certain embodiments, dialysis is performed for 15 approximately 6 to 12 hours. Freezing and Solidification In another embodiment, the purified nanoformulation may be subjected to freezing at controlled sub-zero temperatures, including but not limited to −40ௗ°C, −80ௗ°C, or rapid freezing using liquid nitrogen. 20 Lyophilization and Alternatives In yet another embodiment, the frozen nanoformulation may be subjected to lyophilization to obtain a dry, stable powder. Lyophilization may be performed under predetermined vacuum and controlled temperature conditions. Alternative drying techniques, including spray-drying, vacuum drying, or controlled solvent 25 removal, may also be employed. Sonication In a further embodiment, sonication may be applied to the purified or lyophilized nanoformulation by mixing it with one or more organic solvents, including but not limited to acetone, methanol, ethanol, isopropyl alcohol, 1-butanol, 2-butanol, 2- 30 butanone, acetonitrile, carbon tetrachloride, chlorobenzene, diethyl ether, dimethyl ether, DMF, DMSO, ethyl acetate, chloromethane, or dichloromethane. Sonication is performed at a predetermined frequency under controlled temperature to improve dispersion, achieve desired concentration, and enhance formulation stability. Combination of Post-Processing Steps In still another embodiment, two or more post-processing steps—including dialysis, 5 freezing, lyophilization or alternative drying, and sonication—may be combined in a sequential or iterative manner to optimize purity, stability, particle size, and reconstitution properties. Application onto Medical Devices In one embodiment, following the preparation of a nanoencapsulated drug solution 10 utilizing membrane-based technology, the resultant formulation is rendered suitable for application onto a medical device via a coating process. The said medical device can be selected from the group consisting of a stent, a balloon catheter, a stent mounted on a balloon, an implant, and a non-implantable medical device. In one of the embodiments, the advancement of the drug-coated balloons (DCB) of 15 the present invention provides an alternative, non-stent method for the percutaneous treatment of atherosclerotic lesions. Accordingly, the uniform and rapid transference of the drug upon inflation of the balloon at the target site, particularly the wall of the blood vessel or affected tissues, forms the basis of the drug-coated balloon rationale. Delivery of the drug to the 20 target site does not require any permanently implanted devices. The nanoencapsulated drug solution may be applied alone or in combination with one or more additional coating compositions comprising, but not limited to, polymeric layers, non-encapsulated drug layers, or other functional layers. Such 25 additional layers are not restricted to any specific material composition and may be configured to perform one or more roles, including, but not limited to, facilitating controlled, sustained, or rapid (burst) release of the active pharmaceutical ingredient at a target lesion site. 30 In another embodiment, the polymer layer may be configured to facilitate rapid release of the drug to the target lesion site within a matter of seconds while concurrently sustaining the presence of the drug at the site for a prolonged duration. In certain embodiments, a protective top layer may be disposed over the polymeric and / or nanoencapsulated drug layers. The concentration, chemical composition, and thickness of the protective layer may vary and are not intended to be limited to 5 any specific formulation or structural arrangement. In a further embodiment, the relative sequence and spatial arrangement of the layers disposed on the medical device may be adjusted or optimized depending upon the desired therapeutic outcome, including but not limited to enhanced drug penetration, controlled elution profiles, or minimized systemic distribution. 10 In yet another embodiment, the coating process may comprise one or more steps involving the sequential or simultaneous deposition of a polymer layer, a nanoencapsulated drug layer, and a protective top layer, wherein each of said layers may be applied using any suitable coating technique known in the art. Such 15 techniques may include, but are not limited to, dip-coating, spray-coating, electrospinning, or other physical or chemical deposition methods. Further, the protective topcoat layer is configured to dissolve or wash away at the lesion site, thereby exposing the underlying therapeutic layers. 20 In one embodiment, the nanoencapsulated drug formulation is sprayed directly onto the surface of the balloon to enhance bioavailability of the therapeutic agent at the lesion or treatment site. In another embodiment, the balloon substrate may be fabricated from a Nano11 copolymer or equivalent biocompatible polymeric material to further improve coating adherence, drug retention, or delivery 25 characteristics. Advantages of the invention: 1. Enables precise control over drug release kinetics, thereby enhancing the targeted delivery of the drug. 30 2. The coating process guarantees not only predictable and consistent drug release kinetics but also assures uniform therapeutic effects across the treated area, ultimately amplifying the treatment's overall efficacy and precision. 3. The design of the device aims for precise drug delivery, uniform distribution, and compatibility with the body 5 4. Increases bioavailability of the Drug at target site. 5. Elevates drug stability and solubility while achieving precise and targeted delivery to specific sites within blood vessels or affected tissues. 6. Membrane technology stands out for its ability to produce finely tuned particle sizes, opening new possibilities for applications that benefit from 10 such precision and uniformity. 