Development of a Glucose-Triggered Drug Delivery Device Using Liposomes and Poly (2-ethyl acrylic acid)

Sorada Kanokpanont¹ and Margaret A. Wheatley^1,2
1School of Biomedical Engineering
²Science and Health System
Drexel University
Philadephia, PA  19104
sorada@drexel.edu
(215) 895-5831

The current study is the development a self-regulated, glucose responsive insulin delivery system, using liposomes, pH sensitive polymer, and the help of the feed back reaction of glucose oxidase enzyme. The proposed system composed of liposome c ontaining insulin, pH-sensitive polymer, and glucose oxidase enzyme (GO) all entrapped in a microcapsule. In the presence of high levels of glucose, gluconic acid is produced at the GO. This results in the reduction of the capsule internal pH, triggerin g the pH-controlled conformational change of the polymer, which results in the polymer-liposome interaction and induces the release of the drug.

Poly (2-ethylacrylic acid)(PEAA) has the ability to interact with and rearrange the bilayer of phospholipid liposomes at low pH. The previous studies in the interaction of unencapsulated liposomes PEAA show the ability of PEAA to induce the release of Dio leoylphosphatidylcholine (DOPC) liposome contents at pH lower than 6.8. The rate and extent of release is controllable by the pH and the PEAA concentration. The release can be switched on again, reflecting the pulsed-release ability of the system. The next step of the development for this insulin delivery system is to put the PEAA and liposomes to work inside the suitable microcapsule in response to the glucose level of the environment.

The system was tested in the alginate microcapsules with different cationic coating materials. The pH reduction due to GO reaction show a promising results to use GO as a glucose sensor. The pH of the solution composed of 29.85 mg/ml GO reduced 2.5 unit when 3.226 mg/ml of glucose (diabetes blood glucose level) was added where at the low blood glu cose level (0.3226 mg/ml) the pH reduction was less than 0.5 unit from the original pH (7.2). In order to complete the creation of the this insulin delivery system, the further research plans are proposed in finding the suitable microcapsule, immobilizin g of the GO, combining the use of encapsulated liposomes and PEAA with immobilized GO, using insulin as the entrapped species instead of the fluorescence probes, and optimization of the in vitro insulin release.