The advent of the drug eluting stent (DES) has changed the management of coronary vessel revascularization very effectively. However, a DES imposes risk of long-term adverse clinical events such as inadequate vascular endothelization, inflammatory response, and stent thrombosis. A drug coated balloon offers advantages of deploying antiproliferative drugs at blocked lesions while eliminating the long-term risk associated with drug eluting stents. The major mechanism of drug delivery from this coated balloon involves adsorption of drug particles on inner lumen of coronary artery upon balloon expansion after which drug diffuses to the inner layers due to the concentration gradient. The major challenges in engineering such drug delivery devices are (1) to retain majority amount of drug on balloon during tracking and (2) program faster drug delivery within shorter exposure time. In the current research work, we have adopted different drug coating methods such as dip coating, brush coating, coating with ultrasonic atomization, and coating with air brush spray method to coat nanoparticles of Sirolimus drug encapsulated in phospholipids. For each of the methods, samples were studied for drug loading, coating integrity, and release characteristics of the Sirolimus coated balloon. An arterial path was simulated to measure the amount of drug loss during navigation and tracking. Drug release was measured for each of the coated system in phosphated buffer saline (PBS) solution of pH 7.4 and in Hank's solution of 7.4 pH at 37 degrees C at different time intervals. Also, the sample surface was analyzed for coating integrity after coating, after tracking, and after drug release. The resultant surface characteristics were correlated to the stages of balloon coating, tracking, and drug release, respectively. Among the different coating techniques employed, the method that was best in terms of coating durability and release effectiveness was further investigated for the drug release mechanism using available mathematical models. The analyses of drug loading on balloon surfaces and drug release from balloon surfaces were evaluated with the help of different statistical techniques. It is found that release of drug was not purely under influence of diffusion but mechanical abrasion during balloon expansion also played vital role.