Liposomal and polymeric nanoparticles for targeted delivery of hydrophobic and hydrophilic drugs

Abstract

Diseases of modern life such as type II diabetes, cardiovascular diseases and cancer have a chronic inflammatory process at its base. The apparent link between such diseases and chronic inflammation can provide new modalities of chemotherapeutic interventions. Although treatment of chronic inflammation may not necessarily lead to a (complete) cure, it can act synergistically with other treatment modalities that are currently applied. Many different potent small drug molecules that can be of benefit in the treatment of inflammatory disorders have been identified. However, these established or potential drugs typically have a substantial set of adversary (side-) effects, especially upon chronic use. Therefore, it is of great importance to suppress and/or avoid such adverse effects as much as possible. A technology that has shown some promise in this regard has been the application of targeted nanomedicines, which can direct potent drug molecules away from certain tissues or cell types, while they also can accumulate locally within inflamed tissues or tumors. In the present thesis, the feasibility of applying lipid or polymer-based nanocarrier systems for the targeted (intracellular) delivery of small drug molecules has been demonstrated both in vitro and in vivo. Anti E-selectin, anti-VCAM-1 and anti-GD2 antibodies were coupled to the surface of the nanocarrier systems as targeting moieties. Several analyses, together with efficacy studies, have been carried out, including physicochemical characterization of the targeted nanomedicines and in vitro analysis of their binding to and internalization by activated endothelial cells or tumor cells. An in vivo pharmacokinetic pilot study was performed, evaluating immunoliposomes loaded with YM155. Collectively, the obtained results, demonstrated the suitability and potential of targeted nanomedicine formulations for further in vivo efficacy studies.