Diabetes treatment drug encapsulation and release study

• Main Author: Tendi, Jessica Kim
• Other Authors: Loo Say Chye Joachim
• Format: Final Year Project
• Language: English
• Published: 2015
• Subjects: DRNTU::Engineering::Materials::Biomaterials
• Online Access: http://hdl.handle.net/10356/62558
• Institution: Nanyang Technological University

Diabetes is a long-term disease suffered by many people worldwide and it has caused 4.9 million deaths in 2014 [1]. The transplantation of pancreatic islet cells into the anterior chamber of the eye (ACE) is a recent development which has shown potential as an emerging treatment among the various treatments currently available [2] [3]. In this study, tolbutamide, a first-generation sulfonylurea drug, was encapsulated in degradable polymeric microparticles to promote insulin production of transplanted islet cells in ACE. An immunosuppressive drug, rapamycin, was also encapsulated to prevent the grafted islet cells from being attacked by the host’s immune response. This project aims to encapsulate the two drugs mentioned into microparticles using oil-in-water emulsion solvent evaporation fabrication technique, and eventually to have in vitro sustained release study. A quantification method using HPLC for tolbutamide dissolved in ACN was created in this project. The mobile phase used was ACN/H2O (15:85) combined with 0.05% TEA. TEA was used to reduce fronting peaks and to stabilize the peaks’ symmetrical shape. However, the method did not give consistent results and needs to be improved. Rapamycin-loaded PCL and PCL:PLGA (2:1) blend microparticles achieved sustained release over a period of 30 days in vitro studies. In contrast, PLGA microparticles did not show any drug release. PCL is in its rubbery state at 37°C as it has a Tg of -60°C. Because of PCL’s high degree of movement, water may easily penetrate through the polymer matrix. This may have led to the higher release rate of rapamycin from PCL and PCL:PLGA (2:1) blend microparticles. Rapamycin sustained release profile will be useful in tolbutamide’s in vitro sustained release study. With more tuning on the drug release profiles, the project can be brought into in vivo studies in preparation of clinical studies.