PUB096 Enhanced Delivery of Anticancer Drug to the Lungs via Liposomal Aerosols

Abstract

Lung cancer tends to spread very early, and is a very life threatening cancer and one of the most difficult cancers to treat. Non-small cell lung cancer (NSCLC) usually grows and spreads more slowly than small cell lung cancer. There are three forms of NSCLC: Adenocarcinomas are found in an outer area of the lung. Squamous cell carcinomas are usually found in the center of the lung by an air tube (bronchus). Large cell carcinomas can occur in any part of the lung. Liposomes were used as Effective encapsulation of both hydrophobic & hydrophilic molecules. Due to their ability to solubilize poorly water soluble drugs, facilitate their nebulization, minimizing clinical drug dose and reducing toxicity, prolonging and targeting release of therapeutic agents by modification of liposome surface. The failures of the present delivery systems are – Oral administration of etoposide at varying dosage for the treatment of lung cancer causes GI toxicity and disturbances of liver function. The parenteral administration of etoposide for lung cancer treatment has been reported to cause severe hepatic impairment and Hypotension. Moreover, intravenously injected ligands mediated liposomes have been limited due to - Leakage of their contents before they reach the target tissue, Rapid clearance from the blood stream, uptake by the macrophages of liver and spleen. Liposomes were prepared by lipid cast film method, optimized and then coupled with Mannose. Drug loaded Liposomes were characterized in-vitro for shape, size, and stability in various body fluids. The Air-jet nebulizer system was used for aerosol and was characterized for Appearance, Leak Test, Internal Pressure, Amount discharge/ actuation, Spray Pattern area and Penetration Efficiency. The in-vivo study comprised of estimation of serum and tissue distribution of drug and fluorescence microscopy. Liposomes formed were multilamellar and were found to be stable in gastric and intestinal fluids.Fluorescence microscopy suggested that liposomes were taken up by the gut associated lymphoid tissues and therapeutic level of drug can be achieved at desired site. Thus, from the results obtained it can be concluded that the Aerosolized mannose liposomes can deliver drug to the cancerous cells in an effective way and hold great potential for lung targeting. Through mannosylated liposomes, therapeutic level of drug can be achieved at desired site. The system carried dual function, firstly retention of drug and secondly selective delivery of etoposide to lungs.