Formulation and in vitro release study of drug loaded liposomes for peripheral artery disease

• Main Author: Welly, Seisilya
• Other Authors: Subramanian Venkatraman
• Format: Final Year Project
• Language: English
• Published: 2016
• Subjects: DRNTU::Engineering
• Online Access: http://hdl.handle.net/10356/66592
• Institution: Nanyang Technological University

The current treatments for Peripheral Artery Disease (PAD) generally lead to restenosis at the site of intervention, with only 33% of the patients have a patent artery one year after procedure. The use of anti-proliferative drugs, such as Paclitaxel (PTX) and Sirolimus, have been demonstrated to be successful in the treatment of restenosis in the coronary artery. However, limited success was reflected in the case of PAD. This is due to the higher probability of calcification and longer area of blockage in the peripheral artery as compared to that in the coronary artery. Being inspired by the properties of liposomes as a drug delivery carrier to release therapeutic agents sustainably, this project aims to encapsulate PTX and Sirolimus in liposomes to prevent restenosis after angioplasty procedure in PAD. Two types of lipids, namely egg phosphatidylcholine (EPC) and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) were used to encapsulate 5 mole % of PTX. In vitro release from both formulations, as well as their liposomes size and encapsulated drug stability over the time, were characterized. Results show that PTX could be released sustainably, with negligible burst release. However, EPC formulation possessed faster release characteristics compared to POPC formulation. The encapsulated PTX in both formulations was stable at 4 oC throughout the study. As for liposomes size, POPC formulation was much more stable as compared to EPC formulation. For Sirolimus, 7.6 mole % of Sirolimus was loaded into EPC liposome and in vitro release, size and drug stability were determined. In vitro release of Sirolimus showed 30% of burst release at the first 3 hour, followed by sustained releasing of the drug in the next 28 days. Sirolimus formulation shows better drug and size stability while stored in 4 oC than that in 37 oC. In conclusion, PTX and Sirolimus have been successfully encapsulated into liposomes and sustained release of both drugs were achieved. All the formulations demonstrated good stability in terms of liposomes size and drug stability at 4 oC for at least one month. These formulations would be useful in reducing restenosis and their efficacy will be determined in vivo in the future study.