Fabrication, Characterization, Co-Localization And Imaging Of Drug Loaded Biodegradable Plga Microparticles On Microarray Platforms

Date(s) - 03/03/2014
10:00 am

Nikunj Agrawal

Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disease occurring in the pancreatic islets and accounts for diabetes in children and adolescents. T1DM is associated with pathogenic action of self –reactive effector T cells (Teffs) on the β cells. However, several recent studies have shown that the disease pathology is also attributed to a second T cell subset, known as regulatory T Cells (Tregs), which plays a critical role in the development of T1DM. Newer therapeutic approaches try to maintain the homeostatic balance between Teff and Treg cells in patient affected with T1DM. Of particular interest to our research group is DC based immunotherapy approach where we aim to utilize the tolerogenic potential of DCs as therapeutic agents for autoimmune diseases and transplant rejection.  

A number of biological and pharmaceutical agents, including IL-10, thymic stromal lymphopoietin (TSLP), and transforming growth factor (TGF-β) have been reported to promote DCs with capacity to instigate CD25+ T cell proliferation and differentiation from CD25- T cells. Therefore, our lab is interested in investigating the induction of tolerogenic DCs via use of several drugs of interest (Aspirin, Curcumin, Epigallocatechin gallate, Menadione, Ergosterol, TGF Beta) which will help in increasing the levels of tolerogenic signaling, thereby inducing production of Tregs. Suppression of effector T cells is accomplished by the ability of Tregs to impair antigen presentation by mature DCs. Thus, the crucial step in Treg-mediated immuno-suppression is generation of Tregs which can be initiated by tolerogenic DC.

One way to facilitate the investigation of small molecules and their potential in up regulating the tolerogenic DC subset is by synthesizing drug loaded biodegradable microparticles and investigating them in a high throughput manner. Screening of immune cell response towards these microparticle based vaccines on a micro-array platform is therefore of interest to our group.

Microarray technology has emerged as a valuable tool in biological sciences, particularly for high-throughput applications. Furthermore, it helps in economical savings by using smaller volume of expensive reagents, high throughput analysis of data, portability and waste reduction as compared to conventional biological assays technique of using traditional 12/24/96/384 multi-well plates. This further leads to one of the long envisioned and now approaching reality of personalized medicine or personalized healthcare where better treatment can be offered to individuals based on their responding behavior rather than the name of the disease they are suffering from.

Today, commercially available arrays are available which provide application specific, miniaturized assays. Miniaturization techniques are an expanding field of research and have great potential in a field of single cell line analysis. Microwell and microarrays have successfully been able to acquire data for statistically significant results.