Formulation and in-vitro release study of drug loaded liposomes for treating dry eye disease

• Main Author: Chua, Yan Ni
• Other Authors: Subramanian Venkatraman
• Format: Final Year Project
• Language: English
• Published: 2016
• Subjects: DRNTU::Engineering
• Online Access: http://hdl.handle.net/10356/66590
• Institution: Nanyang Technological University

Dry eye disease (DED) is a multifactorial condition resulting in discomfort, visual impairment and even tear film instability as a result of insufficient tear production or excessive tear evaporation. Dry eye disease is regarded as an economic burden as the patients incurred financial loss during the treatment of DED. Current DED treatments face difficulties in delivering drug effectively due to the poor drug penetration to the residing site as a result of the dynamic and static barriers in the eye. In addition, there is a need to also ensure a controlled release of drug in order to minimise drug toxicity which may lead to side effects in the body. In this project, we will be reporting the use of liposomal drug delivery system, to encapsulate the hydrophobic drug (Senicapoc) in its hydrophobic bilayer and aim to administer this formulation as an eye drop for the management of Dry Eye Disease (DED). The liposomal drug delivery system has been well discussed over the years and remains to be one of the most commonly used drug delivery system due to its’ natural biocompatibility with humans and low toxicity. In addition, such drug delivery system have been proven to provide numerous pharmaceutical benefits such as protecting the drugs within its bilayer as well as providing a sustained release of drugs. Thin film hydration method technology is employed to fabricate the liposomes and to encapsulate the drug within its hydrophobic bilayer of the liposomes. Extrusion was further performed to homogenise and to further reduce the liposome size to 80nm nanoparticles, achieving a good polydispersity index result. Nanoparticles are more preferred in eye application as the nanosize particles allow transparency and ease of penetration. Formulations will then be tested in vitro which includes release kinetics as well as the various stability studies of the formulation in terms of size and during loading. The degradation of free drug in the release medium will also be studies and discussed in this report. Formulations of 8 ± 0.4 mol% could be achieved and the release studies were performed in Phosphate Buffered Saline (PBS) of pH 7.4, at 37oC under the stirring of 50rpm to stimulate physiological conditions of the eye. Extraction method was used for sample collection daily and sink condition was maintained throughout the release study. Size and drug loading of liposomes were performed at specific intervals over a period of 28 days at both temperatures of 4oC and 37oC to study the stability of the formulation. Under the given conditions of 37oC under the stirring of 50rpm, it was experimentally determined that about 75% of the drug could be released in vitro within a period of 7 days. Moreover the size and drug loading of the liposomal formulation remained relatively stable with insignificant changes over a period of 28 days. The results of this study have shown the capability of utilising liposomal delivery system to achieve a controlled, sustained release of the drug hence achieving the primary objective of this project.