LIPOSOMAL APPROACH TO PHARMACEUTICS

Efficient and safe drug delivery has always been a challenge in therapy and diagnostics. The use of nanotechnology, as well as the development of nanocarriers for drug delivery, received great attention according to the evidence that they can theoretically act as “magic bullets” capable to hit the target cells while sparing normal tissues and organs. Liposomes are suitable as carriers of both hydrophilic and lipophilic drugs and are able to deliver drugs to the target site. The vesicle properties are specifically dictated by size, shape, and surface chemistry which are able to modify the intrinsic pharmacokinetics of the drug and, eventually, the drug targeting to the pathological areas. Liposomes can be developed in different approach to pharmaceutics. According to this, in our laboratory, liposomes have been proposed as biomembrane model in order to study the interaction between surfactant vesicles and liposomes, since it is very difficult to directly observe the membrane fusion due to the complexity of biomembranes and the high speed of the process (1). Furthermore our research involves the “classic” use of liposomes as drug delivery systems. For example they have been studied to obtain an efficient brain delivery of prodrugs to enhance the extracellular levels of L-Dopa and Dopamine in rat striatum of freely moving rat (2). Maleic and fumaric diamides of (O,O-diacetyl)- L-Dopa-methylester, synthesized in order to attenuate marked fluctuations of L-Dopa plasma levels and to overcome the problem of low bioavailability of L-Dopa, have been entrapped in liposomal formulations to obtain chemical stability in aqueous buffer solutions, slow release of LD in human plasma and sustained delivery of Dopamine in rat striatal dialysate (3). With the aim to provide a protection against chemical degradation and enzymatic metabolism and, consequently, to get a high prodrug quantity able to cross the Blood Brain Barrier, liposomal formulations of 2-amino-N-[2-(3,4-dihydroxy-phenyl)-ethyl]-3-phenyl-propionamide (DOPH) were prepared and characterized (4). Polysaccharide-coated liposomes have been proposed as carrier of peptide drug by the oral route because they are able to minimize the disruptive influences on peptide drugs of gastrointestinal fluids. In particular, a modified polysaccharide, O-palmitoylscleroglucan (PSCG), was synthesized and used to coat unilamellar liposomes for oral delivery of Leuprolide, a synthetic superpotent agonist of luteinizing hormone releasing hormone receptor (5). In collaboration with the Centre for Surgical Technologies at the Faculty of Medicine of the Katholieke Universiteit of Leuven (Belgium), thermosensitive liposomes have been prepared to deliver the Cytotoxic Necrotizing Factor 1 (CNF-1) toward lung tissues, with an effective approach against the Congenital Diaphragmatic Hernia (CDH). These carriers are able to release drugs/proteins due to the hyperthermia, as a consequence of lung tissues inflammation. The preliminary studies have shown the safety of these structures in foetal rats and rabbits with CDH. Finally, in our laboratory, the phospholipidic shell was used to prepare novel nanobbubles, NBs (6) - ). These structures can act as theranostic agents. The preclinical experiments, developed in collaboration with the Queens Medical Research Institute at the University of Edinburgh, were carried out to demonstrate that ultrasound-mediated NBs destruction has the potential to open the BBB tight junctions and trigger therapeutic agent deposition in the brain. The results are very promising and suggest the possible use of NBs in the theranostic fields.