NANO THERAPEUTIC APPROACHES FOR THE TREATMENT AND MANAGEMENT OF VARICOSE VEINS

Abstract

Varicose veins, a subgroup of peripheral cardiovascular diseases, predominantly afflict the lower extremities and pose substantial challenges in both diagnosis and treatment due to their complex and multifaceted etiology. The development of varicose veins is driven by a combination of hormonal, environmental, and molecular factors. This highlights the necessity for advanced diagnostic methods and innovative therapeutic approaches to enhance patient outcomes. A comprehensive understanding of varicose veins requires an in-depth exploration of their epidemiology, pathophysiology, and diagnostic methods, such as duplex ultrasonography and factor-based classification systems. The effectiveness of current diagnostic tools in detecting chronic venous diseases must be thoroughly evaluated. Emerging therapies, such as sclerotherapy and endovenous thermal ablation, show promising outcomes but come with economic challenges and concerns regarding patient compliance. Studies on venous wall remodelling and inflammatory pathways emphasize the importance of precise diagnostic tools and tailored therapeutic approaches. However, nanotechnology holds significant potential for revolutionizing the diagnosis and treatment of varicose veins, paving the way for more effective and targeted interventions. Although nanotherapeutics hold great promise for treating varicose veins, the development of these advanced treatments encounters several substantial challenges. The principal challenges encompass the lack of validated animal models and an insufficient body of literature specifically focused on the application of nanoparticles for the treatment of this condition. The thesis details the development of an innovative nano-carrier system specifically designed to overcome these challenges and effectively mitigate the progression of varicose veins. The development of drug-induced animal models for varicose veins is a crucial step in understanding the condition and evaluating potential therapies. This phase focused on addressing the inherent challenges and side effects associated with the drugs used to induce the condition. Subsequently, the focus shifted to designing and optimizing a nano-carrier system specifically aimed at targeting varicose veins. Firstly, developing a varicose vein model in Wistar rats using niacin and amphotericin B was established. Due to the significant challenges posed by the side effects of amphotericin B, such as dilated cardiomyopathy and severe nephrotoxicity, we sought innovative solutions to mitigate these issues. Utilizing the ionic gelation method, we created mucomimetic and ix biocompatible carboxymethyl tamarind seed polysaccharide (CMTSP) nanoparticles. This approach not only addressed the adverse effects associated with amphotericin B but also presents a promising pathway for effective and targeted treatment of varicose veins. We subsequently developed niacin-loaded polymeric films (NLPFs) and lyotropic liquid crystal nanoparticles (NLCS) to tackle niacin-induced cutaneous flushing, which presented an additional challenge in establishing drug-induced varicose vein models. The NLPFs demonstrated a slow and sustained drug release profile, along with high biocompatibility, making them suitable for extended therapeutic use. Meanwhile, the NLCS improved therapeutic outcomes by reducing hepatotoxicity and alleviating flushing. This reduction in flushing was achieved by lowering prostaglandin (PGD) levels, which are known to contribute to this adverse effect. Finally, we developed molsidomine-loaded liquid crystal nanoparticles (MD-LCNPs) for the treatment of varicose veins. The formulations significantly alleviated varicose vein symptoms, with levels of reactive oxygen species (ROS) and nitric oxide (NO) returning to normal compared to control groups. Histopathological and haematological examinations confirmed the formulation's biocompatibility, revealing no significant toxicity in the blood or vital organs. Additionally, our findings demonstrated that the treatment groups showed normalized levels of key molecular markers, including VEGF, PDG2/E2, ICAM-1, and VCAM-1, as assessed by ELISA. These results indicate that MD-LCNPs are an effective and biocompatible option for treating varicose veins by modulating essential molecular pathways associated with the condition. Overall, the thesis represents a comprehensive effort, encompassing the development of animal models and the exploration of potential drug side effects through nanotechnology to create a novel therapy aimed at enhancing varicose vein management.