7. The advancement of drug-coated balloons (DCB) presents an alternative non-stent method in the percutaneous treatment of atherosclerotic lesions. DCB has potential applications in the treatment of de novo lesions, in-stent restenosis (ISR), in peripheral artery disease (PAD) and coronary artery 15 disease (CAD). Examples It should be noted that the embodiments described herein are presented for illustrative purposes only and are not intended to limit the scope of the claimed invention. Variations, modifications, substitutions, and equivalents thereof will be 20 apparent to those skilled in the art and are considered to fall within the scope of the present disclosure. The invention will be better understood by reference to the following non-limiting examples. Example 1 Sr. Ingredients Function No. 1. Drug inhibit cell growth and blood vessel development, thereby preventing restenosis 2. DPPC- (1,2-Dipalmitoyl-sn- o It is a type of phospholipid glycero-3-phosphocholine) commonly used to create stable liposomes. o It also enhances encapsulation efficiency 3. Chol (Cholesterol o it is utilized in coating formulations as an emulsifying agent, enhancing stability, flexibility and water- absorbing properties. o It plays a vital role in liposome composition, contributing to rigidity and inhibiting lipid peroxidation 4. DSPE-PEG2000-(1,2-distearoyl- enhancing stability, entrapment sn-glycero-3- efficiency, and vesicle size control phosphoethanolamine-N- [amino(polyethylene glycol)- 2000]) 5. HEPES (4-(2-hydroxyethyl)-1- It provides buffering capacity, piperazineethanesulfonic acid) stabilizing pH levels, biocompatibility, solubility enhancement, and compatibility with other ingredients. 6. IPA-Isopropyl Alcohol Solvent or Vehicle Example 2 Sr. Ingredients Function No. 1. Everolimus inhibit cell growth and blood vessel development, thereby preventing restenosis 2. DPPC- (1,2-Dipalmitoyl-sn- o It is a type of phospholipid glycero-3-phosphocholine) commonly used to create stable liposomes. o It also enhances encapsulation efficiency 3. Chol (Cholesterol o it is utilized in coating formulations as an emulsifying agent, enhancing stability, flexibility and water- absorbing properties. o It plays a vital role in liposome composition, contributing to rigidity and inhibiting lipid peroxidation 4. DSPE-PEG2000-(1,2-distearoyl- enhancing stability, entrapment sn-glycero-3- efficiency, and vesicle size control phosphoethanolamine-N- [amino(polyethylene glycol)- 2000]) 5. HEPES (4-(2-hydroxyethyl)-1- It provides buffering capacity, piperazineethanesulfonic acid) stabilizing pH levels, biocompatibility, solubility enhancement, and compatibility with other ingredients. 6. IPA- Iso propyl Alcohol Solvent or Vehicle Example 3 Sr. Ingredients Function No. 1. Paclitaxel inhibit cell growth and blood vessel development, thereby preventing restenosis 2. DPPC- (1,2-Dipalmitoyl-sn- o It is a type of phospholipid glycero-3-phosphocholine) commonly used to create stable liposomes. o It also enhances encapsulation efficiency 3. Chol (Cholesterol o it is utilized in coating formulations as an emulsifying agent, enhancing stability, flexibility and water- absorbing properties. o It plays a vital role in liposome composition, contributing to rigidity and inhibiting lipid peroxidation 4. DSPE-PEG2000-(1,2-distearoyl- enhancing stability, entrapment sn-glycero-3- efficiency, and vesicle size control phosphoethanolamine-N- [amino(polyethylene glycol)- 2000]) 5. HEPES (4-(2-hydroxyethyl)-1- It provides buffering capacity, piperazineethanesulfonic acid) stabilizing pH levels, biocompatibility, solubility enhancement, and compatibility with other ingredients 6. IPA-Isopropyl Alcohol Solvent or Vehicle Example 4 Sr. Ingredients Function No. 1. Sirolimus inhibit cell growth and blood vessel development, thereby preventing restenosis 2. DPPC- (1,2-Dipalmitoyl-sn- o It is a type of phospholipid glycero-3-phosphocholine) commonly used to create stable liposomes. o It also enhances encapsulation efficiency 3. Chol (Cholesterol o it is utilized in coating formulations as an emulsifying agent, enhancing stability, flexibility and water- absorbing properties. o It plays a vital role in liposome composition, contributing to rigidity and inhibiting lipid peroxidation 4. DSPE-PEG2000-(1,2-distearoyl- enhancing stability, entrapment sn-glycero-3- efficiency, and vesicle size control phosphoethanolamine-N- [amino(polyethylene glycol)- 2000]) 5. HEPES (4-(2-hydroxyethyl)-1- It provides buffering capacity, piperazineethanesulfonic acid) stabilizing pH levels, biocompatibility, solubility enhancement, and compatibility with other ingredients 6. IPA-Isopropyl Alcohol Solvent or Vehicle Example 5: As depicted in Figures 5, 5.1, 5.2, 5.3, and 5.4, the coating formulation demonstrates a defined release profile. In particular: 5 ^ Figure 5.1 illustrates that at approximately 20 seconds post-application, a drug concentration of about 1.8 parts per million (ppm) is achieved, corresponding to approximately 7.91% cumulative release of the drug.^Figure 5.2 shows that at approximately 40 seconds, the drug concentration increases to approximately 6.98 ppm, correlating to a cumulative release of approximately 54.74%, indicative of an initial burst release phase. ^ Figure 5.3 shows a further increase in drug concentration to approximately 5 2.82 ppm, corresponding to a cumulative release of approximately 73.67%. ^ Figure 5.4 provides a comparative representation of the temporal release kinetics. ^ Figure 5 demonstrates the overall drug recovery profile from the coated medical device, highlighting both release dynamics and total bioavailability. 10

