Despite functional evidence for acid sensitive bond cleavage of dendritic polyglycerol drug-conjugates in cellular compartments, the mechanistic details pertaining to such process (e.g. kinetics and sites of cleavage) remain unexplored. To address these questions directly, we are working on the synthesis of a novel FRET-based polymer conjugates that changes its fluorescence upon drug release. Fluorescence analysis of the first conjugates revealed that pH dependent bond cleavage can be measured by fluorescence spectrophotometry at endosomal and lysosomal pHs. A new approach would be the introduction of targeting moieties (e.g. peptides, antibodies) to improve selectivity to specified tissue or sites.
We have established a platform technology for PEGylated nanoparticles based on dendritic polyglycerol. The design of this multifunctional approach allowed to fine-tune the drug-polymer conjugates with respect to drug loading and molecular weight and to prepare macromolecular prodrugs with similar surface charge and diameter, with different drugs and drug loading ratios as well as combination therapeutics that enable the release of at least two drugs. Furthermore, the multifunctional drug delivery system can easily be adapted to incorporate targeting ligands and diagnostic probes.
The combination of nanogel properties and thermo-responsiveness generates a promising candidate for the development of smart nanocarrier systems, which can be influenced by temperature with high responsiveness, reveal high loading capacity, can improve drug stability, and thus can be used for stimuli-controlled release in drug delivery. Our hypothesis treats the preparation of a new thermo-responsive glycerol based nanogel system and the investigation of their phase behavior with respect to potential biomedical applications. Initial focus was given to fabricate nanogels with size control over the range of 50 - 400 nm and narrow size distributions.
Successful gene therapy relies on a rational design approach which considers the distinctive structural requirements that are necessary to create an efficient and safe gene carrier. Cationic lipids, polymers, and dendrimers are among the most promising synthetic non-viral vectors so far. Combination of their essential features led to the realization of hybrid systems for prospective use as gene vehicles.