Biomaterial-based targeted particulate drug carriers: biophysical properties, cell-particle interactions and therapeutic responses
Our efforts in the drug delivery arena focus on three drug delivery technologies that are inventions of our group. All are based on biomaterials, and can form vesicular-shaped particles. The particles of one technology are named Bioadhesive Liposomes (BALs), consisting of regular liposomes – hence their shell is a lipid bilayer membrane. Surface-modification by covalent binding of target-recognition agents such as hyaluronan, collagen, EGF or gelatin to the liposomal surface, renders them bioadhesive. The particles of the second technology are named gagomers (GAGs), their shell is made of hyaluronan, and their interior contains water and lipids. The particles of the third technology are named collagomers, their shell is made of collagen and their interior from collagen-lipid conjugates. The goal is to apply these particles as drug carriers for the treatment of pathologies such as tumors, infectious diseases, diabetes and inflammatory diseases, in order to improve deficiencies of treatment with free drugs, as the latter lead to poor therapeutic responses and to treatment failures. The choice of more than one carrier technology allows for the match of carrier species, size and route of administration that best-fits the designated therapy. Our conceptual approach, for any project, is to start at the molecular level and proceed systematically to studies in cell cultures, and then to animal studies. At the molecular level we investigate structural, physicochemical and biochemical properties of the drug-carrier systems selected for a given task. In cell cultures we explore cell–carrier interactions with particular emphasis on: kinetics and thermodynamics of cell-carrier binding, cellular localizations of carrier and drug, the mechanisms by which carrier-mediation affects drug entry into cells, and therapeutic activity. The in vivo studies focus on pharmacokinetics, drug and carrier biodistributions, adverse effects, and therapeutic responses.
Drug delivery to tumor cells mediated by targeted nano carriers. Left-hand side: Bioadhesive Liposomes bound to mouse melanoma cells. Drug load (fluorescein, green fluorescence) is localized at the cell membrane. Right-hand side: Gagomers (red fluorescence) bound to mouse leukemia cells. Drug load (doxorubicin, red fluorescence) is localized inside the cell.