Claims

We Claim 1. A method for coating a medical device with a nanoencapsulated drug formulation utilizing membrane technology comprises the steps of: a. Preparing an organic solution containing one or more amphiphilic molecules and drug / API dissolved in an organic solvent; b. Preparing an aqueous buffer solution; c. Introducing the organic solution of Step a, as a dispersed phase through a precision-engineered porous stainless-steel membrane (20–1000 nm) into the aqueous buffer of Step b, as a continuous phase, under controlled laminar flow to obtain nanoparticles with an average size of 20–1000 nm, more preferably in range of 20-500nm; d. Subjecting the formulation of Step c, to dialysis, pre-freezing, and lyophilization to yield a dry stable powder; e. Reconstituting and diluting the powder of Step d, with organic solvent to prepare a sprayable solution; and f. Spraying the solution of Step e uniformly on the balloon surface.

2. The method as claimed in claim 1, optionally further comprises deposition of a polymer layers and / or protective topcoat layers over the coated medical device of Step f.

3. The method as claimed in claim 2, wherein the polymer layer and / or the nanoencapsulated layer is configured to facilitate a tailored release profile comprising an initial burst release followed by a sustained long-term release of the active agent.

4. The method as claimed in claim 2, wherein the polymer layer is adapted to release the active agent over an extended duration of approximately 30 to 90 days.

5. The method as claimed in claim 1, wherein the nanoencapsulation is achieved exclusively by membrane emulsification under laminar flow conditions and not by ultrasonic homogenization.

6. The method as claimed in claim 1, wherein the drug or active pharmaceutical ingredient is selected from the group consisting of sirolimus, everolimus, zotarolimus, tacrolimus, rapamycin, paclitaxel, and pharmaceutically acceptable salts, esters, or analogues thereof.

7. The method as claimed in claim 1, wherein the amphiphilic molecule is selected from the group consisting of phospholipids, sterols, PEGylated lipids, non-ionic surfactants, cationic lipids, and bile salts.

8. The method as claimed in claim 1, further comprising subjecting the nanoencapsulated formulation obtained from the membrane system to one or more post-encapsulation purification and stabilization steps, which include dialysis; freezing; lyophilisation.

9. The method as claimed in claim 8, wherein the method further comprises optionally subjecting the purified or lyophilized formulation to sonication, wherein the combination of dialysis, freezing, lyophilization, and / or sonication enhances formulation purity, stability, particle uniformity, and reconstitution characteristics.

10. A nanoencapsulated formulation prepared according to the method of claim 1, wherein the formulation comprises nanoparticles of a drug / API encapsulated within amphiphilic molecules.

11. The nanoencapsulated formulation as claimed in claim 10, wherein the nanoparticles exhibit a uniform particle size distribution ranging from aboutaverage diameter of 20 nanometers to about 1000 nanometers, more preferably in range of 20-500nm; 12. The nanoencapsulated formulation of as claimed in claim 10, wherein the formulation is devoid of polymeric reservoir matrices.

13. The nanoencapsulated formulation of claimed in claim 10, further comprising one or more pharmaceutically acceptable stabilizers, excipients, or surfactants configured to enhance nanoparticle stability, prevent aggregation, and maintain formulation integrity during storage and reconstitution.

14. A surface coated medical device, wherein the surface coating comprises a nanoencapsulated formulation according to claim 10.

15. The medical device as claimed in claim 14, wherein the surface coating comprises a multilayer structure including at least one polymer layer, at least one nanoencapsulated pharmaceutical formulation layer, and optionally at least one protective topcoat layer.

16. The medical device as claimed in claim 15, wherein the polymer layer provides sustained or controlled release of the drug / API.

17. The medical device as claimed in claim 15, wherein the protective topcoat layer is configured to dissolve or wash away at the lesion site, thereby exposing the underlying therapeutic layers.

18. The medical device as claimed in claim 15, wherein the surface coating provides both an initial burst release of drug / API and a sustained therapeutic release profile at the target lesion.

19. The medical device as claimed in claim 14, wherein the medical device is selected from the group consisting of a stent, a balloon catheter, a stent mounted on a balloon, an implant, and a non-implantable medical device.

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