Hydrogel Technology
Toleogenics ImmunoGel technology
Toleogenics ImmunoGel technology
Tolerogenics S.à.r.l. is using an innovative hydrogel technology for sustained drug delivery for a time period that is sufficient for efficient tolerogenic priming of immune cells. The hydrogelpolymer is an application-tailored PLGA-PEG-PLGA triblock polymer. The proprietary synthesis procedure of Tolerogenics S.à.r.l. allows to define the gelation temperature and release characteristics of the hydrogel polymer.
The polymer molecule exhibits a hydrophilic core region and hydrophibic ends. A aqeous solution of this polymer is reverse thermosensitive, meaning it is fluid and injectable at room temperature and will rapidely form a hydrogel at body temperature (e.g. after subcutaneous injection).
This behavior is based and a shift in structural conformation in solution. At room temperature the preferred structure are micelles, hiding the hydrophobic parts from the solvent. When the temperature raises the micelles get instable and the polymer molecule start forming an connecting network, thereby generating a solid hydrogel.
The polymer is biodegradable due to the instability of ester-bonds in the aqueous physiological environment. This process continues at slow rate and will eliminate the hydrogel from the body in several weeks in a non-toxic way.
The hydrogel is used as advanced drug delivery vehicle.
The polymer solution is fluid at room temperature and can be mixed with active components and applied by subcutaneous injection. After injection the polymer rapidely turns into a solid hydrogel at body temperature, forming an advanced drug delivery depot.
Targets of this therapy approach are peripheral antigen-presenting cells (APC) of skin including macrophages, dermal dendritic cells and Langerhans cells.
These cells are modulated by the active components of the hydrogel (e.g. peptide loaded PS-liposomes) to act as tolerogenic cells, capable of inducing antigen-specific tolerance in T cells, turning naive or even differentiated T cells into regulatory T cells.
From the hydrogel depot small molecules are released mainly by diffusion. The result is a controlled drug release with an early burst phase for smaller molecules. It allows to quickly build up a concentration gradient of “find-me” signal molecules (e.g. ATP) to attract antigen-presenting cells, like macrophages and dendritic cells to the hydrogel site.
Hydrogel embedded larger molecules (e.g. PS-liposomes) are mainly released by biodegradation of the hydrogel. This results in a delayed release of larger molecules over a defined time period of approximately 3-4 days.
The sustained release of larger active substances provides an effective interaction with the immune cells and induction of tolerance in peripheral dendritic cells of the skin.
For the therapeutic approach of Tolerogenics, a sustained release for a time period of 2-3 days is important since the development of immunologic memory requires the engagement of a T cell receptor over 12-48 h and long-lasting memory may even require repetitive exposure.
The tolerogenic dendritic cells will migrate to the lymphatic system and interact with T cells to generate allergen-specific regulatory T cells (Tregs). These Tregs have been shown to be able to regulate the immune system and are capable to control the harmful immune condition and to cure the immune disease.
More Information?
You would like to get more information about Tolerogenics key technologies? Please click here for the technology overview or here to contact us.